MLL-AF6、MLL-AF9及MLL-AF10与急性髓系白血病的临床研究

发布时间：2018-07-26 14:19

【摘要】：目的通过分析t(6;11)(q27;q23)/MLL-AF6、t(9;11)(p22;q23)/MLL-AF9及t(10;11)(p12;q23)/MLL-AF10融合基因的急性髓系白血病(acute myeloid leukemia, AML)的临床特点,探讨MLL-AF6、MLL-AF9及MLL-AF10融合基因与急性髓系白血病的临床关系。方法对初治的急性白血病患者的临床及实验室资料进行分析,其中选取分别表达MLL-AF6、MLL-AF9及MLL-AF10融合基因的急性髓系白血病患者作为临床观察对象。利用多重巢式反转录-聚合酶链反应检测患者治疗前、治疗后、造血干细胞移植前、造血干细胞移植后MLL-AF6、MLL-AF9及MLL-AF10融合基因的动态变化,分析患者临床特征、免疫表型、细胞遗传学、患者首次诱导治疗后完全缓解率、总体生存率、造血干细胞移植效果与患者预后的关系。结果 1)2008年2月至2015年1月住院病人初次诊断为急性白血病的患者827例,其中AML患者499例,表达MLL-AF6融合基因的AML患者13例、表达MLL-AF9融合基因的AML患者17例、表达MLL-AF10融合基因的AML患者11例。2)表达MLL-AF6、MLL-AF9及MLL-AF10融合基因的急性髓系白血病患者分别各占急性白血病的1.6%(13/827)、2.1%(17/827)、1.3%(11/827),分别占急性髓系白血病的2.6%(13/499)、3.4%(17/499)、2.2%(11/499)。3)所有分别表达MLL-AF6、MLL-AF9及MLL-AF10融合基因的急性髓系白血病患者的白血病FAB分型：M0 3例7.3%(3/41),Ml 5例12.3%(5/41),M27例17.1%(7/41),M4 10例24.4%(10/41),M5 16例39.0%(16/41),以M4/M5为主(63.4%,26/41)。4)41例入组患者中有23例患者初诊时白细胞计数50×109/L,其中12例白细胞计数100×109/L；25例患者发病时伴有肝脾淋巴结的肿大；高表达的细胞表面抗原CD33 90.2%(37/41)、CD34 70.7%(29/41)、CD15 70.7%(29/41)、CD11b 68.2% (28/41)、CD64 53.7%(22/41)、CD14 46.3%(19/41)、CD13 34.1%(14/41)、CD117 29.2%(12/41).5)41例入组患者中首次化疗后完全缓解率63.4%(26/41),总体生存率39.0%(16/41),经单纯化疗治疗的患者23例,平均生存时间为17.1个月,至随访结束之日仍存活的患者5例,存活率21.7%(5/23)；经造血干细胞移植治疗的患者18例,平均生存时间为24.7个月,至随访结束之日仍存活的患者11例,存活率61.1%(11/18)。经单纯化疗治疗的患者CR后有7例半年内复发,复发率53.8%(7/13),经造血干细胞移植治疗的患者移植后有5例半年内复发,复发率38.5%(5/13)。6)在本研究中应用多重巢式反转录-聚合酶链反应检测41例入组患者治疗前、治疗后、造血干细胞移植前、造血干细胞移植后MLL-AF6、MLL-AF9及MLL-AF10融合基因动态变化,14例患者治疗后融合基因检测持续阴性,27例患者治疗后融合基因检测非持续阴性,其中2例患者融合基因检测阴性阳性交替出现,10例患者融合基因检测阴性阳性交替后持续阳性；且该12例患者中7例经单纯化疗治疗后半年内复发,复发前融合基因检测为阳性,5例经造血干细胞移植治疗后半年内复发,复发前融合基因检测为阳性；15例患者融合基因检测治疗前后持续表达阳性(包括2例表达MLL-AF6融合基因的急性髓系白血病失访的患者)。结论 1)表达MLL-AF6、MLL-AF9及MLL-AF10融合基因的AML患者在急性白血病中发病率低。2)表达MLL-AF6、MLL-AF9及MLL-AF10融合基因的AML患者在AML-M4/M5中发生率高。3)表达MLL-AF6、MLL-AF9及MLL-AF10融合基因的AML患者多表达造血干细胞/祖细胞及单核系统相关表面抗原。4)表达MLL-AF6、MLL-AF9及MLL-AF10融合基因的AML患者发病时常伴有高白细胞、器官浸润,且治疗效果差,易复发,预后差。5)造血干细胞移植可改善患者预后,延长患者生存期。6)应用多重巢式反转录-聚合酶链反应检测患者治疗前后及造血干细胞移植前后融合基因的动态变化可在一定程度上帮助判断患者复发及预后。
[Abstract]:Objective to explore the clinical relationship between T (6; 11) (q27; q23) /MLL-AF6, t (9; 11) (P22; q23) /MLL-AF9 and t (p12; q23) /MLL-AF10 fusion gene in acute myeloid leukemia. The clinical and laboratory data were analyzed, in which the patients with acute myeloid leukemia which expressed MLL-AF6, MLL-AF9 and MLL-AF10 fusion genes were selected as clinical objects. The multiple nested reverse transcription polymerase chain reaction was used to detect the patients before, after the treatment, after the hematopoietic stem cell transplantation, after the hematopoietic stem cell transplantation, MLL-AF6, MLL- The dynamic changes of AF9 and MLL-AF10 fusion genes, analysis of patients' clinical characteristics, immunophenotype, cytogenetics, the total remission rate after the first induction of treatment, the overall survival rate, the relationship between the effect of hematopoietic stem cell transplantation and the prognosis of the patients. Results 1) 827 patients were first diagnosed as acute leukemia from February 2008 to January 2015. Of the 499 patients with AML, 13 cases of AML expressed MLL-AF6 fusion gene, 17 cases of AML expressing MLL-AF9 fusion gene, 11.2 of AML patients expressing MLL-AF10 fusion gene, and 1.6% (13/827), 2.1% (13/827), 1.3% (1.3%), respectively) of acute myeloid leukemia patients with MLL-AF9 and MLL-AF10 fusion genes, respectively. 2.6% (13/499), 3.4% (17/499), 2.2% (11/499).3) of acute myeloid leukemia, respectively, all of the acute myeloid leukemia patients expressing MLL-AF6, MLL-AF9 and MLL-AF10 fusion genes were classified as M0 3 7.3% (3/41), Ml 5 cases 12.3% (5/41), 17.1% 24.4% (24.4%), 16 39% (63.) and 63. (63.) 4%, 26/41).4) of the 41 patients, there were 23 cases of leukocyte count 50 x 109/L at first diagnosis, 12 cases of leukocyte count 100 x 109/L, 25 patients with liver and spleen lymph node enlargement, high expression of cell surface antigen CD33 90.2% (37/41), CD34 70.7% (29/41), CD15 70.7% (29/41), CD11b 68.2% (28/41), 53.7% 46.3% (19/41), CD13 34.1% (14/41), CD117 29.2% (12/41).5) complete remission rate of 63.4% (26/41), total survival rate of 39% (16/41) after first chemotherapy in 41 patients, 23 patients treated with simple chemotherapy, with an average survival time of 17.1 months, 5 cases still surviving on the day of follow-up, and 21.7% (5/23) survival rate, and hematopoietic stem cell migration. The average survival time of the 18 patients was 24.7 months, and the survival rate of the patients was 24.7 months to the end of the follow-up. The survival rate was 61.1% (11/18). After the chemotherapy alone, 7 cases had a recurrence within half a year and the recurrence rate was 53.8% (7/13). After the transplantation of hematopoietic stem cells, there were 5 cases of relapse in half a year, and the recurrence rate 38.5% (5/13).6). In this study, the multiple nested reverse transcription polymerase chain reaction was used to detect the dynamic changes of the MLL-AF6, MLL-AF9 and MLL-AF10 fusion genes before the hematopoietic stem cell transplantation and the fusion gene after the hematopoietic stem cell transplantation before the treatment of 41 patients. After the treatment, the fusion gene was detected in 14 patients, and the fusion gene was not sustained after treatment in 27 patients. Negative, of which 2 patients had negative fusion gene test negative positive alternately, and 10 patients were positive after fusion gene negative positive alternation, and 7 of the 12 patients had relapse within half a year after simple chemotherapy, positive fusion gene detection before relapse, 5 cases relapsed in half a year after hemopoietic stem cell transplantation, and relapse before relapse. Gene detection was positive; 15 patients were positive before and after fusion gene detection (including 2 patients with acute myeloid leukemia expressing MLL-AF6 fusion gene). Conclusion 1) expression of MLL-AF6, AML patients with MLL-AF9 and MLL-AF10 fusion gene in acute leukemia with low incidence of.2) expressed MLL-AF6, MLL-AF9 and MLL-AF10 melting. The incidence of AML in AML-M4/M5 is high.3) expression of MLL-AF6. The AML patients with MLL-AF9 and MLL-AF10 fusion genes express hematopoietic stem cell / progenitor cells and mononuclear related surface antigen.4) to express MLL-AF6. The AML patients with MLL-AF9 and MLL-AF10 fusion gene often have high white cells and organ infiltration, and the treatment effect is poor and easy. Recurrence and poor prognosis.5) hematopoietic stem cell transplantation can improve the patient's prognosis and prolong the patient's survival time (.6). The application of multiple nested reverse transcription polymerase chain reaction (PCR) to detect the dynamic changes of the fusion gene before and after the transplantation of the hematopoietic stem cells can help to determine the recurrence and prognosis of the patients to a certain extent.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R733.71

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