Leukemia stem cells(LSCs),which constitute a minority of the tumor bulk,are functionally defined on the basis of their ability to transfer leukemia into an immunodeficient recipient animal.The presence of LSCs has bee...Leukemia stem cells(LSCs),which constitute a minority of the tumor bulk,are functionally defined on the basis of their ability to transfer leukemia into an immunodeficient recipient animal.The presence of LSCs has been demonstrated in acute lymphoblastic leukemia(ALL),of which ALL with Philadelphia chromosome-positive(Ph+).The use of imatinib,a tyrosine kinase inhibitor(TKI),as part of front-line treatment and in combination with cytotoxic agents,has greatly improved the proportions of complete response and molecular remission and the overall outcome in adults with newly diagnosed Ph+ ALL.New challenges have emerged with respect to induction of resistance to imatinib via Abelson tyrosine kinase mutations.An important recent addition to the arsenal against Ph+ leukemias in general was the development of novel TKIs,such as nilotinib and dasatinib.However,in vitro experiments have suggested that TKIs have an antiproliferative but not an antiapoptotic or cytotoxic effect on the most primitive ALL stem cells.None of the TKIs in clinical use target the LSC.Second generation TKI dasatinib has been shown to have a more profound effect on the stem cell compartment but the drug was still unable to kill the most primitive LSCs.Allogeneic stem cell transplantation(SCT) remains the only curative treatment available for these patients.Several mechanisms were proposed to explain the resistance of LSCs to TKIs in addition to mutations.Hence,TKIs may be used as a bridge to SCT rather than monotherapy or combination with standard chemotherapy.Better understanding the biology of Ph+ ALL will open new avenues for effective management.In this review,we highlight recent findings relating to the question of LSCs in Ph+ ALL.展开更多
Objective To evaluate the outcome of combination of intensive preconditioning regimen allo - HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia ( ALL) . Methods Between 2009 and 2010,...Objective To evaluate the outcome of combination of intensive preconditioning regimen allo - HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia ( ALL) . Methods Between 2009 and 2010,8 patients diagnosed as Ph + ALL received展开更多
We report one case of pediatric acute myeloid leukemia type 2（AML-M2） who presented with karyotypic aberration of trisomy 21 with the t（5;11） chromosomal translocation. The patient achieved complete remission afte...We report one case of pediatric acute myeloid leukemia type 2（AML-M2） who presented with karyotypic aberration of trisomy 21 with the t（5;11） chromosomal translocation. The patient achieved complete remission after two cycles of chemotherapy of daunorubicin, cytarabine and etoposide. Then, follow-up cytogenetic analysis from bone marrow cell cultures demonstrated a normal karyotype of 46, XY. After 9 years, the patient relapsed and the karyotypic abnormalities of trisomy 21 with t（5;11） reappeared. It was concluded that trisomy 21 with t（5; 11） is a new unfavorable cytogenetic aberration in AML-M2.展开更多
Objective: Acute myeloid leukemia (AML) is a heterogeneous, hematologic malignancy at which short survival may be seen. Our study aims to evaluate the effect of the neutrophil-to-lymphocyte ratio (NLR) on the course o...Objective: Acute myeloid leukemia (AML) is a heterogeneous, hematologic malignancy at which short survival may be seen. Our study aims to evaluate the effect of the neutrophil-to-lymphocyte ratio (NLR) on the course of the disease, response to therapy, and overall survival (OS). Materials and Methods: A total of 124 patients followed-up with the diagnosis of AML from 2016 to 2019 were retrospectively examined. Results: 69 of the cases (55.6%) were men and 55 (44.3%) were women. The average age at the time of diagnosis was 53.44 ± 30.3 years old. We determined the NLR as median 0.46 (0.16 - 1.1). In AML, 69 patients were responsive to the induction regimen (57.9%) while 46 patients were unresponsive (37.8%). 5 patients died before completing the regimen. D-dimer was found to be higher and fibrinogen was found to be lower in the responsive group. Lower OS was observed in cases of >60 years of age, male gender, non-APL AML, high NLR, and recurrence at diagnosis. Recurrences were detected in 23 patients (18.5%) and the median time to the recurrence was 416 (236 - 639) days. Fibrinogen level and the bone marrow blast ratio at the time of application were determined to be associated with recurrence. The median follow-up time was 856 (143 - 1276) days. Final condition analysis reveals that 74 patients (59.6%) are alive. Conclusion: We determined in our study that the NLR is effective on survival. Medical literature on this subject is scanty and prospective studies with large patient groups are needed.展开更多
The peripheral blood lymphocyte chromosomes in a case of 60Co γ rays accident were examined at 2.5h after exposure. The frequency of the dicentrics plus centric rings was 89% and exposure dose was estimated to be 4.7...The peripheral blood lymphocyte chromosomes in a case of 60Co γ rays accident were examined at 2.5h after exposure. The frequency of the dicentrics plus centric rings was 89% and exposure dose was estimated to be 4.78 (4.53～4.88) Gy. The examinations of lymphocyte chromosome aberration within follow-up 12α showed that the incidence of Dic+R reduced with lg regression (r = -0.9895). While the number of cells with stable aberration remained unchanged and showed a tendency to increase. During the period of leukemia, bone marrow cell chromosome aberrations were studied by method of G-banding. Of 13 cells observed, 4 cells belonged to normal karyotypes. Among 9 aberration cells, 12 aberrations were detected. The majority of which were classified as translocation, deletion and inversion. Numeric aberrations were-9,-12,-20,-22,-y. This case suggested that acute lymphocytic leukemia was induced after radiation accident.展开更多
文摘Leukemia stem cells(LSCs),which constitute a minority of the tumor bulk,are functionally defined on the basis of their ability to transfer leukemia into an immunodeficient recipient animal.The presence of LSCs has been demonstrated in acute lymphoblastic leukemia(ALL),of which ALL with Philadelphia chromosome-positive(Ph+).The use of imatinib,a tyrosine kinase inhibitor(TKI),as part of front-line treatment and in combination with cytotoxic agents,has greatly improved the proportions of complete response and molecular remission and the overall outcome in adults with newly diagnosed Ph+ ALL.New challenges have emerged with respect to induction of resistance to imatinib via Abelson tyrosine kinase mutations.An important recent addition to the arsenal against Ph+ leukemias in general was the development of novel TKIs,such as nilotinib and dasatinib.However,in vitro experiments have suggested that TKIs have an antiproliferative but not an antiapoptotic or cytotoxic effect on the most primitive ALL stem cells.None of the TKIs in clinical use target the LSC.Second generation TKI dasatinib has been shown to have a more profound effect on the stem cell compartment but the drug was still unable to kill the most primitive LSCs.Allogeneic stem cell transplantation(SCT) remains the only curative treatment available for these patients.Several mechanisms were proposed to explain the resistance of LSCs to TKIs in addition to mutations.Hence,TKIs may be used as a bridge to SCT rather than monotherapy or combination with standard chemotherapy.Better understanding the biology of Ph+ ALL will open new avenues for effective management.In this review,we highlight recent findings relating to the question of LSCs in Ph+ ALL.
文摘Objective To evaluate the outcome of combination of intensive preconditioning regimen allo - HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia ( ALL) . Methods Between 2009 and 2010,8 patients diagnosed as Ph + ALL received
文摘We report one case of pediatric acute myeloid leukemia type 2（AML-M2） who presented with karyotypic aberration of trisomy 21 with the t（5;11） chromosomal translocation. The patient achieved complete remission after two cycles of chemotherapy of daunorubicin, cytarabine and etoposide. Then, follow-up cytogenetic analysis from bone marrow cell cultures demonstrated a normal karyotype of 46, XY. After 9 years, the patient relapsed and the karyotypic abnormalities of trisomy 21 with t（5;11） reappeared. It was concluded that trisomy 21 with t（5; 11） is a new unfavorable cytogenetic aberration in AML-M2.
文摘Objective: Acute myeloid leukemia (AML) is a heterogeneous, hematologic malignancy at which short survival may be seen. Our study aims to evaluate the effect of the neutrophil-to-lymphocyte ratio (NLR) on the course of the disease, response to therapy, and overall survival (OS). Materials and Methods: A total of 124 patients followed-up with the diagnosis of AML from 2016 to 2019 were retrospectively examined. Results: 69 of the cases (55.6%) were men and 55 (44.3%) were women. The average age at the time of diagnosis was 53.44 ± 30.3 years old. We determined the NLR as median 0.46 (0.16 - 1.1). In AML, 69 patients were responsive to the induction regimen (57.9%) while 46 patients were unresponsive (37.8%). 5 patients died before completing the regimen. D-dimer was found to be higher and fibrinogen was found to be lower in the responsive group. Lower OS was observed in cases of >60 years of age, male gender, non-APL AML, high NLR, and recurrence at diagnosis. Recurrences were detected in 23 patients (18.5%) and the median time to the recurrence was 416 (236 - 639) days. Fibrinogen level and the bone marrow blast ratio at the time of application were determined to be associated with recurrence. The median follow-up time was 856 (143 - 1276) days. Final condition analysis reveals that 74 patients (59.6%) are alive. Conclusion: We determined in our study that the NLR is effective on survival. Medical literature on this subject is scanty and prospective studies with large patient groups are needed.
文摘The peripheral blood lymphocyte chromosomes in a case of 60Co γ rays accident were examined at 2.5h after exposure. The frequency of the dicentrics plus centric rings was 89% and exposure dose was estimated to be 4.78 (4.53～4.88) Gy. The examinations of lymphocyte chromosome aberration within follow-up 12α showed that the incidence of Dic+R reduced with lg regression (r = -0.9895). While the number of cells with stable aberration remained unchanged and showed a tendency to increase. During the period of leukemia, bone marrow cell chromosome aberrations were studied by method of G-banding. Of 13 cells observed, 4 cells belonged to normal karyotypes. Among 9 aberration cells, 12 aberrations were detected. The majority of which were classified as translocation, deletion and inversion. Numeric aberrations were-9,-12,-20,-22,-y. This case suggested that acute lymphocytic leukemia was induced after radiation accident.
文摘目的分析外周血T淋巴细胞亚群水平与急性髓系白血病(acute myeloid leukemia,AML)患者病理特征的关系及对化疗预后的预测价值。方法选取2017年4月至2022年4月北京航天总医院80例AML患者作为研究组,另选同期性别、年龄匹配的80例健康志愿者作为对照组。比较2组一般资料、外周血T淋巴细胞亚群(CD4^(+)/CD8^(+)、CD3^(+)、CD4^(+))水平,比较研究组不同病理特征患者化疗前外周血T淋巴细胞亚群水平。并比较研究组不同预后患者临床资料、外周血T淋巴细胞亚群水平,分析AML预后不良的影响因素,分析外周血T淋巴细胞亚群预测AML预后不良的价值。结果与对照组比较,研究组化疗前外周血CD4^(+)/CD8^(+)、CD3^(+)、CD4^(+)水平明显降低(P<0.05);研究组NPM1突变阳性、FMS样酪氨酸激酶受体3-内部串联重复(FLT3-ITD)突变阳性、危险分层为低中风险患者外周血CD4^(+)/CD8^(+)、CD3^(+)、CD4^(+)水平分别高于NPM1突变阴性、FLT3-ITD阴性、危险分层为高风险患者(P<0.05);研究组预后不良患者年龄、危险分层高风险占比高于预后良好患者,化疗前外周血CD4^(+)/CD8^(+)、CD4^(+)、CD3^(+)水平低于预后良好患者(P<0.05);年龄、危险分层、化疗前外周血CD4^(+)/CD8^(+)、CD3^(+)、CD4^(+)水平均为AML患者预后不良的影响因素(P<0.05);化疗前外周血CD4^(+)/CD8^(+)、CD3^(+)、CD4^(+)预测AML预后不良的曲线下面积(area under curve,AUC)分别0.702、0.738、0.759。结论AML患者外周血CD4^(+)/CD8^(+)、CD3^(+)、CD4^(+)水平降低,与NPM1突变、FLT3-ITD突变、危险分层有关,且在预测AML预后不良方面具有一定预测价值。
