Acute lymphoblastic leukemia (ALL) is characterized by immature and poorly differentiated B lymphocytes in large numbers in the blood. B cells are distinct from the cell types involved in their development (common lym...Acute lymphoblastic leukemia (ALL) is characterized by immature and poorly differentiated B lymphocytes in large numbers in the blood. B cells are distinct from the cell types involved in their development (common lymphoid progenitor cells, pro-B cells, pre-B cells, and mature cells). The process of B cell maturation depends on precise communication within the cell: signals activate specific genes that are essential for proper development. Errors in this intricate signaling network can lead to issues with B cell function and contribute to disease. B-lineage acute lymphoid leukemias, malignancies of precursor-stage B lymphoid cells inhibit lymphoid differentiation, leading to abnormal cell proliferation and survival. The process of developing leukemia (leukemogenesis) can be triggered by an overproduction of both hematopoietic stem cells (the cells that form all blood cells) and the immature versions of white blood cells called lymphoblasts. Acute lymphoblastic leukemia (ALL) with the presence of the Philadelphia chromosome (ALL Ph) is classified as a high-risk manifestation of the disease, this chromosome is the product of the reciprocal translocation, whose product is a BCR-ABL fusion protein. It is a highly active tyrosine kinase that can transform hematopoietic cells into cytokine-independent. Hyperphosphorylation cascades inhibit the differentiating function of IKZF1 as a tumor suppressor gene which leads to an abnormal proliferation of B cells due to the presence of the Philadelphia chromosome;it inhibits the differentiating process, leukemogenesis involving immature B cells in the bloodstream can result from the uncontrolled growth and division of hematopoietic stem cells and immature lymphoblasts (the precursors to B cells).展开更多
Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with aberrant T-cell developmental arrest. Individuals with relapsed T-ALL have limited therapeutic alternatives and po...Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with aberrant T-cell developmental arrest. Individuals with relapsed T-ALL have limited therapeutic alternatives and poor prognosis. The mitochondrial function is critical for the T-cell viability. The voltage-dependent anion channel 2 (VDAC2) in the mitochondrial outer membrane, interacts with pro-apoptotic BCL-2 proteins and mediates the apoptosis of several cancer cell lines. Objective: The aim of the current study is to explore the role of VDAC2 in T-ALL cell survival and proliferation. Methods: Publicly available datasets of RNA-seq results were analyzed for expression of VDAC isoforms and T-ALL cell lines were treated with a VDAC2 small molecular inhibitor erastin. A VDAC2 RNA interference (siRNA) was delivered to T-ALL cell lines using a retroviral vector. Functional assays were performed to investigate the VDAC2 siRNA impacts on cell proliferation, apoptosis and survival of T-ALL cells. Results: Our analysis found a high expression of VDAC2 mRNA in various T-ALL cell lines. Public datasets of T-ALL RNA-seq also showed that VDAC2 is highly expressed in T-ALL (116.2 ± 36.7), compared to control groups. Only two T-ALL cell lines showed sensitivity to erastin (20 μM) after 48 hours of incubation, including Jurkat (IC<sub>50</sub> = 3.943 μM) and Molt4 (IC<sub>50</sub> = 3.286 μM), while another two T-ALL cells (CUTLL1 and RPMI 8402) had unstable IC<sub>50</sub>. However, five T-ALL cell lines (LOUCY, CCRF-CEM, P12-ICHI, HPB-ALL, and PEER cells) showed resistance to erastin. On the contrary, all T-ALL cell lines genetically inhibited with VDAC2 siRNA led to more than 80% decrease in VDAC2 mRNA levels, and a Conclusion: VDAC2 is highly expressed in T-ALL cells. The inhibition of VDAC2 significantly decreased cell viability, increased apoptosis, reduced cell proliferation and caused cell cycle sub-G1 arrest of T-ALL cells.展开更多
Objective:To compare the effect of L-asparaginase and pegaspargase in the treatment of adult acute lymphoblastic leukemia.Methods:In this study,96 patients who received treatment at the Shaanxi Provincial People’s Ho...Objective:To compare the effect of L-asparaginase and pegaspargase in the treatment of adult acute lymphoblastic leukemia.Methods:In this study,96 patients who received treatment at the Shaanxi Provincial People’s Hospital from April 2019 to April 2021 were selected.The control group received L-asparaginase treatment,and the observation group received pegaspargase treatment.The curative effect and adverse reaction rate were compared between the two groups.Results:Comparing the experimental statistical results of the observation and the control groups,it can be concluded that the effect of the former group is better than that of the latter group in terms of clinical curative effect and statistics of adverse reactions.Conclusion:In the treatment of adult acute lymphoblastic leukemia,the application of pegaspargase therapy has a significantly better clinical effect and is worthy of further promotion.展开更多
Macrophage activation syndrome (MAS) is linked to inappropriate stimulation of macrophage cells in the bone marrow and lymphoid system, resulting in abnormal phagocytosis of figurative blood elements and the release o...Macrophage activation syndrome (MAS) is linked to inappropriate stimulation of macrophage cells in the bone marrow and lymphoid system, resulting in abnormal phagocytosis of figurative blood elements and the release of pro-inflammatory cytokines. It is a rare and serious hyper-inflammatory condition of diagnostic and therapeutic emergency. MAS is characterized by non-specific clinical and laboratory signs associated with images of hemophagocytosis. MAS is either “primary” (familial or pediatric forms), or “secondary/reactive” to infection, neoplasia, or autoimmune disease. Hemopathies dominate MAS secondary to neoplasia. B-type acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the proliferation and accumulation of B lymphoid progenitors, blocked at an early stage of differentiation, leading to suppression of polyclonal hematopoiesis and subsequent development of signs associated with bone marrow failure. In this context, we report the observation of a macrophage activation syndrome (MAS) associated with ALL, diagnosed at Hôpital Principal de Dakar/Senegal, in a 69-year-old patient with a well-controlled type 2 diabetes under oral antidiabetic therapy (OAD) and good general condition.展开更多
Relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT) remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic ...Relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT) remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine(DAC) for treating patients with acute lymphoblastic leukemia(ALL) who relapsed after allogeneic hematopoietic stem cell transplantation(allo-HSCT). We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission(CR), 1 achieved a partial remission(PR), and 1 had no response(NR) after treatment at the latest follow-up(LFU), the median survival was 11.2 months(range, 3.8–34, 7 months). The 1-and 2-year overall survival(OS) rates were 50%(6/12) and 25%(3/12), respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL(57.1% vs. 20%). No aggravated flares of graft-versus-host disease(GVHD) were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.展开更多
We performed a retrospective analysis to investigate dynamic peri-hematopoieticstem cell transplantation(HSCT)minimal/measurable residual disease(MRD)on outcomes inpatients with T-cell acute lymphoblastic leukemia(T-A...We performed a retrospective analysis to investigate dynamic peri-hematopoieticstem cell transplantation(HSCT)minimal/measurable residual disease(MRD)on outcomes inpatients with T-cell acute lymphoblastic leukemia(T-ALL).A total of 271 patients were enrolledand classified into three groups:unchanged ncgative MRD pre-and post-HSCT group(group A),post-MRD non-increase group(group B),and post-MRD increase group(group C).The patientsin group B and group C experienced a higher cumulative incidence of relapse(CIR)(42%vs.71%vs.16%,P<0.001)and lower leukemia-free survival(LFS)(46%vs.21%vs.70%,P<0.001)andoverall survival(OS)(50%vs.28%vs.72%,P<0.001)than in group A,but there was no significantdifference in non-relapse mortality(NRM)among three groups(14%vs.12%vs.8%,P=0.752).Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR(HR=2.392,95%CI,1.816-3.151,P<0.001),LFS(HR=1.964,95%CI,1.546-2.496,P<0.001)and os(HR=1.731,95%CI,1.348-2.222,P<0.001).We also established a risk scoring system based ondynamic peri-HSCT MRD combined with remission status pre-HSCT and onsct of chronic graft-versus-host disease(GVHD).This risk scoring system could better distinguish ClR(c=0.730)thanthat for pre-HSCT MRD(c=0.562),post-HSCT MRD(c=0.616)and pre-and post-MRD dynamics(c=0.648).Our results confirm the outcome predictive value of dynamic peri-HSCT MRD eitheralone or in combination with other variables for patients with T-ALL.展开更多
Objective:To explore the mechanism of drug resistance in acute lymphoblastic leukemia and the anti-tumor effect of combination therapy of dehydroabietic acid and vincristine against acute lymphoblastic leukemia cells....Objective:To explore the mechanism of drug resistance in acute lymphoblastic leukemia and the anti-tumor effect of combination therapy of dehydroabietic acid and vincristine against acute lymphoblastic leukemia cells.Methods:Acute lymphoblastic leukemia cells REH and CCRFCEM were employed to detect the anti-tumor effect of vincristine and doxorubicin on proliferation and apoptosis using EdU assay,human active caspase-3 Quantikine ELISA kit,and flow cytometry.Vincristine-resistant REH cells(REH-R),survivin knockdown and overexpressing REH cells were established to verify the role of survivin in drug resistance.Additionally,in vitro and in vivo assays were performed to determine the effect of dehydroabietic acid on the cytotoxicity of vincristine.Results:Vincristine and doxorubicin markedly suppressed proliferation and induced apoptosis of REH and CCRF-CEM cells.Survivin expression was upregulated in REH-R cells compared with REH cells.Knockdown of survivin expression obviously restored the sensitivity of REH-R cells to vincristine.Akt phosphorylation was also increased in REH-R cells compared to REH cells.In addition,LY294002,a PI3k/Akt pathway blocker,inhibited survivin expression and enhanced cytotoxicity of vincristine to REH-R cells.Dehydroabietic acid effectively reduced survivin expression in REH-R cells,thereby enhancing the therapeutic effect of vincristine on drug-resistant cells.Survivin overexpression markedly reduced the effect of dehydroabietic acid on enhancing the anti-proliferation and inducing apoptosis effect of vincristine.Moreover,the combination of dehydroabietic acid with vincristine significantly extended the survival rate in a mouse xenograft model of acute lymphoblastic leukemia,compared with vincristine treatment alone.Conclusions:Dehydroabietic acid may be used as a potential candidate for the treatment of acute lymphoblastic leukemia in combination with vincristine.展开更多
Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to eva...Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.展开更多
Objective:Cytogenetic abnormalities have been proven to be the most valuable parameter for risk stratification of childhood acute lymphoblastic leukemia(ALL).However,studies on the prevalence of cytogenetic abnormalit...Objective:Cytogenetic abnormalities have been proven to be the most valuable parameter for risk stratification of childhood acute lymphoblastic leukemia(ALL).However,studies on the prevalence of cytogenetic abnormalities and their correlation to clinical features in Chinese pediatric patients are limited,especially large-scale studies.Methods:We collected the cytogenetics and clinical data of 1541 children newly diagnosed with ALL between 2001 and 2014 in four Chinese hospitals,and retrospectively analyzed their clinical features,prognosis and risk factors associated with pediatric ALL.展开更多
Acute lymphoblastic leukemia(ALL)is a common pediatric cancer.The second malignant neoplasms(SMNs)in long-term survivors of pediatric ALL are relatively rare.Herein we report a 10-year-old girl who was diagnosed as pr...Acute lymphoblastic leukemia(ALL)is a common pediatric cancer.The second malignant neoplasms(SMNs)in long-term survivors of pediatric ALL are relatively rare.Herein we report a 10-year-old girl who was diagnosed as primitive neuroectodermal tumor(PNET)5 years after the initial diagnosis of ALL with radiotherapy・free treatment.PNET is an exceedingly rare neoplasm in SMNs of survivors of childhood ALL.It is predisposed to be misdiagnosed and the pathogenesis is unclear.The outcome is poor.Long-term follow-up is necessary for the survival children of ALL.展开更多
BACKGROUND BCR-ABL1 fusion gene is associated with a poor prognosis and a high incidence in central nervous system(CNS)leukemia.CNS invasion which detected at the initial diagnosis is commonly with bone marrow infiltr...BACKGROUND BCR-ABL1 fusion gene is associated with a poor prognosis and a high incidence in central nervous system(CNS)leukemia.CNS invasion which detected at the initial diagnosis is commonly with bone marrow infiltration.It is uncommon for the leukemia cells to be located primarily in the CNS without bone marrow involvement.CASE SUMMARY We here report the rare initial presentation of CNS-restricted BCR-ABL-positive acute lymphoblastic leukemia in a 30-year-old female patient who clinically manifested with leukemic meningitis,with no involvement in peripheral blood or bone marrow.Identification of abnormal phenotypes of blast cells,and BCR-ABL1 rearrangement in the cerebrospinal fluid alone established the diagnosis of primary CNS-isolated acute lymphocytic leukemia.The patient received a combination of intrathecal therapy and high-dose chemotherapy.But the benefits of the treatments were short-lived and she experienced recurrence.CONCLUSION Flow cytometry in combination with molecular genetic analysis improved diagnostic accuracy.New approaches that may enhance the efficacy of the existing therapies and cure CNS leukemia are required.展开更多
T-cell acute lymphoblastic leukemia(T-ALL)is a hematological tumor caused by the malignant transformation of immature T-cell progenitor cells.Emerging studies have stated that microRNAs(miRNAs)may play key roles in T-...T-cell acute lymphoblastic leukemia(T-ALL)is a hematological tumor caused by the malignant transformation of immature T-cell progenitor cells.Emerging studies have stated that microRNAs(miRNAs)may play key roles in T-ALL progression.This study aimed to investigate the roles of miR-145-3p in T-ALL cell proliferation,invasion,and apoptosis with the involvement of the nuclear factor-kappaB(NF-κB)signaling pathway.T-ALL Jurkat cells were harvested,and the expression of miR-145-3p and NF-κB-p65 was measured.Gain-and loss-of-functions of miR-145-3p and NF-κB-p65 were performed to identify their roles in the biological behaviors of Jurkat cells,including proliferation,apoptosis,and invasion.Consequently,the current study demonstrated that miR-145-3p was down-regulated while NF-κB-p65 was up-regulated in Jurkat cells.miR-145-3p directly bound to the 3’untranslated region of NF-κB-p65.Over-expression of miR-145-3p inhibited Jurkat cell proliferation,invasion,and resistance to apoptosis,while over-expression of NF-κB-p65 presented opposite trends.Co-transfection of miR-145-3p and NF-κB-p65 promoted the malignant behaviors of Jurkat cells compared to miR-145-3p transfection alone,while it reduced these behaviors of Jurkat cells compared to NF-κB-p65 transfection alone.Taken together,this study provided evidence that miR-145-3p could suppress proliferation,invasion,and resistance to the death of T-ALL cells via inactivating the NF-κB signaling pathway.展开更多
BACKGROUND Myelodysplastic syndromes(MDSs)are a group of hematological diseases caused by expansion of an abnormal clone of hematopoietic stem cells.Primary MDS is a potentially premalignant clonal disorder that may p...BACKGROUND Myelodysplastic syndromes(MDSs)are a group of hematological diseases caused by expansion of an abnormal clone of hematopoietic stem cells.Primary MDS is a potentially premalignant clonal disorder that may progress to overt acute leukemia in 25%-50%of cases.However,most of these cases evolve into acute myeloid leukemia and rarely progress to acute lymphoblastic leukemia(ALL).Thus,transformation of MDS into B-cell ALL is rare.CASE SUMMARY A 58-year-old man was admitted to the hospital for reduced blood cell counts.Based on all the test results and the World Health Organization diagnosis and classification,the patient was finally diagnosed with ring-shaped sideroblastic MDS with refractory hemocytopenia due to multilineage dysplasia.We used red blood cell transfusions and other symptomatic support treatments.After 4 years,the patient felt dizziness,fatigue,and night sweats.We improved bone marrow and peripheral blood and other related auxiliary examinations.He was eventually diagnosed with B-lineage acute lymphocytic leukemia(MDS transformation).CONCLUSION The number of peripheral blood cells,type of MDS,proportion of primitive cells in bone marrow,and number and quality of karyotypes are all closely related to the conversion of MDS to ALL.展开更多
Objective The aim of the study was to systematically evaluate the correlation between IKZF1 polymorphisms and the risk of acute lymphoblastic leukemia.Methods Computer databases including PubMed,EMBASE,and Web of Scie...Objective The aim of the study was to systematically evaluate the correlation between IKZF1 polymorphisms and the risk of acute lymphoblastic leukemia.Methods Computer databases including PubMed,EMBASE,and Web of Science were searched for case-control studies on the association between IKZF1 polymorphisms and the risk of acute lymphoblastic leukemia.The retrieval period was from the establishment of the database to November 2020.Two researchers independently screened the literature,extracted the data,evaluated the risk of bias in the included studies,and used Stata 14.0 software for meta-analysis.Results A total of 48 case-control studies were included,with 10520 and 44049 cases in the case and control groups,respectively.The meta-analysis results showed that rs4132061 and rs11978267 of IKZF1 were significantly correlated with the risk of acute lymphoblastic leukemia(ALL).Conclusion Current evidence indicates that rs4132061 and rs11978267 of IKZF1 are significantly associated with the risk of B-cell ALL.展开更多
BACKGROUNDβ-thalassemia intermedia(βTI)is one of the hemoglobinopathies.It constitutes 10%ofβ-thalassemia cases yet being associated with a better quality of life thanβ-thalassemia major(βTM).CASE SUMMARY We rece...BACKGROUNDβ-thalassemia intermedia(βTI)is one of the hemoglobinopathies.It constitutes 10%ofβ-thalassemia cases yet being associated with a better quality of life thanβ-thalassemia major(βTM).CASE SUMMARY We recently reported the first case of acute lymphoblastic leukemia(ALL)from Egypt in a child withβTM,and we herein report the first case of ALL from Egypt in a child withβTI.In this report,literature was reviewed for cases of malignancies associated withβTI and the possible factors underling the relationship between the two entities.CONCLUSION We stress that physicians should have a high index of suspicion of malignancies in thalassemia patients if they present with any suggestive symptoms or signs.展开更多
Background: The treatment used to combat acute lymphoblastic leukemia (ALL) is multidrug;therefore it is important to use active pharmacovigilance to detect, assess and analyze the likely adverse reactions which may o...Background: The treatment used to combat acute lymphoblastic leukemia (ALL) is multidrug;therefore it is important to use active pharmacovigilance to detect, assess and analyze the likely adverse reactions which may occur during the same period. Objective: To determine the frequency of adverse reactions to chemotherapeutic drugs in children with ALL. Material and Methods: Intensive pharmacovigilance was used to record the reports of adverse reactions to vincristine, L-asparaginase and the vincristine-L-asparaginase combination in children with ALL in a paediatric hospital. For each notification, the adverse reactions were analyzed in order to verify causality. Results: Forty patients were evaluated. Twenty children were female (50.0%) and 20 were male (50%). The children had a mean age, weight and height (±standard deviation: SD) of 8.1 (±3.4) years, 31.4 (±13.9) kg and 1.3 (±0.2) m, respectively. Vincristine was administered to 19 patients, vincristine plus L-asparaginase were given to 19 patients and only 2 patients used L-asparaginase. One-hundred-ninety adverse reactions were detected in the patients, with an average (±SD) of 4.8 (±2.6). Ondansetron was the drug administered for the treating of nausea and vomiting. One hundred eighty-one (95.3%) adverse reactions were identified as “definite”, 5 (2.6%) as “probable” and 4 (2.1%) as “doubtful”. Conclusions: There is a high incidence of adverse reactions by the administration of vincristine and L-asparaginase;the reactions of highest incidence were: nausea, vomiting, neutropenia, diarrhea, constipation, mucositis, headache, and abdominal pain. It is important to promote the detection, collection, reporting, assessment and treatment of ARD’s in children. It is necessary to promote the conduct further studies on pharmacovigilance with this type of treatments and to increase the duration of the studies.展开更多
Objective:Almost all leukemia patients died,fortunately now with the advancement of medicine and science and with the advent of treatment Chemotherapy,Radiotherapy,and Surgical treatment 75%of patients with leukemia w...Objective:Almost all leukemia patients died,fortunately now with the advancement of medicine and science and with the advent of treatment Chemotherapy,Radiotherapy,and Surgical treatment 75%of patients with leukemia who need treatment for up to 5 years,live longer than patients with leukemia who do not receive treatment.On the one side,in our country,Afghanistan the number of incidents has increased recently,and on the other side,we do not have data at the national level.Therefore,the child health hospital administration considered the necessary and left me to research this case in the last 6 months of 2018.Methods:This is an observational descriptive study,which observed 10,293 patients that come to the pediatric internal which 300 patients who indicate leukemia,and 200 patients with acute lymphoblastic leukemia(ALL),who were admitted to the oncology service of Andhra Gandhi Child Health Hospital in 2018 the study took place.Results:Based on the age we detect less than one year’s 10(5%)patients,1-10 years old 150(75%)patients,and more than 10 years old 40(20%)patients.Based on sex,boys were 120(60%)patients and girls 80(40%)patients.Based on clinical findings,anemia 155(77.5%)patients,fever 130(65%)patients,bleeding 90(45%)patients,spleen thickness 88(44%)patients,liver thickness 73(36.6%)patients,lymph nodes thickness 70(35.55%)patients,great pains 66(33%)patients and nervous system disorders 38(19%)patients.Conclusion:We can say with great conviction that 200 patients out of 10,293 had acute lymphoblastic leukemia.Further studies with prospective nature are required to confirm this observation.展开更多
MicroRNAs(miRNAs)are short noncoding RNAs that regulate the expression of genes by sequence-specific binding to mRNA to either promote or block its translation;they can also act as tumor suppressors(e.g.,let-7b,miR-29...MicroRNAs(miRNAs)are short noncoding RNAs that regulate the expression of genes by sequence-specific binding to mRNA to either promote or block its translation;they can also act as tumor suppressors(e.g.,let-7b,miR-29a,miR-99,mir-100,miR-155,and miR-181)and/or oncogenes(e.g.,miR-29a,miR-125b,miR-143-p3,mir-155,miR-181,miR-183,miR-196b,and miR-223)in childhood acute leukemia(AL).Differentially expressed miRNAs are important factors associated with the initiation and progression of AL.As shown in many studies,they can be used as noninvasive diagnostic and prognostic biomarkers,which are useful in monitoring early stages of AL development or during therapy(e.g.,miR-125b,miR-146b,miR-181c,and miR-4786),accurate classification of different cellular or molecular AL subgroups(e.g.,let-7b,miR-98,miR-100,miR-128b,and miR-223),and identification and development of new therapeutic agents(e.g.,mir-10,miR-125b,miR-203,miR-210,miR-335).Specific miRNA patterns have also been described for commonly used AL therapy drugs(e.g.,miR-125b and miR-223 for doxorubicin,miR-335 and miR-1208 for prednisolone,and miR-203 for imatinib),uncovering miRNAs that are associated with treatment response.In the current review,the role of miRNAs in the development,progression,and therapy monitoring of pediatric ALs will be presented and discussed.展开更多
Background: B-cell Acute lymphoblastic leukemia (B-ALL) is a neoplasm of lymphoblasts which are of B-cell lineage typically composed of small to medium sized blast cells, moderately condensed to dispersed chromatin wi...Background: B-cell Acute lymphoblastic leukemia (B-ALL) is a neoplasm of lymphoblasts which are of B-cell lineage typically composed of small to medium sized blast cells, moderately condensed to dispersed chromatin with scanty cytoplasm and inconspicuous nucleoli, involving the bone marrow and/or blood. Methods and materials: This is a prospective cross-sectional study in which 50 blood and/or bone marrow samples of newly diagnosed patients (B-ALL) were tested for immunophenotyping. All samples were prepared for surface and cytoplasmic markers including kappa and lambda human antibody for 10 minutes in dark place and then run by the Flow Cytometer. Results: 64% of the study populations were males and 36% were females. Cases were classified according to immunophenotype and the age into different subtypes and showed the following frequencies: Pro B-ALL (8%), early pre B-ALL (56%), common B-ALL (16%), Pre-B-ALL (14%) and Mature B-ALL (only 6%). Surface immunoglobulin was positive in 10% and negative in 90% of all patients, showing 100% positivity in mature B-ALL and totally negative in other subtypes. While cytoplasmic immunoglobulin was positive in 16% and negative in 84% of all patients and was positive in 100% of Pre-B-ALL and in 50% of mature B-ALL. Surface kappa was more expressed in mature B-ALL than lambda giving a ratio of 2:1, while cytoplasmic kappa:lambda was 6:1 in Pre-B-ALL. Conclusion: Kappa and lambda have important role in B-ALL classification which necessitates their presence in immunophenotyping of B-ALL.展开更多
Venous thromboembolism(VTE)is a complication in children with acute lymphoblastic leukemia(ALL).The Chinese Children’s Cancer Group-ALL-2015 protocol was carried out in China,and epidemiology,clinical characteristics...Venous thromboembolism(VTE)is a complication in children with acute lymphoblastic leukemia(ALL).The Chinese Children’s Cancer Group-ALL-2015 protocol was carried out in China,and epidemiology,clinical characteristics,and risk factors associated with VTE were analyzed.We collected data on VTE in a multiinstitutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019.First,VTE occurred in 159(2.08%)patients,including 90(56.6%)during induction therapy and 108(67.92%)in the upper extremities.T-ALL had a 1.74-fold increased risk of VTE(95%CI 1.08–2.8,P=0.022).Septicemia,as an adverse event of ALL treatment,can significantly promote the occurrence of VTE(P<0.001).Catheter-related thrombosis(CRT)accounted for 75.47%(n=120);and,symptomatic VTE,58.49%(n=93),which was more common in patients aged 12–18 years(P=0.023),non-CRT patients(P<0.001),or patients with cerebral thrombosis(P<0.001).Of the patients with VTE treated with anticoagulation therapy(n=147),4.08%(n=6)had bleeding.The VTE recurrence rate was 5.03%(n=8).Patients with VTE treated by non-ultrasoundguided venous cannulation(P=0.02),with residual thrombus(P=0.006),or with short anticoagulation period(P=0.026)had high recurrence rates.Thus,preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.展开更多
文摘Acute lymphoblastic leukemia (ALL) is characterized by immature and poorly differentiated B lymphocytes in large numbers in the blood. B cells are distinct from the cell types involved in their development (common lymphoid progenitor cells, pro-B cells, pre-B cells, and mature cells). The process of B cell maturation depends on precise communication within the cell: signals activate specific genes that are essential for proper development. Errors in this intricate signaling network can lead to issues with B cell function and contribute to disease. B-lineage acute lymphoid leukemias, malignancies of precursor-stage B lymphoid cells inhibit lymphoid differentiation, leading to abnormal cell proliferation and survival. The process of developing leukemia (leukemogenesis) can be triggered by an overproduction of both hematopoietic stem cells (the cells that form all blood cells) and the immature versions of white blood cells called lymphoblasts. Acute lymphoblastic leukemia (ALL) with the presence of the Philadelphia chromosome (ALL Ph) is classified as a high-risk manifestation of the disease, this chromosome is the product of the reciprocal translocation, whose product is a BCR-ABL fusion protein. It is a highly active tyrosine kinase that can transform hematopoietic cells into cytokine-independent. Hyperphosphorylation cascades inhibit the differentiating function of IKZF1 as a tumor suppressor gene which leads to an abnormal proliferation of B cells due to the presence of the Philadelphia chromosome;it inhibits the differentiating process, leukemogenesis involving immature B cells in the bloodstream can result from the uncontrolled growth and division of hematopoietic stem cells and immature lymphoblasts (the precursors to B cells).
文摘Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with aberrant T-cell developmental arrest. Individuals with relapsed T-ALL have limited therapeutic alternatives and poor prognosis. The mitochondrial function is critical for the T-cell viability. The voltage-dependent anion channel 2 (VDAC2) in the mitochondrial outer membrane, interacts with pro-apoptotic BCL-2 proteins and mediates the apoptosis of several cancer cell lines. Objective: The aim of the current study is to explore the role of VDAC2 in T-ALL cell survival and proliferation. Methods: Publicly available datasets of RNA-seq results were analyzed for expression of VDAC isoforms and T-ALL cell lines were treated with a VDAC2 small molecular inhibitor erastin. A VDAC2 RNA interference (siRNA) was delivered to T-ALL cell lines using a retroviral vector. Functional assays were performed to investigate the VDAC2 siRNA impacts on cell proliferation, apoptosis and survival of T-ALL cells. Results: Our analysis found a high expression of VDAC2 mRNA in various T-ALL cell lines. Public datasets of T-ALL RNA-seq also showed that VDAC2 is highly expressed in T-ALL (116.2 ± 36.7), compared to control groups. Only two T-ALL cell lines showed sensitivity to erastin (20 μM) after 48 hours of incubation, including Jurkat (IC<sub>50</sub> = 3.943 μM) and Molt4 (IC<sub>50</sub> = 3.286 μM), while another two T-ALL cells (CUTLL1 and RPMI 8402) had unstable IC<sub>50</sub>. However, five T-ALL cell lines (LOUCY, CCRF-CEM, P12-ICHI, HPB-ALL, and PEER cells) showed resistance to erastin. On the contrary, all T-ALL cell lines genetically inhibited with VDAC2 siRNA led to more than 80% decrease in VDAC2 mRNA levels, and a Conclusion: VDAC2 is highly expressed in T-ALL cells. The inhibition of VDAC2 significantly decreased cell viability, increased apoptosis, reduced cell proliferation and caused cell cycle sub-G1 arrest of T-ALL cells.
文摘Objective:To compare the effect of L-asparaginase and pegaspargase in the treatment of adult acute lymphoblastic leukemia.Methods:In this study,96 patients who received treatment at the Shaanxi Provincial People’s Hospital from April 2019 to April 2021 were selected.The control group received L-asparaginase treatment,and the observation group received pegaspargase treatment.The curative effect and adverse reaction rate were compared between the two groups.Results:Comparing the experimental statistical results of the observation and the control groups,it can be concluded that the effect of the former group is better than that of the latter group in terms of clinical curative effect and statistics of adverse reactions.Conclusion:In the treatment of adult acute lymphoblastic leukemia,the application of pegaspargase therapy has a significantly better clinical effect and is worthy of further promotion.
文摘Macrophage activation syndrome (MAS) is linked to inappropriate stimulation of macrophage cells in the bone marrow and lymphoid system, resulting in abnormal phagocytosis of figurative blood elements and the release of pro-inflammatory cytokines. It is a rare and serious hyper-inflammatory condition of diagnostic and therapeutic emergency. MAS is characterized by non-specific clinical and laboratory signs associated with images of hemophagocytosis. MAS is either “primary” (familial or pediatric forms), or “secondary/reactive” to infection, neoplasia, or autoimmune disease. Hemopathies dominate MAS secondary to neoplasia. B-type acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the proliferation and accumulation of B lymphoid progenitors, blocked at an early stage of differentiation, leading to suppression of polyclonal hematopoiesis and subsequent development of signs associated with bone marrow failure. In this context, we report the observation of a macrophage activation syndrome (MAS) associated with ALL, diagnosed at Hôpital Principal de Dakar/Senegal, in a 69-year-old patient with a well-controlled type 2 diabetes under oral antidiabetic therapy (OAD) and good general condition.
基金supported by grants from the National Natural Science Foundation of China(No.81300412 and No.81470333)
文摘Relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT) remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine(DAC) for treating patients with acute lymphoblastic leukemia(ALL) who relapsed after allogeneic hematopoietic stem cell transplantation(allo-HSCT). We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission(CR), 1 achieved a partial remission(PR), and 1 had no response(NR) after treatment at the latest follow-up(LFU), the median survival was 11.2 months(range, 3.8–34, 7 months). The 1-and 2-year overall survival(OS) rates were 50%(6/12) and 25%(3/12), respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL(57.1% vs. 20%). No aggravated flares of graft-versus-host disease(GVHD) were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.
基金the Beijing Municipal Science and Technology Commission(No.Z181100009618032)the National Natural Science Foundation of China(Nos.:81870141,82070185,81670186).
文摘We performed a retrospective analysis to investigate dynamic peri-hematopoieticstem cell transplantation(HSCT)minimal/measurable residual disease(MRD)on outcomes inpatients with T-cell acute lymphoblastic leukemia(T-ALL).A total of 271 patients were enrolledand classified into three groups:unchanged ncgative MRD pre-and post-HSCT group(group A),post-MRD non-increase group(group B),and post-MRD increase group(group C).The patientsin group B and group C experienced a higher cumulative incidence of relapse(CIR)(42%vs.71%vs.16%,P<0.001)and lower leukemia-free survival(LFS)(46%vs.21%vs.70%,P<0.001)andoverall survival(OS)(50%vs.28%vs.72%,P<0.001)than in group A,but there was no significantdifference in non-relapse mortality(NRM)among three groups(14%vs.12%vs.8%,P=0.752).Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR(HR=2.392,95%CI,1.816-3.151,P<0.001),LFS(HR=1.964,95%CI,1.546-2.496,P<0.001)and os(HR=1.731,95%CI,1.348-2.222,P<0.001).We also established a risk scoring system based ondynamic peri-HSCT MRD combined with remission status pre-HSCT and onsct of chronic graft-versus-host disease(GVHD).This risk scoring system could better distinguish ClR(c=0.730)thanthat for pre-HSCT MRD(c=0.562),post-HSCT MRD(c=0.616)and pre-and post-MRD dynamics(c=0.648).Our results confirm the outcome predictive value of dynamic peri-HSCT MRD eitheralone or in combination with other variables for patients with T-ALL.
基金supported by Suzhou Science and Technology Development Plan (SKJYD2021047)the Fundation of Suzhou Kowloon Hospital (SZJL202111 and SZJL202104)
文摘Objective:To explore the mechanism of drug resistance in acute lymphoblastic leukemia and the anti-tumor effect of combination therapy of dehydroabietic acid and vincristine against acute lymphoblastic leukemia cells.Methods:Acute lymphoblastic leukemia cells REH and CCRFCEM were employed to detect the anti-tumor effect of vincristine and doxorubicin on proliferation and apoptosis using EdU assay,human active caspase-3 Quantikine ELISA kit,and flow cytometry.Vincristine-resistant REH cells(REH-R),survivin knockdown and overexpressing REH cells were established to verify the role of survivin in drug resistance.Additionally,in vitro and in vivo assays were performed to determine the effect of dehydroabietic acid on the cytotoxicity of vincristine.Results:Vincristine and doxorubicin markedly suppressed proliferation and induced apoptosis of REH and CCRF-CEM cells.Survivin expression was upregulated in REH-R cells compared with REH cells.Knockdown of survivin expression obviously restored the sensitivity of REH-R cells to vincristine.Akt phosphorylation was also increased in REH-R cells compared to REH cells.In addition,LY294002,a PI3k/Akt pathway blocker,inhibited survivin expression and enhanced cytotoxicity of vincristine to REH-R cells.Dehydroabietic acid effectively reduced survivin expression in REH-R cells,thereby enhancing the therapeutic effect of vincristine on drug-resistant cells.Survivin overexpression markedly reduced the effect of dehydroabietic acid on enhancing the anti-proliferation and inducing apoptosis effect of vincristine.Moreover,the combination of dehydroabietic acid with vincristine significantly extended the survival rate in a mouse xenograft model of acute lymphoblastic leukemia,compared with vincristine treatment alone.Conclusions:Dehydroabietic acid may be used as a potential candidate for the treatment of acute lymphoblastic leukemia in combination with vincristine.
基金supported by the National Natural Science Foundation of China(No.81700147 and No.82070172).
文摘Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.
基金This study was supported by grants from the National Natural Science Foundation of China(No.81670136),VIVA-China Children's Cancer Foundation.
文摘Objective:Cytogenetic abnormalities have been proven to be the most valuable parameter for risk stratification of childhood acute lymphoblastic leukemia(ALL).However,studies on the prevalence of cytogenetic abnormalities and their correlation to clinical features in Chinese pediatric patients are limited,especially large-scale studies.Methods:We collected the cytogenetics and clinical data of 1541 children newly diagnosed with ALL between 2001 and 2014 in four Chinese hospitals,and retrospectively analyzed their clinical features,prognosis and risk factors associated with pediatric ALL.
文摘Acute lymphoblastic leukemia(ALL)is a common pediatric cancer.The second malignant neoplasms(SMNs)in long-term survivors of pediatric ALL are relatively rare.Herein we report a 10-year-old girl who was diagnosed as primitive neuroectodermal tumor(PNET)5 years after the initial diagnosis of ALL with radiotherapy・free treatment.PNET is an exceedingly rare neoplasm in SMNs of survivors of childhood ALL.It is predisposed to be misdiagnosed and the pathogenesis is unclear.The outcome is poor.Long-term follow-up is necessary for the survival children of ALL.
基金Supported by the Science and Technology Plan Guide Project of Fujian Province,No.2019D009.
文摘BACKGROUND BCR-ABL1 fusion gene is associated with a poor prognosis and a high incidence in central nervous system(CNS)leukemia.CNS invasion which detected at the initial diagnosis is commonly with bone marrow infiltration.It is uncommon for the leukemia cells to be located primarily in the CNS without bone marrow involvement.CASE SUMMARY We here report the rare initial presentation of CNS-restricted BCR-ABL-positive acute lymphoblastic leukemia in a 30-year-old female patient who clinically manifested with leukemic meningitis,with no involvement in peripheral blood or bone marrow.Identification of abnormal phenotypes of blast cells,and BCR-ABL1 rearrangement in the cerebrospinal fluid alone established the diagnosis of primary CNS-isolated acute lymphocytic leukemia.The patient received a combination of intrathecal therapy and high-dose chemotherapy.But the benefits of the treatments were short-lived and she experienced recurrence.CONCLUSION Flow cytometry in combination with molecular genetic analysis improved diagnostic accuracy.New approaches that may enhance the efficacy of the existing therapies and cure CNS leukemia are required.
文摘T-cell acute lymphoblastic leukemia(T-ALL)is a hematological tumor caused by the malignant transformation of immature T-cell progenitor cells.Emerging studies have stated that microRNAs(miRNAs)may play key roles in T-ALL progression.This study aimed to investigate the roles of miR-145-3p in T-ALL cell proliferation,invasion,and apoptosis with the involvement of the nuclear factor-kappaB(NF-κB)signaling pathway.T-ALL Jurkat cells were harvested,and the expression of miR-145-3p and NF-κB-p65 was measured.Gain-and loss-of-functions of miR-145-3p and NF-κB-p65 were performed to identify their roles in the biological behaviors of Jurkat cells,including proliferation,apoptosis,and invasion.Consequently,the current study demonstrated that miR-145-3p was down-regulated while NF-κB-p65 was up-regulated in Jurkat cells.miR-145-3p directly bound to the 3’untranslated region of NF-κB-p65.Over-expression of miR-145-3p inhibited Jurkat cell proliferation,invasion,and resistance to apoptosis,while over-expression of NF-κB-p65 presented opposite trends.Co-transfection of miR-145-3p and NF-κB-p65 promoted the malignant behaviors of Jurkat cells compared to miR-145-3p transfection alone,while it reduced these behaviors of Jurkat cells compared to NF-κB-p65 transfection alone.Taken together,this study provided evidence that miR-145-3p could suppress proliferation,invasion,and resistance to the death of T-ALL cells via inactivating the NF-κB signaling pathway.
基金Shandong Medicine and Health Science Technology Development Plan,No.2017WSA08039Jining Key Research and Development Program,No.2018SMNS008+1 种基金Doctoral Research Startup Foundation of Jining First People’s Hospital,No.2019003and TCM Technology Development Plan,No.20190744.
文摘BACKGROUND Myelodysplastic syndromes(MDSs)are a group of hematological diseases caused by expansion of an abnormal clone of hematopoietic stem cells.Primary MDS is a potentially premalignant clonal disorder that may progress to overt acute leukemia in 25%-50%of cases.However,most of these cases evolve into acute myeloid leukemia and rarely progress to acute lymphoblastic leukemia(ALL).Thus,transformation of MDS into B-cell ALL is rare.CASE SUMMARY A 58-year-old man was admitted to the hospital for reduced blood cell counts.Based on all the test results and the World Health Organization diagnosis and classification,the patient was finally diagnosed with ring-shaped sideroblastic MDS with refractory hemocytopenia due to multilineage dysplasia.We used red blood cell transfusions and other symptomatic support treatments.After 4 years,the patient felt dizziness,fatigue,and night sweats.We improved bone marrow and peripheral blood and other related auxiliary examinations.He was eventually diagnosed with B-lineage acute lymphocytic leukemia(MDS transformation).CONCLUSION The number of peripheral blood cells,type of MDS,proportion of primitive cells in bone marrow,and number and quality of karyotypes are all closely related to the conversion of MDS to ALL.
基金Supported by the National Key Project of Neonatal Children (No. 1311200003303)Grants from the Science and Technology Bureau of Sichuan Province (No. 2021YJ0211 to Jinlin Wu)Grants from the Health Planning Committee of Sichuan Province (No. 20PJ070 to Jinlin Wu)
文摘Objective The aim of the study was to systematically evaluate the correlation between IKZF1 polymorphisms and the risk of acute lymphoblastic leukemia.Methods Computer databases including PubMed,EMBASE,and Web of Science were searched for case-control studies on the association between IKZF1 polymorphisms and the risk of acute lymphoblastic leukemia.The retrieval period was from the establishment of the database to November 2020.Two researchers independently screened the literature,extracted the data,evaluated the risk of bias in the included studies,and used Stata 14.0 software for meta-analysis.Results A total of 48 case-control studies were included,with 10520 and 44049 cases in the case and control groups,respectively.The meta-analysis results showed that rs4132061 and rs11978267 of IKZF1 were significantly correlated with the risk of acute lymphoblastic leukemia(ALL).Conclusion Current evidence indicates that rs4132061 and rs11978267 of IKZF1 are significantly associated with the risk of B-cell ALL.
文摘BACKGROUNDβ-thalassemia intermedia(βTI)is one of the hemoglobinopathies.It constitutes 10%ofβ-thalassemia cases yet being associated with a better quality of life thanβ-thalassemia major(βTM).CASE SUMMARY We recently reported the first case of acute lymphoblastic leukemia(ALL)from Egypt in a child withβTM,and we herein report the first case of ALL from Egypt in a child withβTI.In this report,literature was reviewed for cases of malignancies associated withβTI and the possible factors underling the relationship between the two entities.CONCLUSION We stress that physicians should have a high index of suspicion of malignancies in thalassemia patients if they present with any suggestive symptoms or signs.
文摘Background: The treatment used to combat acute lymphoblastic leukemia (ALL) is multidrug;therefore it is important to use active pharmacovigilance to detect, assess and analyze the likely adverse reactions which may occur during the same period. Objective: To determine the frequency of adverse reactions to chemotherapeutic drugs in children with ALL. Material and Methods: Intensive pharmacovigilance was used to record the reports of adverse reactions to vincristine, L-asparaginase and the vincristine-L-asparaginase combination in children with ALL in a paediatric hospital. For each notification, the adverse reactions were analyzed in order to verify causality. Results: Forty patients were evaluated. Twenty children were female (50.0%) and 20 were male (50%). The children had a mean age, weight and height (±standard deviation: SD) of 8.1 (±3.4) years, 31.4 (±13.9) kg and 1.3 (±0.2) m, respectively. Vincristine was administered to 19 patients, vincristine plus L-asparaginase were given to 19 patients and only 2 patients used L-asparaginase. One-hundred-ninety adverse reactions were detected in the patients, with an average (±SD) of 4.8 (±2.6). Ondansetron was the drug administered for the treating of nausea and vomiting. One hundred eighty-one (95.3%) adverse reactions were identified as “definite”, 5 (2.6%) as “probable” and 4 (2.1%) as “doubtful”. Conclusions: There is a high incidence of adverse reactions by the administration of vincristine and L-asparaginase;the reactions of highest incidence were: nausea, vomiting, neutropenia, diarrhea, constipation, mucositis, headache, and abdominal pain. It is important to promote the detection, collection, reporting, assessment and treatment of ARD’s in children. It is necessary to promote the conduct further studies on pharmacovigilance with this type of treatments and to increase the duration of the studies.
文摘Objective:Almost all leukemia patients died,fortunately now with the advancement of medicine and science and with the advent of treatment Chemotherapy,Radiotherapy,and Surgical treatment 75%of patients with leukemia who need treatment for up to 5 years,live longer than patients with leukemia who do not receive treatment.On the one side,in our country,Afghanistan the number of incidents has increased recently,and on the other side,we do not have data at the national level.Therefore,the child health hospital administration considered the necessary and left me to research this case in the last 6 months of 2018.Methods:This is an observational descriptive study,which observed 10,293 patients that come to the pediatric internal which 300 patients who indicate leukemia,and 200 patients with acute lymphoblastic leukemia(ALL),who were admitted to the oncology service of Andhra Gandhi Child Health Hospital in 2018 the study took place.Results:Based on the age we detect less than one year’s 10(5%)patients,1-10 years old 150(75%)patients,and more than 10 years old 40(20%)patients.Based on sex,boys were 120(60%)patients and girls 80(40%)patients.Based on clinical findings,anemia 155(77.5%)patients,fever 130(65%)patients,bleeding 90(45%)patients,spleen thickness 88(44%)patients,liver thickness 73(36.6%)patients,lymph nodes thickness 70(35.55%)patients,great pains 66(33%)patients and nervous system disorders 38(19%)patients.Conclusion:We can say with great conviction that 200 patients out of 10,293 had acute lymphoblastic leukemia.Further studies with prospective nature are required to confirm this observation.
文摘MicroRNAs(miRNAs)are short noncoding RNAs that regulate the expression of genes by sequence-specific binding to mRNA to either promote or block its translation;they can also act as tumor suppressors(e.g.,let-7b,miR-29a,miR-99,mir-100,miR-155,and miR-181)and/or oncogenes(e.g.,miR-29a,miR-125b,miR-143-p3,mir-155,miR-181,miR-183,miR-196b,and miR-223)in childhood acute leukemia(AL).Differentially expressed miRNAs are important factors associated with the initiation and progression of AL.As shown in many studies,they can be used as noninvasive diagnostic and prognostic biomarkers,which are useful in monitoring early stages of AL development or during therapy(e.g.,miR-125b,miR-146b,miR-181c,and miR-4786),accurate classification of different cellular or molecular AL subgroups(e.g.,let-7b,miR-98,miR-100,miR-128b,and miR-223),and identification and development of new therapeutic agents(e.g.,mir-10,miR-125b,miR-203,miR-210,miR-335).Specific miRNA patterns have also been described for commonly used AL therapy drugs(e.g.,miR-125b and miR-223 for doxorubicin,miR-335 and miR-1208 for prednisolone,and miR-203 for imatinib),uncovering miRNAs that are associated with treatment response.In the current review,the role of miRNAs in the development,progression,and therapy monitoring of pediatric ALs will be presented and discussed.
文摘Background: B-cell Acute lymphoblastic leukemia (B-ALL) is a neoplasm of lymphoblasts which are of B-cell lineage typically composed of small to medium sized blast cells, moderately condensed to dispersed chromatin with scanty cytoplasm and inconspicuous nucleoli, involving the bone marrow and/or blood. Methods and materials: This is a prospective cross-sectional study in which 50 blood and/or bone marrow samples of newly diagnosed patients (B-ALL) were tested for immunophenotyping. All samples were prepared for surface and cytoplasmic markers including kappa and lambda human antibody for 10 minutes in dark place and then run by the Flow Cytometer. Results: 64% of the study populations were males and 36% were females. Cases were classified according to immunophenotype and the age into different subtypes and showed the following frequencies: Pro B-ALL (8%), early pre B-ALL (56%), common B-ALL (16%), Pre-B-ALL (14%) and Mature B-ALL (only 6%). Surface immunoglobulin was positive in 10% and negative in 90% of all patients, showing 100% positivity in mature B-ALL and totally negative in other subtypes. While cytoplasmic immunoglobulin was positive in 16% and negative in 84% of all patients and was positive in 100% of Pre-B-ALL and in 50% of mature B-ALL. Surface kappa was more expressed in mature B-ALL than lambda giving a ratio of 2:1, while cytoplasmic kappa:lambda was 6:1 in Pre-B-ALL. Conclusion: Kappa and lambda have important role in B-ALL classification which necessitates their presence in immunophenotyping of B-ALL.
基金VIVA-China Children's Cancer Foundation and Prof.Pui team.
文摘Venous thromboembolism(VTE)is a complication in children with acute lymphoblastic leukemia(ALL).The Chinese Children’s Cancer Group-ALL-2015 protocol was carried out in China,and epidemiology,clinical characteristics,and risk factors associated with VTE were analyzed.We collected data on VTE in a multiinstitutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019.First,VTE occurred in 159(2.08%)patients,including 90(56.6%)during induction therapy and 108(67.92%)in the upper extremities.T-ALL had a 1.74-fold increased risk of VTE(95%CI 1.08–2.8,P=0.022).Septicemia,as an adverse event of ALL treatment,can significantly promote the occurrence of VTE(P<0.001).Catheter-related thrombosis(CRT)accounted for 75.47%(n=120);and,symptomatic VTE,58.49%(n=93),which was more common in patients aged 12–18 years(P=0.023),non-CRT patients(P<0.001),or patients with cerebral thrombosis(P<0.001).Of the patients with VTE treated with anticoagulation therapy(n=147),4.08%(n=6)had bleeding.The VTE recurrence rate was 5.03%(n=8).Patients with VTE treated by non-ultrasoundguided venous cannulation(P=0.02),with residual thrombus(P=0.006),or with short anticoagulation period(P=0.026)had high recurrence rates.Thus,preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
