The proliferative response of T-cells to autolo-gous non-T-cells is referred to as the autologous mixed lymphocyte reaction (AMLR). Recent studies have suggested that AMLR represents a mechanism of immune regulation i...The proliferative response of T-cells to autolo-gous non-T-cells is referred to as the autologous mixed lymphocyte reaction (AMLR). Recent studies have suggested that AMLR represents a mechanism of immune regulation in vivo. We investigated AMLR in patients with acute- and chronic myeloid leukemia (AML and CML). AMLR was found to be significantly depressed (P<0.001) in AML patients (n=17, cpm=532±95) and CML patients (n=13, cpm=688±99) when compared with that of their healthy HLA-identical siblings serving as controls (n=17, cpm=4152±619 and n=13 cpm=4086±421, respectively). In order to understand the cellular basis of the defective AMLR in patients with AML end CML, we performed mitogen-treated T-cell cultures analysis of T-cell subsets and HLA-Ⅱ antigen detection on monocytes. The results indicated that the defect of AMLR in patients resided at the stimulator monocyte level rather than at the responder T-cell level. Enumeration of monocytes reactive with monoclonal antibody Tu22, which recognizes determinants of HLA-DQ, demonstrated that ML patients had a significantly decreased (P<0.091) number of circulating Tu22+ monocytes when compared with normal controls. These studies suggest that a deficiency of HLA-DQ+ monocytes contributes to the depression of AMLR in ML and possibly underlies the abnormalities of immune response present in this disease.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
目的:分析急性髓系白血病(AML)跨系抗原表达的临床特征及其预后意义,以便对此类患者进行预后分层,为建立个体化的治疗提供指导。方法:用流式细胞术对227例初发AML患者(M3除外)进行免疫分型,以CD7^-CD56^-CD19^-的AML为对照,比较CD7^+组...目的:分析急性髓系白血病(AML)跨系抗原表达的临床特征及其预后意义,以便对此类患者进行预后分层,为建立个体化的治疗提供指导。方法:用流式细胞术对227例初发AML患者(M3除外)进行免疫分型,以CD7^-CD56^-CD19^-的AML为对照,比较CD7^+组、CD56^+组、CD19^+组及对照组间的临床特征、治疗反应和生存情况。结果:CD56^+AML、CD7^+AML和CD19^+AML检出率分别为15.9%、25.1%和11.0%。3个组的发病年龄,原始细胞比例,白细胞计数,血红蛋白含量,血小板计数,MDS继发的AML分布与对照组无统计学差异。CD56^+AML首次化疗后完全缓解(CR)率和累积CR率均低于对照组(20.0%vs 58.1%,P=0.0099;73.3%vs 87.5%,P=0.04),取得CR的中位时间长于对照组(118 d vs 46 d,P=0.04),无进展生存期(PFS)和总体生存期(OS)低于对照组(245 d vs 580 d,P=0.037;494 dvs 809 d,P=0.04)。CD19^+AML首次化疗后CR率、累积CR率均高于对照组(75.0%vs 58.1%,P=0.46;100%vs 87.5%,P=0.02),取得CR的中位时间明显少于对照组(28 d vs 46 d,P=0.02),PFS及OS较对照组有延长趋势(P=0.13;P=0.07),至末次随访中位PFS及OS尚未达到。CD7^+AML首次化疗后CR率、累积CR率、取得CR中位时间与对照组比较均未取得统计学差异(53.1%vs 58.1%,P=0.67;87.1%vs 87.5%,P=0.44;50 d vs 46 d,P=0.44),PFS和OS与对照组比也无差异。结论:CD56^+AML患者治疗反应差,诱导缓解后易复发,总体生存期短,应在治疗之初选择更强的化疗方案或联合多种治疗手段,并缩短该类患者的MRD检测周期,以期早期发现残留白血病细胞并早期干预。CD19^+AML患者治疗反应好,不易复发,总体生存期长,对此类患者应避免过度治疗。异常表达CD7抗原不是AML预后不良因素。展开更多
文摘The proliferative response of T-cells to autolo-gous non-T-cells is referred to as the autologous mixed lymphocyte reaction (AMLR). Recent studies have suggested that AMLR represents a mechanism of immune regulation in vivo. We investigated AMLR in patients with acute- and chronic myeloid leukemia (AML and CML). AMLR was found to be significantly depressed (P<0.001) in AML patients (n=17, cpm=532±95) and CML patients (n=13, cpm=688±99) when compared with that of their healthy HLA-identical siblings serving as controls (n=17, cpm=4152±619 and n=13 cpm=4086±421, respectively). In order to understand the cellular basis of the defective AMLR in patients with AML end CML, we performed mitogen-treated T-cell cultures analysis of T-cell subsets and HLA-Ⅱ antigen detection on monocytes. The results indicated that the defect of AMLR in patients resided at the stimulator monocyte level rather than at the responder T-cell level. Enumeration of monocytes reactive with monoclonal antibody Tu22, which recognizes determinants of HLA-DQ, demonstrated that ML patients had a significantly decreased (P<0.091) number of circulating Tu22+ monocytes when compared with normal controls. These studies suggest that a deficiency of HLA-DQ+ monocytes contributes to the depression of AMLR in ML and possibly underlies the abnormalities of immune response present in this disease.
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.
文摘目的:分析急性髓系白血病(AML)跨系抗原表达的临床特征及其预后意义,以便对此类患者进行预后分层,为建立个体化的治疗提供指导。方法:用流式细胞术对227例初发AML患者(M3除外)进行免疫分型,以CD7^-CD56^-CD19^-的AML为对照,比较CD7^+组、CD56^+组、CD19^+组及对照组间的临床特征、治疗反应和生存情况。结果:CD56^+AML、CD7^+AML和CD19^+AML检出率分别为15.9%、25.1%和11.0%。3个组的发病年龄,原始细胞比例,白细胞计数,血红蛋白含量,血小板计数,MDS继发的AML分布与对照组无统计学差异。CD56^+AML首次化疗后完全缓解(CR)率和累积CR率均低于对照组(20.0%vs 58.1%,P=0.0099;73.3%vs 87.5%,P=0.04),取得CR的中位时间长于对照组(118 d vs 46 d,P=0.04),无进展生存期(PFS)和总体生存期(OS)低于对照组(245 d vs 580 d,P=0.037;494 dvs 809 d,P=0.04)。CD19^+AML首次化疗后CR率、累积CR率均高于对照组(75.0%vs 58.1%,P=0.46;100%vs 87.5%,P=0.02),取得CR的中位时间明显少于对照组(28 d vs 46 d,P=0.02),PFS及OS较对照组有延长趋势(P=0.13;P=0.07),至末次随访中位PFS及OS尚未达到。CD7^+AML首次化疗后CR率、累积CR率、取得CR中位时间与对照组比较均未取得统计学差异(53.1%vs 58.1%,P=0.67;87.1%vs 87.5%,P=0.44;50 d vs 46 d,P=0.44),PFS和OS与对照组比也无差异。结论:CD56^+AML患者治疗反应差,诱导缓解后易复发,总体生存期短,应在治疗之初选择更强的化疗方案或联合多种治疗手段,并缩短该类患者的MRD检测周期,以期早期发现残留白血病细胞并早期干预。CD19^+AML患者治疗反应好,不易复发,总体生存期长,对此类患者应避免过度治疗。异常表达CD7抗原不是AML预后不良因素。
