Classical Philadelphia-negative myeloproliferative neoplasms(MPNs),i.e.,polycythemia vera,essential thrombocythemia,and primary/secondary myelofibrosis,are clonal disorders of the hematopoietic stem cell in which an u...Classical Philadelphia-negative myeloproliferative neoplasms(MPNs),i.e.,polycythemia vera,essential thrombocythemia,and primary/secondary myelofibrosis,are clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells occurs.MPNs are characterized by mutations in driver genes,the JAK2V617F point mutation being the most commonly detected genetic alteration in these hematological malignancies.Thus,JAK inhibition has emerged as a potential therapeutic strategy in MPNs,with ruxolitinib being the first JAK inhibitor developed,approved,and prescribed in the management of these blood cancers.However,the use of ruxolitinib has been associated with a potential risk of infection,including opportunistic infections and reactivation of hepatitis B.Here,we briefly describe the association between ruxolitinib treatment in MPNs and hepatitis B reactivation.展开更多
Acute myeloid leukemia(AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based ...Acute myeloid leukemia(AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based on somatic mutations, AML is still characterized by poor outcomes, with a 5-year survival rate of only 30%-40%, the majority of the patients dying due to AML relapse. Leukemia stem cells(LSC) are considered to be at the root of chemotherapeutic resistance and AML relapse. Although numerous studies have tried to better characterize LSCs in terms of surface and molecular markers, a specific marker of LSC has not been found, and still the most universally accepted phenotypic signature remains the surface antigens CD34+CD38- that is shared with normal hematopoietic stem cells. Animal models provides the means to investigate the factors responsible for leukemic transformation, the intrinsic differences between secondary post-myeloproliferative neoplasm AML and de novo AML, especially the signaling pathways involved in inflammation and hematopoiesis. However, AML proved to be one of the hematological malignancies that is difficult to engraft even in the most immunodeficient mice strains, and numerous ongoing attempts are focused to develop "humanized mice" that can support the engraftment of LSC. This present review is aiming to in-troduce the field of AML pathogenesis and the concept of LSC, to present the current knowledge on leukemic blasts surface markers and recent attempts to develop best AML animal models.展开更多
AIM To define clinical criteria to differentiate eosinophilic gastrointestinal disorder(Eo GD) in the esophagus. METHODS Our criteria were defined based on the analyses of the clinical presentation of eosinophilic eso...AIM To define clinical criteria to differentiate eosinophilic gastrointestinal disorder(Eo GD) in the esophagus. METHODS Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis(Eo E), subepithelial eosinophilic esophagitis(s Eo E) and eosinophilic esophageal myositis(Eo EM), identified by endoscopy, manometry and serum immunoglobulin E levels(s-Ig E), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples.RESULTS In five patients with Eo E, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with s Eo E and four with Eo EM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with Eo E and s Eo E with some variation, while Eo EM was associated with hypercontractile or hypertensive peristalsis, with elevated s-Ig E. Histology revealed the following eosinophils per high-power field values. Eo E = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; s Eo E = 3 in the epithelium and 35 in the subepithelium(conventional biopsy); Eo EM = none in the epithelium, 10.7 ± 11.7 in the subepithelium(conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria(peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to Eo E. Eotaxin-3, IL-5 and IL-13 were overexpressed in Eo E.CONCLUSION Based on clinical and histological data, we identified criteria, which differentiated between Eo E, s Eo E and Eo EM, and reflected a different pathogenesis between these esophageal Eo GDs.展开更多
文摘Classical Philadelphia-negative myeloproliferative neoplasms(MPNs),i.e.,polycythemia vera,essential thrombocythemia,and primary/secondary myelofibrosis,are clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells occurs.MPNs are characterized by mutations in driver genes,the JAK2V617F point mutation being the most commonly detected genetic alteration in these hematological malignancies.Thus,JAK inhibition has emerged as a potential therapeutic strategy in MPNs,with ruxolitinib being the first JAK inhibitor developed,approved,and prescribed in the management of these blood cancers.However,the use of ruxolitinib has been associated with a potential risk of infection,including opportunistic infections and reactivation of hepatitis B.Here,we briefly describe the association between ruxolitinib treatment in MPNs and hepatitis B reactivation.
基金Supported by The project Competitiveness Operational Programme(COP)A1.1.4.,No.P_37_798,Contract 149/26.10.2016(My SMIS2014+:106774)
文摘Acute myeloid leukemia(AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based on somatic mutations, AML is still characterized by poor outcomes, with a 5-year survival rate of only 30%-40%, the majority of the patients dying due to AML relapse. Leukemia stem cells(LSC) are considered to be at the root of chemotherapeutic resistance and AML relapse. Although numerous studies have tried to better characterize LSCs in terms of surface and molecular markers, a specific marker of LSC has not been found, and still the most universally accepted phenotypic signature remains the surface antigens CD34+CD38- that is shared with normal hematopoietic stem cells. Animal models provides the means to investigate the factors responsible for leukemic transformation, the intrinsic differences between secondary post-myeloproliferative neoplasm AML and de novo AML, especially the signaling pathways involved in inflammation and hematopoiesis. However, AML proved to be one of the hematological malignancies that is difficult to engraft even in the most immunodeficient mice strains, and numerous ongoing attempts are focused to develop "humanized mice" that can support the engraftment of LSC. This present review is aiming to in-troduce the field of AML pathogenesis and the concept of LSC, to present the current knowledge on leukemic blasts surface markers and recent attempts to develop best AML animal models.
基金Supported by JSPS Grants-in-Aid for Scientific Research,No.16K19332Takeda medical research grants
文摘AIM To define clinical criteria to differentiate eosinophilic gastrointestinal disorder(Eo GD) in the esophagus. METHODS Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis(Eo E), subepithelial eosinophilic esophagitis(s Eo E) and eosinophilic esophageal myositis(Eo EM), identified by endoscopy, manometry and serum immunoglobulin E levels(s-Ig E), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples.RESULTS In five patients with Eo E, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with s Eo E and four with Eo EM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with Eo E and s Eo E with some variation, while Eo EM was associated with hypercontractile or hypertensive peristalsis, with elevated s-Ig E. Histology revealed the following eosinophils per high-power field values. Eo E = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; s Eo E = 3 in the epithelium and 35 in the subepithelium(conventional biopsy); Eo EM = none in the epithelium, 10.7 ± 11.7 in the subepithelium(conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria(peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to Eo E. Eotaxin-3, IL-5 and IL-13 were overexpressed in Eo E.CONCLUSION Based on clinical and histological data, we identified criteria, which differentiated between Eo E, s Eo E and Eo EM, and reflected a different pathogenesis between these esophageal Eo GDs.
