Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four R...Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.展开更多
Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug r...Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.展开更多
BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.Th...BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.展开更多
Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objectiv...Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).展开更多
BACKGROUND Extramedullary multiple myeloma(MM)(EMM)is a rare and aggressive subentity of MM that can be present at diagnosis or develop anytime during the disease course.There is a paucity of data on the clinical char...BACKGROUND Extramedullary multiple myeloma(MM)(EMM)is a rare and aggressive subentity of MM that can be present at diagnosis or develop anytime during the disease course.There is a paucity of data on the clinical characteristics and overall epidemiology of EMM.Furthermore,there is a scarcity of data on how the interaction of age and gender influences the survival of EMM.AIM To evaluate the clinical characteristics of patients with EMM over the past 2 decades and to identify epidemiologic characteristics that may impact overall prognosis.METHODS A total of 858 patients diagnosed with EMM,between 2000 and 2017,were ultimately enrolled in our study by retrieving the Surveillance,Epidemiology,and End Results database.We analyzed demographics,clinical characteristics,and overall mortality(OM)as well as cancer-specific mortality(CSM)of EMM.Variables with a P value<0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors,with a hazard ratio(HR)of greater than 1 representing adverse prognostic factors.RESULTS From a sample of 858 EMM,the male gender(63.25%),age range 60-79 years(51.05%),and non-Hispanic whites(66.78%)were the most represented.Central Nervous System and the vertebral column was the most affected site(33.10%).Crude analysis revealed higher OM in the age group 80+[HR=6.951,95%confidence interval(95%CI):3.299-14.647,P=0],Non-Hispanic Black population(HR=1.339,95%CI:1.02-1.759,P=0.036),Bones not otherwise specified(NOS)(HR=1.74,95%CI:1.043-2.902,P=0.034),and widowed individuals(HR=2.107,95%CI:1.511-2.938,P=0).Skin involvement(HR=0.241,95%CI:0.06-0.974,P=0.046)and a yearly income of$75000+(HR=0.259,95%CI:0.125-0.538,P=0)had the lowest OM in the crude analysis.Crude analysis revealed higher CSM in the age group 80+,Non-Hispanic Black,Bones NOS,and widowed.Multivariate cox proportional hazard regression analyses only revealed higher OM in the age group 80+(HR=9.792,95%CI:4.403-21.774,P=0)and widowed individuals(HR=1.609,95%CI:1.101-2.35,P=0.014).Multivariate cox proportional hazard regression analyses of CSM also revealed higher mortality of the same groups.Eyes,mouth,and ENT involvement had the lowest CSM in the multivariate analysis.There was no interaction between age and gender in the adjusted analysis for OM and CSM.CONCLUSION EMM is a rare entity.To our knowledge,there is a scarcity of data on the clinical characteristics and prognosis factors of patients with extramedullary multiple myeloma.In this retrospective cohort,using a United States-based population,we found that age,marital status,and tumor site were independent prognostic factors.Furthermore,we found that age and gender did not interact to influence the mortality of patients with EMM.展开更多
Introduction Multiple myeloma(MM),characterized by the proliferation of monoclonal plasma cells in the bone marrow,has the second highest incidence among hematologic malignancies1.Because of its incurable nature,treat...Introduction Multiple myeloma(MM),characterized by the proliferation of monoclonal plasma cells in the bone marrow,has the second highest incidence among hematologic malignancies1.Because of its incurable nature,treatments for MM are aimed primarily at obtaining minimal residual disease(MRD)negativity and achieving persistent control,both of which are believed to be important strategies to prolong survival and improve prognosis in patients with MM.展开更多
Objective:Metabolic disorders are regarded as hallmarks of multiple myeloma(MM)and are responsible for rapid cancer cell proliferation and tumor growth.However,the exact biological roles of metabolites in MM cells hav...Objective:Metabolic disorders are regarded as hallmarks of multiple myeloma(MM)and are responsible for rapid cancer cell proliferation and tumor growth.However,the exact biological roles of metabolites in MM cells have not been fully explored.This study aimed to explore the feasibility and clinical significance of lactate for MM and investigate the molecular mechanism of lactic acid(Lac)in the proliferation of myeloma cells and cell sensitivity to bortezomib(BTZ).Methods:Metabolomic analysis of the serum was carried out to obtain metabolites expression and clinical characteristics in MM patients.The CCK8 assay and flow cytometry were used to detect cell proliferation,apoptosis,and cell cycle changes.Western blotting was used to detect the potential mechanism and apoptosis-and cycle-related protein changes.Results:Lactate was highly expressed in both the peripheral blood and bone marrow of MM patients.It was significantly correlated with Durie-Salmon Staging(DS Staging)and the International Staging System(ISS Staging)and the serum and urinary involved/uninvolved free light chain ratios.Patients with relatively high lactate levels had a poor treatment response.Moreover,in vitro experiments showed that Lac could promote the proliferation of tumor cells and decrease the proportion of G0/G1-phase cells,which was accompanied by an increased proportion of S-phase cells.In addition,Lac could decrease tumor sensitivity to BTZ by disrupting the expression of nuclear factor kappa B subunit 2(NFκB2)and Re1B.Conclusion:Metabolic changes are important in MM cell proliferation and treatment response;lactate could be used as a biomarker in MM and as a therapeutic target to overcome cell resistance to BTZ.展开更多
Novel drug availability has increased the depth of response and revolutionised the outcomes of multiple myeloma patients.Minimal residual disease evaluation is a surrogate for progression-free survival and overall sur...Novel drug availability has increased the depth of response and revolutionised the outcomes of multiple myeloma patients.Minimal residual disease evaluation is a surrogate for progression-free survival and overall survival and has become widely used not-only in clinical trials but also in daily patient management.Bone marrow aspiration is the gold standard for response evaluation,but due to the patchy nature of myeloma,false negatives are possible.Liquid biopsy and blood-based minimal residual disease evaluation consider circulating plasma cells,mass spectrometry or circulating tumour DNA.This approach is less invasive,can provide a more comprehensive picture of the disease and could become the future of response evaluation in multiple myeloma patients.展开更多
Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,a...Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,and specifically BM mesenchymal stem cells(BM-MSCs),has a key role in the pathophysiology of this disease.Multiple data support the idea that BM-MSCs not only enhance the proliferation and survival of MM cells but are also involved in the resistance of MM cells to certain drugs,aiding the progression of this hematological tumor.The relation of MM cells with the resident BM-MSCs is a two-way interaction.MM modulate the behavior of BM-MSCs altering their expression profile,proliferation rate,osteogenic potential,and expression of senescence markers.In turn,modified BM-MSCs can produce a set of cytokines that would modulate the BM microenvironment to favor disease progression.The interaction between MM cells and BM-MSCs can be mediated by the secretion of a variety of soluble factors and extracellular vesicles carrying microRNAs,long non-coding RNAs or other molecules.However,the communication between these two types of cells could also involve a direct physical interaction through adhesion molecules or tunneling nanotubes.Thus,understanding the way this communication works and developing strategies to interfere in the process,would preclude the expansion of the MM cells and might offer alternative treatments for this incurable disease.展开更多
BACKGROUND The treatment of multiple myeloma has significantly progressed over the past half-century.The purpose of this study was to perform a systematic review and meta-analysis in order to explore the efficacy and ...BACKGROUND The treatment of multiple myeloma has significantly progressed over the past half-century.The purpose of this study was to perform a systematic review and meta-analysis in order to explore the efficacy and safety of daratumumab in treating multiple myeloma.AIM To explore the efficacy and safety of daratumumab in treating multiple myeloma.METHODS A systematic literature search was performed using Chinese and English databases,including the China National Knowledge Infrastructure,Wanfang,China Biology Medicine,VIP,the Cochrane Library,Embase,and PubMed.The search encompassed studies in treating multiple myeloma with daratumumab,spanning from the inception of the database to June 2023.Revman 5.1 software was used for analysis.RESULTS Our analysis included eight English articles and one Chinese article of high quality.The meta-analysis results indicated that compared to other therapies,daratumumab could improve the overall response rate(ORR)[odds ratio(OR)=2.67,95%confidence interval(CI)=2.01,3.53,Z=6.85,P<0.00001],complete remission(CR)(OR=2.87,95%CI=2.16,3.83,Z=7.23,P<0.00001)and progression-free survival(PFS)time(hazard ratio=0.48,95%CI=0.38,0.60,Z=6.54,P<0.00001)in patients with multiple myeloma.These differences were statistically significant.Additionally,these results suggested that daratumumab increases the risk of neutropenia and thrombocytopenia with minimal effect on the incidences of anemia and upper respiratory tract infections.CONCLUSION Daratumumab can improve ORR,CR rate,and PFS in patients with multiple myeloma.It also increases the risk of neutropenia and thrombocytopenia,necessitating careful monitoring during its clinical application.展开更多
Background: Osteoporosis (OP) is a common clinical manifestation of multiple myeloma (MM). The aim of this study was to investigate the possible molecular pathways and shared genes in the co-occurrence of OP and MM. M...Background: Osteoporosis (OP) is a common clinical manifestation of multiple myeloma (MM). The aim of this study was to investigate the possible molecular pathways and shared genes in the co-occurrence of OP and MM. Methods: The Gene Expression Omnibus database was used to retrieve gene expression information. Use WGCNA and differential analysis to screen out Hub genes. The GENEMANIA was used to build protein-protein interaction (PPI) networks. Enrichment analyses were performed to explore the functions. Validation datasets were selected to verify the diagnostic marker reliability of PLAGL1. The immune microenvironment of diseases was analyzed by immune infiltration analyses. Results: We confirmed a hub gene called PLAGL1, which is significantly under-expressed in both OP and MM. We found hub genes were associated with glucose and energy metabolism. Subsequently, the reliability of PLAGL1 for diagnosing OP and MM was verified using ROC curves, with all areas under the curve > 0.75. Moreover, PLAGL1 regulates t lymphocytes and may participate in the occurrence of OP in MM through immune pathways. Conclusions: PLAGL1 is a hub gene for the co-occurrence of OP and MM. It can regulate T-lymphocyte involvement in disease development. PLAGL1 may be a novel diagnostic marker for the co-occurrence of OP and MM.展开更多
BACKGROUND Multiple myeloma(MM)is a common hematologic malignancy that originates from a malignant clone of plasma cells.Solitary plasmacytoma,history of diabetes,and platelet count are considered as prognostic factor...BACKGROUND Multiple myeloma(MM)is a common hematologic malignancy that originates from a malignant clone of plasma cells.Solitary plasmacytoma,history of diabetes,and platelet count are considered as prognostic factors for MM.But some patients are still associated with much worse outcomes without any prognostic predictors.This study aimed to observe the reduction rate of monoclonal protein(M protein)after the first and fourth chemotherapy cycles,which is considered as a new prognostic factor for progression-free survival(PFS)in standard-risk group of newly diagnosed MM patients.AIM To investigate the reduction rate of M protein after first and fourth cycle chemotherapy as a useful prognostic factor.METHODS A total of 316 patients diagnosed with MM for the first time between 2010 and 2019 at the Lishui Municipal Central Hospital were included.All patients were diagnosed according to the National Comprehensive Cancer Network(NCCN)2020.V1 diagnostic criteria.The risk assessment was performed by the Mayo Stratification for Macroglobulinemia and Risk-Adapted Therapy guidelines.After diagnosis,164 patients were evaluated and underwent treatment with four to eight courses of continuous induction chemotherapy.The patients with no response after induction treatment were administered additional therapy following the NCCN 2020.V1 criteria.The following baseline data from the patients were collected:Gender,age at diagnosis,Durie-Salmon stage,glutamicpyruvic transaminase,glutamic-oxaloacetic transaminase,catabolite activator protein,albumin/globulin ratio,lactate dehydrogenase,translocation(t)(6;14),t(11;14),maintenance regimen,total cholesterol(TC),triglyceride,and phosphorous.All baseline data and the reduction rate of M protein after each chemotherapy cycle from the first to fourth were assessed by univariate analysis.The factors influencing the overall survival and PFS were then assessed by multivariate analysis.We found the first cycle(C1)reduction rate and the fourth cycle(C4)reduction rate as predictors of PFS.Then,PFS was compared between patients with a C1 reduction rate of M protein of≥25%vs<25%and≥50%vs<50%,and between patients with a C4 reduction rate of≥25%vs<25%,≥50%vs<50%,and≥75%vs<75%.RESULTS Multivariate analysis revealed age[hazard ratio(HR):1.059,95%confidence interval(95%CI):1.033-1.085,P≤0.001],International Staging System stage(HR:2.136,95%CI:1.500-3.041,P≤0.001),autotransplantion(HR:0.201,95%CI:0.069-0.583,P=0.019),TC(HR:0.689,95%CI:0.533-0.891,P=0.019),C1 reduction rate(HR:0474,95%CI:0.293-0.767,P=0.019),and C4 reduction rate(HR:0.254,95%CI:0.139-0.463,P=0.019)as predictors of PFS.The Kaplan-Meier survival analysis and the log-rank tests revealed that a higher reduction rate of M protein after first cycle(≥50%)and fourth cycle(≥75%)chemotherapy was associated with a longer PFS than the lower one.CONCLUSION Higher reduction rates of M protein after the first and fourth chemotherapy cycles can act as advantageous prognostic factors for PFS in standard-risk group of MM patients during initial diagnosis.展开更多
Introduction: Induction therapy followed by high-dose chemotherapy with autologous stem cell transplantation remains the gold standard for myeloma patients who can tolerate this treatment approach. In a developing cou...Introduction: Induction therapy followed by high-dose chemotherapy with autologous stem cell transplantation remains the gold standard for myeloma patients who can tolerate this treatment approach. In a developing country setting, in the absence of availability of bone marrow transplantation, the CTD protocol is an accessible treatment regimen whose efficacy and lower toxicity compared to the Melphalan Prednisone protocol has been reported. This protocol has been administered since 2018 in first line. It’s against this backdrop we perform this study to assess the efficacy of this CTD protocol in first line therapy. Methods: We conducted a descriptive and analytical study including clinical, paraclinical and evolutionary data of 50 patients with MM treated during the period range from 01 September 2018 and 01 July 2022 with the CTD protocol of cyclophosphamide (500 mg at D1, D8 and D15), dexamethasone (40 mg weekly) and thalidomide (100 mg/day) in 28-day cycles. Survival outcomes were estimated by the Kaplan-Meier method. Results: The mean age was 62.3 ± 9.1 years and the sex ratio was 0.7. An advanced prognostic score at diagnosis was found in 73.5% of patients according to the Salmon and Durie score and in 32% according to the ISS. Overall remission was noted in 64%, of which 34% were in very good partial remission and partial remission in 12% of cases. Progression was noted in 4 patients. Treatment-related side effects were mainly peripheral neuropathy and anaemia in 3 patients respectively. The median survival was 38.4 months. The progression-free survival was 60%. An advanced age (≥65 years) is correlated with negative impact on survival (p = 0.04). Conclusion: Cyclophosphamide, thalidomide and dexamethasone give good outcome with less toxicity. Thus, it remains a first-line treatment alternative for newly diagnosed and low-income patients.展开更多
Multiple myeloma (MM) is both a complex and heterogeneous disease. Cytogenetic and molecular abnormalities lead to resistance to treatment and transformation to plasma cell leukemia, which is defined by the presence i...Multiple myeloma (MM) is both a complex and heterogeneous disease. Cytogenetic and molecular abnormalities lead to resistance to treatment and transformation to plasma cell leukemia, which is defined by the presence in circulating blood of plasma cells over 2 G/L, or more than 20% of leukocytes. It is an uncommon hematological malignancy with a poor prognosis. Against this backdrop, we report an observation of multiple myeloma transformed into plasma cell leukemia diagnosed at the Hôpital Principal de Dakar (HPD) that occurred on a 64-year-old man with a history of thyroidectomy followed for multiple myeloma presenting with Salmon et Durie stage IIIA and ISS stage I. Despite a marked improvement in management strategy, myeloma remains an almost invariably incurable disease. However, the development of genetic and molecular biomarkers is necessary to improve its prognosis.展开更多
Multiple myeloma(MM)is the second most common malignancy in hematology.MM is characterized by the malignant proliferation of plasma cells in the bone marrow,accompanied by the secretion of monoclonal immunoglobulin,ma...Multiple myeloma(MM)is the second most common malignancy in hematology.MM is characterized by the malignant proliferation of plasma cells in the bone marrow,accompanied by the secretion of monoclonal immunoglobulin,mainly occurring in the elderly.The clinical manifestations of MM include renal dysfunction,bone destruction,infection,anemia,hemorrhage,hypercalcemia,and hyperviscosity syndrome.The recent discovery of biomarkers related to the diagnosis or prognosis of MM provides an important basis for the diagnosis and treatment of MM.This paper reviews the research progress of biomarkers expressed in tissues and peripheral blood at home and abroad.展开更多
BACKGROUND Smoldering multiple myeloma(SMM)is an asymptomatic plasma cell proliferative disorder that can progress to multiple myeloma(MM).Amyloidosis(light chain)(AL)is the most common form of systemic amyloidosis.Th...BACKGROUND Smoldering multiple myeloma(SMM)is an asymptomatic plasma cell proliferative disorder that can progress to multiple myeloma(MM).Amyloidosis(light chain)(AL)is the most common form of systemic amyloidosis.There are few reports of SMM coexisting with AL involving the digestive tract.CASE SUMMARY A 63-year-old woman presented with lower limb edema,abdominal distension,abdominal pain,and hematochezia.Gastroscopy showed gastric retention,gastric angler mucosal coarseness,hyperemia,and mild oozing of blood.Colonoscopy showed hyperemic and edematous mucosa of the distal ascending colon and sigmoid colon with the presence of multiple round and irregular ulcers,submucosal ecchymosis,and hematoma.Gastric and colonic tissue biopsy confirmed the diagnosis of AL by positive Congo red staining.MM was confirmed by bone marrow biopsy and immunohistochemistry.The patient had no hypercalcemia,renal dysfunction,anemia,bone lesions or biomarkers of malignancy defined as plasma cells>60%in bone marrow.Additionally,no elevated serum free light chain ratio,or presence of bone marrow lesions by magnetic resonance imaging(SLiM criteria)were detected.The patient was finally diagnosed with SMM coexisting with AL.She received chemotherapy and was discharged when the symptoms were relieved.She is doing well at nearly five years of follow up.CONCLUSION This case highlights that high index of suspicion is required to diagnose gastrointestinal AL.It should be suspected in elderly patients with endoscopic findings of granular-appearing mucosa,ecchymosis,and submucosal hematoma.Timely diagnosis and appropriate therapy can help to improve the prognosis of these patients.展开更多
BACKGROUND Immunoglobulin D(IgD)multiple myeloma(MM)is a rare subtype of MM and commonly occurs in younger subjects but at a later stage of the International Staging System(ISS)when admitted.As a special type of IgD m...BACKGROUND Immunoglobulin D(IgD)multiple myeloma(MM)is a rare subtype of MM and commonly occurs in younger subjects but at a later stage of the International Staging System(ISS)when admitted.As a special type of IgD myeloma,IgD-λ/λbiclonal MM is rarer.Its serum protein electrophoresis and serum immunofixation electrophoresis(IFE)might find no anomalies even if the bone marrow(BM)examination is performed.Thus,it is easy to miss the diagnosis.CASE SUMMARY A 62-year-old man diagnosed as IgD-λ/λmyeloma(ISS stage III)was admitted with fatigue and weight loss.The physical examination suggested an anemic face,a few moist rales at the left lung base,and mild concave edema in both lower extremities.Laboratory examinations showed the elevated creatinine levels,β2-microglobulin,lactic dehydrogenase,and erythrocyte sedimentation rate,while the decreased neutrophils,granulocytes,and hemoglobin.In the serum protein electrophoresis,there appeared two inconspicuous M-spikes.Serum IFE indicated an over-representation of lambda light chain and yielded two monoclonal bands inλregion,but only one corresponding heavy chain band in the antisera to IgD region.The BM histology and BM cytology both supported the diagnosis of IgD-λ/λmyeloma.CONCLUSION This case highlights the differential clinical manifestations and laboratory findings of IgD-λ/λmyeloma to help minimize the chance of misdiagnosis.展开更多
Medical imaging is of crucial importance for diagnosis and initial staging as well as for differentiation of multiple myeloma(MM)from other monoclonal plasma cell diseases.Conventional radiography represents the refer...Medical imaging is of crucial importance for diagnosis and initial staging as well as for differentiation of multiple myeloma(MM)from other monoclonal plasma cell diseases.Conventional radiography represents the reference standard for diagnosis of MM due to its wide availability and low costs despite its known limitations such as low sensitivity,limited specificity and its inability to detect extraosseous lesions.Besides conventional radiography,newer cross-sectional imaging modalities such as whole-body low-dose computed tomography(CT),whole-body magnetic resonance imaging(MRI)and18F-fluorodeoxyglucose(FDG)positron emission tomography(PET)/CT are available for the diagnosis of osseous and extraosseous manifestations of MM.Whole-body low-dose CT is used increasingly,replacing conventional radiography at selected centers,due to its higher sensitivity for the detection of osseous lesions and its ability to diagnose extraosseous lesions.The highest sensitivity for both detection of bone marrow disease and extraosseous lesions can be achieved with whole-body MRI and18F-FDG PET/CT.According to current evidence,MRI is the most sensitive method for initial staging while18F-FDG PET/CT allows monitoring of treatment of MM.There is an evolving role for assessment of treatment response using newer MR imagingtechniques.Future studies are needed to further define the exact role of the different imaging modalities for individual risk stratification and therapy monitoring.展开更多
This study was designed to determine the impact of chrysoeriol on proliferation and cell cycle progression in the human multiple myeloma cell lines RPMI 8226 and KM3,and its related molecular mechanisms.Chryseoriol wa...This study was designed to determine the impact of chrysoeriol on proliferation and cell cycle progression in the human multiple myeloma cell lines RPMI 8226 and KM3,and its related molecular mechanisms.Chryseoriol was identified by using the phosphorylated AKT-specific cytoblot high throughput assay.CCK-8 assay was employed to examine the growth inhibition rate and IC 50 (48 h) in peripheral blood mononuclear cells (PBMNCs),RPMI 8226 and KM3 cells treated with chrysoeriol at various concentrations.Cells were labeled with 5-6-carboxyfluorescein diacetate succinimidyl ester (CFSE),and the proliferation dynamics was detected by flow cytometry and analyzed with ModFit software.The cell cycles of RPMI 8226 and KM3 cells were measured by flow cytometry when the IC 50 concentration of chrysoeriol was adopted.The alterations in cell-cycle related proteins (Cyclin B1,Cyclin D1,p21) and proteins in PI3K-AKT-mTOR pathway were determined by Western blot analysis.The results showed the proliferation of multiple myeloma cells was significantly inhibited by chrysoeriol,resulting in cell cycle arrest in G 2 /M phase.Chrysoeriol could significantly reduce the expression of p-AKT (s473) and p-4eBP1 (t37/46) protein,meanwhile enhanced Cyclin B1 and p21 protein expression.Similar effects were not observed in PBMNCs from normal donors.It was concluded that chrysoeriol was a selective PI3K-AKT-mTOR pathway inhibitor.It restrained the proliferation of human multiple myeloma cells,but didn't affect proliferation of PBMNCs from normal donors.It might exhibit the cell cycle regulatory effect via the inhibition of PI3K-AKT-mTOR signal pathway.展开更多
In this study,we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m 2 with dexamethasone(BD) and compared it to the standard 1.3 mg/m 2 twice-weekly BD regimen in Chinese patients with newly...In this study,we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m 2 with dexamethasone(BD) and compared it to the standard 1.3 mg/m 2 twice-weekly BD regimen in Chinese patients with newly diagnosed multiple myeloma(MM).We assessed the difference in efficacy,safety profile and survival between the once-weekly and twice-weekly cohorts(13 vs.24 patients).The over response rate was similar with both arms of the study,being 77% in the once-weekly schedule and 74.9% in the twice-weekly schedule(P=0.690).The median overall survival was not reached in either schedule.Also,the median progression-free survival and duration of response of the once-weekly schedule did not significantly differ from those of the twice-weekly schedule(8 months vs.10 months,P=0.545 and 6 months vs.7 months,P=0.467 respectively).Peripheral sensory neuropathy and grade 3/4 hematologic toxic effects were more frequently reported in the twice-weekly schedule than the once-weekly schedule,but there was no statistically significant difference.This preliminary experience in Chinese patients with newly diagnosed MM indicated that once-weekly infusion of Bortezomib plus dexamethasone may improve safety without affecting outcome.展开更多
基金supported by Incubation Program for Clinical Trials(No.19HXFH030)Achievement Transformation Project(No.CGZH21001)+4 种基金1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21007)Translational Research Grant of NCRCH(No.2021WWB03),Chengdu Science and Technology Program(No.2022-YF05-01444-SN)Key Research and Development Program of Sichuan Province(No.2023YFS0031)Post-Doctor Research Project,West China Hospital,Sichuan University(No.2023HXBH111)National Key Research and Development Program of China(Nos.2022YFC2502600,2022YFC2502603).
文摘Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.
基金Research Projects-Joint Fund for Applied Basic Research of Kunming Medical University,Yunnan Provincial Department of Science and Technology(No.2018FE001(-113),No.202301AY070001-098)Open project of Yunnan Clinical Medical Center(Nos.2020LCZXKF-XY02,XY06,XY16+1 种基金2022LCZXKF-XY02)Yunnan Health Training Project of High Level Talents(No.D–2018018).
文摘Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.
基金National Key Research and Development Program of China,No.2021YFC2701704the National Clinical Medical Research Center for Geriatric Diseases,"Multicenter RCT"Research Project,No.NCRCG-PLAGH-20230010the Military Logistics Independent Research Project,No.2022HQZZ06.
文摘BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.
基金supported by grants from CAMS Innovation Fund for Medical Sciences(CIFMSGrant No.2022-I2M-1-022)。
文摘Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).
文摘BACKGROUND Extramedullary multiple myeloma(MM)(EMM)is a rare and aggressive subentity of MM that can be present at diagnosis or develop anytime during the disease course.There is a paucity of data on the clinical characteristics and overall epidemiology of EMM.Furthermore,there is a scarcity of data on how the interaction of age and gender influences the survival of EMM.AIM To evaluate the clinical characteristics of patients with EMM over the past 2 decades and to identify epidemiologic characteristics that may impact overall prognosis.METHODS A total of 858 patients diagnosed with EMM,between 2000 and 2017,were ultimately enrolled in our study by retrieving the Surveillance,Epidemiology,and End Results database.We analyzed demographics,clinical characteristics,and overall mortality(OM)as well as cancer-specific mortality(CSM)of EMM.Variables with a P value<0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors,with a hazard ratio(HR)of greater than 1 representing adverse prognostic factors.RESULTS From a sample of 858 EMM,the male gender(63.25%),age range 60-79 years(51.05%),and non-Hispanic whites(66.78%)were the most represented.Central Nervous System and the vertebral column was the most affected site(33.10%).Crude analysis revealed higher OM in the age group 80+[HR=6.951,95%confidence interval(95%CI):3.299-14.647,P=0],Non-Hispanic Black population(HR=1.339,95%CI:1.02-1.759,P=0.036),Bones not otherwise specified(NOS)(HR=1.74,95%CI:1.043-2.902,P=0.034),and widowed individuals(HR=2.107,95%CI:1.511-2.938,P=0).Skin involvement(HR=0.241,95%CI:0.06-0.974,P=0.046)and a yearly income of$75000+(HR=0.259,95%CI:0.125-0.538,P=0)had the lowest OM in the crude analysis.Crude analysis revealed higher CSM in the age group 80+,Non-Hispanic Black,Bones NOS,and widowed.Multivariate cox proportional hazard regression analyses only revealed higher OM in the age group 80+(HR=9.792,95%CI:4.403-21.774,P=0)and widowed individuals(HR=1.609,95%CI:1.101-2.35,P=0.014).Multivariate cox proportional hazard regression analyses of CSM also revealed higher mortality of the same groups.Eyes,mouth,and ENT involvement had the lowest CSM in the multivariate analysis.There was no interaction between age and gender in the adjusted analysis for OM and CSM.CONCLUSION EMM is a rare entity.To our knowledge,there is a scarcity of data on the clinical characteristics and prognosis factors of patients with extramedullary multiple myeloma.In this retrospective cohort,using a United States-based population,we found that age,marital status,and tumor site were independent prognostic factors.Furthermore,we found that age and gender did not interact to influence the mortality of patients with EMM.
基金supported by the International Cooperation Projects of National Natural Science Foundation of China(Grant No.81920108006,to L.Qiu)CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2022-I2M-1-022,to L.Qiu)+1 种基金the National Natural Science Foundation of China(Grant No.81630007,to L.QiuGrant Nos.82270218,81670202,to G.An)。
文摘Introduction Multiple myeloma(MM),characterized by the proliferation of monoclonal plasma cells in the bone marrow,has the second highest incidence among hematologic malignancies1.Because of its incurable nature,treatments for MM are aimed primarily at obtaining minimal residual disease(MRD)negativity and achieving persistent control,both of which are believed to be important strategies to prolong survival and improve prognosis in patients with MM.
基金supported by grants from the National Natural Science Foundation of China(No.82070208)the Military Clinical Medical Innovation Project of Xinqiao Hospital(No.2021JSLC0003)+2 种基金the National Natural Science Foundation of Chongqing(No.cstc2020jcyjmsxmX0433)the Translational Research Grant of NCRCH(Nos.2020ZKZC02,2021WWB05)the Chongqing Science and Health Joint Medical Research Project(Nos.2021MSXM226,2023QNXM047).
文摘Objective:Metabolic disorders are regarded as hallmarks of multiple myeloma(MM)and are responsible for rapid cancer cell proliferation and tumor growth.However,the exact biological roles of metabolites in MM cells have not been fully explored.This study aimed to explore the feasibility and clinical significance of lactate for MM and investigate the molecular mechanism of lactic acid(Lac)in the proliferation of myeloma cells and cell sensitivity to bortezomib(BTZ).Methods:Metabolomic analysis of the serum was carried out to obtain metabolites expression and clinical characteristics in MM patients.The CCK8 assay and flow cytometry were used to detect cell proliferation,apoptosis,and cell cycle changes.Western blotting was used to detect the potential mechanism and apoptosis-and cycle-related protein changes.Results:Lactate was highly expressed in both the peripheral blood and bone marrow of MM patients.It was significantly correlated with Durie-Salmon Staging(DS Staging)and the International Staging System(ISS Staging)and the serum and urinary involved/uninvolved free light chain ratios.Patients with relatively high lactate levels had a poor treatment response.Moreover,in vitro experiments showed that Lac could promote the proliferation of tumor cells and decrease the proportion of G0/G1-phase cells,which was accompanied by an increased proportion of S-phase cells.In addition,Lac could decrease tumor sensitivity to BTZ by disrupting the expression of nuclear factor kappa B subunit 2(NFκB2)and Re1B.Conclusion:Metabolic changes are important in MM cell proliferation and treatment response;lactate could be used as a biomarker in MM and as a therapeutic target to overcome cell resistance to BTZ.
文摘Novel drug availability has increased the depth of response and revolutionised the outcomes of multiple myeloma patients.Minimal residual disease evaluation is a surrogate for progression-free survival and overall survival and has become widely used not-only in clinical trials but also in daily patient management.Bone marrow aspiration is the gold standard for response evaluation,but due to the patchy nature of myeloma,false negatives are possible.Liquid biopsy and blood-based minimal residual disease evaluation consider circulating plasma cells,mass spectrometry or circulating tumour DNA.This approach is less invasive,can provide a more comprehensive picture of the disease and could become the future of response evaluation in multiple myeloma patients.
基金Supported by The“Instituto de Salud Carlos III,No.PI22/00264A Predoctoral Program in Biomedicine from The University of Cantabria and The Instituto de Investigación Valdecilla-IDIVAL(Alberto González-González and Daniel García-Sánchez),No.PREVAL19/02,and No.PREVAL20/01“Investigo Program”,part of the“Plan Nacional de Recuperación,Transformación y Resiliencia”from The Spanish Government(Mónica del Dujo-Gutiérrez).
文摘Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,and specifically BM mesenchymal stem cells(BM-MSCs),has a key role in the pathophysiology of this disease.Multiple data support the idea that BM-MSCs not only enhance the proliferation and survival of MM cells but are also involved in the resistance of MM cells to certain drugs,aiding the progression of this hematological tumor.The relation of MM cells with the resident BM-MSCs is a two-way interaction.MM modulate the behavior of BM-MSCs altering their expression profile,proliferation rate,osteogenic potential,and expression of senescence markers.In turn,modified BM-MSCs can produce a set of cytokines that would modulate the BM microenvironment to favor disease progression.The interaction between MM cells and BM-MSCs can be mediated by the secretion of a variety of soluble factors and extracellular vesicles carrying microRNAs,long non-coding RNAs or other molecules.However,the communication between these two types of cells could also involve a direct physical interaction through adhesion molecules or tunneling nanotubes.Thus,understanding the way this communication works and developing strategies to interfere in the process,would preclude the expansion of the MM cells and might offer alternative treatments for this incurable disease.
文摘BACKGROUND The treatment of multiple myeloma has significantly progressed over the past half-century.The purpose of this study was to perform a systematic review and meta-analysis in order to explore the efficacy and safety of daratumumab in treating multiple myeloma.AIM To explore the efficacy and safety of daratumumab in treating multiple myeloma.METHODS A systematic literature search was performed using Chinese and English databases,including the China National Knowledge Infrastructure,Wanfang,China Biology Medicine,VIP,the Cochrane Library,Embase,and PubMed.The search encompassed studies in treating multiple myeloma with daratumumab,spanning from the inception of the database to June 2023.Revman 5.1 software was used for analysis.RESULTS Our analysis included eight English articles and one Chinese article of high quality.The meta-analysis results indicated that compared to other therapies,daratumumab could improve the overall response rate(ORR)[odds ratio(OR)=2.67,95%confidence interval(CI)=2.01,3.53,Z=6.85,P<0.00001],complete remission(CR)(OR=2.87,95%CI=2.16,3.83,Z=7.23,P<0.00001)and progression-free survival(PFS)time(hazard ratio=0.48,95%CI=0.38,0.60,Z=6.54,P<0.00001)in patients with multiple myeloma.These differences were statistically significant.Additionally,these results suggested that daratumumab increases the risk of neutropenia and thrombocytopenia with minimal effect on the incidences of anemia and upper respiratory tract infections.CONCLUSION Daratumumab can improve ORR,CR rate,and PFS in patients with multiple myeloma.It also increases the risk of neutropenia and thrombocytopenia,necessitating careful monitoring during its clinical application.
文摘Background: Osteoporosis (OP) is a common clinical manifestation of multiple myeloma (MM). The aim of this study was to investigate the possible molecular pathways and shared genes in the co-occurrence of OP and MM. Methods: The Gene Expression Omnibus database was used to retrieve gene expression information. Use WGCNA and differential analysis to screen out Hub genes. The GENEMANIA was used to build protein-protein interaction (PPI) networks. Enrichment analyses were performed to explore the functions. Validation datasets were selected to verify the diagnostic marker reliability of PLAGL1. The immune microenvironment of diseases was analyzed by immune infiltration analyses. Results: We confirmed a hub gene called PLAGL1, which is significantly under-expressed in both OP and MM. We found hub genes were associated with glucose and energy metabolism. Subsequently, the reliability of PLAGL1 for diagnosing OP and MM was verified using ROC curves, with all areas under the curve > 0.75. Moreover, PLAGL1 regulates t lymphocytes and may participate in the occurrence of OP in MM through immune pathways. Conclusions: PLAGL1 is a hub gene for the co-occurrence of OP and MM. It can regulate T-lymphocyte involvement in disease development. PLAGL1 may be a novel diagnostic marker for the co-occurrence of OP and MM.
文摘BACKGROUND Multiple myeloma(MM)is a common hematologic malignancy that originates from a malignant clone of plasma cells.Solitary plasmacytoma,history of diabetes,and platelet count are considered as prognostic factors for MM.But some patients are still associated with much worse outcomes without any prognostic predictors.This study aimed to observe the reduction rate of monoclonal protein(M protein)after the first and fourth chemotherapy cycles,which is considered as a new prognostic factor for progression-free survival(PFS)in standard-risk group of newly diagnosed MM patients.AIM To investigate the reduction rate of M protein after first and fourth cycle chemotherapy as a useful prognostic factor.METHODS A total of 316 patients diagnosed with MM for the first time between 2010 and 2019 at the Lishui Municipal Central Hospital were included.All patients were diagnosed according to the National Comprehensive Cancer Network(NCCN)2020.V1 diagnostic criteria.The risk assessment was performed by the Mayo Stratification for Macroglobulinemia and Risk-Adapted Therapy guidelines.After diagnosis,164 patients were evaluated and underwent treatment with four to eight courses of continuous induction chemotherapy.The patients with no response after induction treatment were administered additional therapy following the NCCN 2020.V1 criteria.The following baseline data from the patients were collected:Gender,age at diagnosis,Durie-Salmon stage,glutamicpyruvic transaminase,glutamic-oxaloacetic transaminase,catabolite activator protein,albumin/globulin ratio,lactate dehydrogenase,translocation(t)(6;14),t(11;14),maintenance regimen,total cholesterol(TC),triglyceride,and phosphorous.All baseline data and the reduction rate of M protein after each chemotherapy cycle from the first to fourth were assessed by univariate analysis.The factors influencing the overall survival and PFS were then assessed by multivariate analysis.We found the first cycle(C1)reduction rate and the fourth cycle(C4)reduction rate as predictors of PFS.Then,PFS was compared between patients with a C1 reduction rate of M protein of≥25%vs<25%and≥50%vs<50%,and between patients with a C4 reduction rate of≥25%vs<25%,≥50%vs<50%,and≥75%vs<75%.RESULTS Multivariate analysis revealed age[hazard ratio(HR):1.059,95%confidence interval(95%CI):1.033-1.085,P≤0.001],International Staging System stage(HR:2.136,95%CI:1.500-3.041,P≤0.001),autotransplantion(HR:0.201,95%CI:0.069-0.583,P=0.019),TC(HR:0.689,95%CI:0.533-0.891,P=0.019),C1 reduction rate(HR:0474,95%CI:0.293-0.767,P=0.019),and C4 reduction rate(HR:0.254,95%CI:0.139-0.463,P=0.019)as predictors of PFS.The Kaplan-Meier survival analysis and the log-rank tests revealed that a higher reduction rate of M protein after first cycle(≥50%)and fourth cycle(≥75%)chemotherapy was associated with a longer PFS than the lower one.CONCLUSION Higher reduction rates of M protein after the first and fourth chemotherapy cycles can act as advantageous prognostic factors for PFS in standard-risk group of MM patients during initial diagnosis.
文摘Introduction: Induction therapy followed by high-dose chemotherapy with autologous stem cell transplantation remains the gold standard for myeloma patients who can tolerate this treatment approach. In a developing country setting, in the absence of availability of bone marrow transplantation, the CTD protocol is an accessible treatment regimen whose efficacy and lower toxicity compared to the Melphalan Prednisone protocol has been reported. This protocol has been administered since 2018 in first line. It’s against this backdrop we perform this study to assess the efficacy of this CTD protocol in first line therapy. Methods: We conducted a descriptive and analytical study including clinical, paraclinical and evolutionary data of 50 patients with MM treated during the period range from 01 September 2018 and 01 July 2022 with the CTD protocol of cyclophosphamide (500 mg at D1, D8 and D15), dexamethasone (40 mg weekly) and thalidomide (100 mg/day) in 28-day cycles. Survival outcomes were estimated by the Kaplan-Meier method. Results: The mean age was 62.3 ± 9.1 years and the sex ratio was 0.7. An advanced prognostic score at diagnosis was found in 73.5% of patients according to the Salmon and Durie score and in 32% according to the ISS. Overall remission was noted in 64%, of which 34% were in very good partial remission and partial remission in 12% of cases. Progression was noted in 4 patients. Treatment-related side effects were mainly peripheral neuropathy and anaemia in 3 patients respectively. The median survival was 38.4 months. The progression-free survival was 60%. An advanced age (≥65 years) is correlated with negative impact on survival (p = 0.04). Conclusion: Cyclophosphamide, thalidomide and dexamethasone give good outcome with less toxicity. Thus, it remains a first-line treatment alternative for newly diagnosed and low-income patients.
文摘Multiple myeloma (MM) is both a complex and heterogeneous disease. Cytogenetic and molecular abnormalities lead to resistance to treatment and transformation to plasma cell leukemia, which is defined by the presence in circulating blood of plasma cells over 2 G/L, or more than 20% of leukocytes. It is an uncommon hematological malignancy with a poor prognosis. Against this backdrop, we report an observation of multiple myeloma transformed into plasma cell leukemia diagnosed at the Hôpital Principal de Dakar (HPD) that occurred on a 64-year-old man with a history of thyroidectomy followed for multiple myeloma presenting with Salmon et Durie stage IIIA and ISS stage I. Despite a marked improvement in management strategy, myeloma remains an almost invariably incurable disease. However, the development of genetic and molecular biomarkers is necessary to improve its prognosis.
文摘Multiple myeloma(MM)is the second most common malignancy in hematology.MM is characterized by the malignant proliferation of plasma cells in the bone marrow,accompanied by the secretion of monoclonal immunoglobulin,mainly occurring in the elderly.The clinical manifestations of MM include renal dysfunction,bone destruction,infection,anemia,hemorrhage,hypercalcemia,and hyperviscosity syndrome.The recent discovery of biomarkers related to the diagnosis or prognosis of MM provides an important basis for the diagnosis and treatment of MM.This paper reviews the research progress of biomarkers expressed in tissues and peripheral blood at home and abroad.
文摘BACKGROUND Smoldering multiple myeloma(SMM)is an asymptomatic plasma cell proliferative disorder that can progress to multiple myeloma(MM).Amyloidosis(light chain)(AL)is the most common form of systemic amyloidosis.There are few reports of SMM coexisting with AL involving the digestive tract.CASE SUMMARY A 63-year-old woman presented with lower limb edema,abdominal distension,abdominal pain,and hematochezia.Gastroscopy showed gastric retention,gastric angler mucosal coarseness,hyperemia,and mild oozing of blood.Colonoscopy showed hyperemic and edematous mucosa of the distal ascending colon and sigmoid colon with the presence of multiple round and irregular ulcers,submucosal ecchymosis,and hematoma.Gastric and colonic tissue biopsy confirmed the diagnosis of AL by positive Congo red staining.MM was confirmed by bone marrow biopsy and immunohistochemistry.The patient had no hypercalcemia,renal dysfunction,anemia,bone lesions or biomarkers of malignancy defined as plasma cells>60%in bone marrow.Additionally,no elevated serum free light chain ratio,or presence of bone marrow lesions by magnetic resonance imaging(SLiM criteria)were detected.The patient was finally diagnosed with SMM coexisting with AL.She received chemotherapy and was discharged when the symptoms were relieved.She is doing well at nearly five years of follow up.CONCLUSION This case highlights that high index of suspicion is required to diagnose gastrointestinal AL.It should be suspected in elderly patients with endoscopic findings of granular-appearing mucosa,ecchymosis,and submucosal hematoma.Timely diagnosis and appropriate therapy can help to improve the prognosis of these patients.
基金National Natural Science Foundation of China,No.81500430 and No.U1304802Science and Technology Planning Project of Henan Province,No.192102310045,No.182102310544,No.182102310566,and No.182102310573Henan Medical Science and Technology Tackling Project,No.2018020320.
文摘BACKGROUND Immunoglobulin D(IgD)multiple myeloma(MM)is a rare subtype of MM and commonly occurs in younger subjects but at a later stage of the International Staging System(ISS)when admitted.As a special type of IgD myeloma,IgD-λ/λbiclonal MM is rarer.Its serum protein electrophoresis and serum immunofixation electrophoresis(IFE)might find no anomalies even if the bone marrow(BM)examination is performed.Thus,it is easy to miss the diagnosis.CASE SUMMARY A 62-year-old man diagnosed as IgD-λ/λmyeloma(ISS stage III)was admitted with fatigue and weight loss.The physical examination suggested an anemic face,a few moist rales at the left lung base,and mild concave edema in both lower extremities.Laboratory examinations showed the elevated creatinine levels,β2-microglobulin,lactic dehydrogenase,and erythrocyte sedimentation rate,while the decreased neutrophils,granulocytes,and hemoglobin.In the serum protein electrophoresis,there appeared two inconspicuous M-spikes.Serum IFE indicated an over-representation of lambda light chain and yielded two monoclonal bands inλregion,but only one corresponding heavy chain band in the antisera to IgD region.The BM histology and BM cytology both supported the diagnosis of IgD-λ/λmyeloma.CONCLUSION This case highlights the differential clinical manifestations and laboratory findings of IgD-λ/λmyeloma to help minimize the chance of misdiagnosis.
文摘Medical imaging is of crucial importance for diagnosis and initial staging as well as for differentiation of multiple myeloma(MM)from other monoclonal plasma cell diseases.Conventional radiography represents the reference standard for diagnosis of MM due to its wide availability and low costs despite its known limitations such as low sensitivity,limited specificity and its inability to detect extraosseous lesions.Besides conventional radiography,newer cross-sectional imaging modalities such as whole-body low-dose computed tomography(CT),whole-body magnetic resonance imaging(MRI)and18F-fluorodeoxyglucose(FDG)positron emission tomography(PET)/CT are available for the diagnosis of osseous and extraosseous manifestations of MM.Whole-body low-dose CT is used increasingly,replacing conventional radiography at selected centers,due to its higher sensitivity for the detection of osseous lesions and its ability to diagnose extraosseous lesions.The highest sensitivity for both detection of bone marrow disease and extraosseous lesions can be achieved with whole-body MRI and18F-FDG PET/CT.According to current evidence,MRI is the most sensitive method for initial staging while18F-FDG PET/CT allows monitoring of treatment of MM.There is an evolving role for assessment of treatment response using newer MR imagingtechniques.Future studies are needed to further define the exact role of the different imaging modalities for individual risk stratification and therapy monitoring.
基金supported by grants from the National Natural Sciences Foundation of China(No.30770914No.30901587)China State Key Basic Research Program(No.2002CB513100)
文摘This study was designed to determine the impact of chrysoeriol on proliferation and cell cycle progression in the human multiple myeloma cell lines RPMI 8226 and KM3,and its related molecular mechanisms.Chryseoriol was identified by using the phosphorylated AKT-specific cytoblot high throughput assay.CCK-8 assay was employed to examine the growth inhibition rate and IC 50 (48 h) in peripheral blood mononuclear cells (PBMNCs),RPMI 8226 and KM3 cells treated with chrysoeriol at various concentrations.Cells were labeled with 5-6-carboxyfluorescein diacetate succinimidyl ester (CFSE),and the proliferation dynamics was detected by flow cytometry and analyzed with ModFit software.The cell cycles of RPMI 8226 and KM3 cells were measured by flow cytometry when the IC 50 concentration of chrysoeriol was adopted.The alterations in cell-cycle related proteins (Cyclin B1,Cyclin D1,p21) and proteins in PI3K-AKT-mTOR pathway were determined by Western blot analysis.The results showed the proliferation of multiple myeloma cells was significantly inhibited by chrysoeriol,resulting in cell cycle arrest in G 2 /M phase.Chrysoeriol could significantly reduce the expression of p-AKT (s473) and p-4eBP1 (t37/46) protein,meanwhile enhanced Cyclin B1 and p21 protein expression.Similar effects were not observed in PBMNCs from normal donors.It was concluded that chrysoeriol was a selective PI3K-AKT-mTOR pathway inhibitor.It restrained the proliferation of human multiple myeloma cells,but didn't affect proliferation of PBMNCs from normal donors.It might exhibit the cell cycle regulatory effect via the inhibition of PI3K-AKT-mTOR signal pathway.
文摘In this study,we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m 2 with dexamethasone(BD) and compared it to the standard 1.3 mg/m 2 twice-weekly BD regimen in Chinese patients with newly diagnosed multiple myeloma(MM).We assessed the difference in efficacy,safety profile and survival between the once-weekly and twice-weekly cohorts(13 vs.24 patients).The over response rate was similar with both arms of the study,being 77% in the once-weekly schedule and 74.9% in the twice-weekly schedule(P=0.690).The median overall survival was not reached in either schedule.Also,the median progression-free survival and duration of response of the once-weekly schedule did not significantly differ from those of the twice-weekly schedule(8 months vs.10 months,P=0.545 and 6 months vs.7 months,P=0.467 respectively).Peripheral sensory neuropathy and grade 3/4 hematologic toxic effects were more frequently reported in the twice-weekly schedule than the once-weekly schedule,but there was no statistically significant difference.This preliminary experience in Chinese patients with newly diagnosed MM indicated that once-weekly infusion of Bortezomib plus dexamethasone may improve safety without affecting outcome.
