MLL-AF6融合基因阳性急性髓系白血病的临床特征及预后  

Clinical characteristics and prognosis of MLL-AF6 positive patients with acute myeloid leukemia

作　　者：张梅香[1] 史文芝[2] 刘建新 王春键 李燕 王蔚 江滨 ZHANG Mei-xiang;SHI Wen-zhi;LIU Jian-xin;WANG Chun-jian;LI Yan;WANG Wei;JIANG Bin(Department of Hematology,Peking University International Hospital,Beijing 102206,China;Heping Hospital Affiliated to Changzhi Medical College,Changzhi 046000,Shanxi,China)

机构地区：[1]北京大学国际医院血液科,北京102206 [2]山西长治医学院附属和平医院血液科,山西长治046000

出　　处：《北京大学学报（医学版）》2021年第5期915-920,共6页Journal of Peking University:Health Sciences

摘　　要：目的:探讨MLL-AF6融合基因阳性的急性髓系白血病(acute myeloid leukemia,AML)患者的临床特征和预后。方法:回顾分析11例初治MLL-AF6阳性AML患者的临床和实验室资料,复习文献,总结该类疾病的临床特征及预后。结果:11例患者中男6例,女5例,中位年龄36岁,急性白血病的分型诊断标准FAB分型(French-American-British classification systems)M56例,M45例。起病症状为牙龈肿痛6例,发热5例,初诊时中位白细胞计数55.5×10^(9)/L,免疫分型可见髓系细胞、单核细胞系统及干细胞系列抗原表达。MLL-AF6融合基因水平(实时定量PCR法)为14.2%~214.5%,6/11例(54.5%)合并EVI1基因高表达。4例患者二代测序检测出合并KRAS、TET2、ASXL1、TP53、DNMT3A及FLT3-ITD基因突变。染色体G显带检查,2例为t(6;11)(q27,q23)伴复杂核型异常,4/9例(44.4%)伴有+8异常,2例为正常核型。给予患者常规诱导化疗,达到完全缓解者8/11例(72.7%),3例患者原发耐药。8例完全缓解的患者中,2例达到微小残留病(minimal residual disease,MRD)阴性,中位完全缓解的持续时间为4.5个月。2例MRD阳性及3例难治复发患者接受了异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT),后均死于白血病进展。随访至2019年12月1日,2例存活,9例死亡,中位生存时间9个月。结论:MLL-AF6融合基因阳性AML多为年轻患者,FAB分型以M4、M5居多,常以发热起病,白细胞增高,可伴器官浸润,合并EVI1基因高表达多见。本病常规化疗的缓解率不低,但达到分子学缓解困难,极易出现早期复发,持续分子学阴性状态下尽早行allo-HSCT可能获得长期完全缓解。Objective:To investigate the clinical features and prognosis of acute myeloid leukemia(AML)patients with the mixed lineage leukemia(MLL)gene rearrangements AF6(MLL-AF6)positive.Methods:In the study,11 patients who were newly diagnosed with MLL-AF6 positive AML were analyzed retrospectively,related literature was reviewed to clarify the clinical features and prognosis of MLL-AF6 positive patients.Results:Among the 11 patients,there were 6 males and 5 females,with a median age of 36 years.Six patients were diagnosed with AML M5 and five with M4 according to FAB classification(French-American-British classification systems).Gingival swelling and pain occurred in 6 cases and fever occurred in 5 cases.At first diagnosis,the median white blood cells were 55.5×10^(9)/L.Immunotype showed the expression of myeloid/monocyte and early stem cell series antigens.The expression level of MLL-AF6 fusion gene(real-time quantitative PCR)was 14.2%-214.5%,and 6/11 cases(54.5%)were associated with high EVI1 gene expression.Mutations of KRAS,TET2,ASXL1,TP53,DNMT3A,and FLT3-ITD were detected by next generation sequencing(NGS)in 4 patients.Chromosome G banding examination showed that 2 cases were t(6;11)(q27,q23)with complex karyotype abnormality,4 cases with+8 abnormality and 2 cases with normal karyotype.Hematological complete remission(CR)was achieved in 8/11 patients(72.7%)after conventional induction chemotherapy,and primary drug resistance was observed in 3 patients.Two of the eight patients with CR were negative for minimal residual disease(MRD),with a median CR duration of 4.5 months.Two patients with positive MRD and three patients with refractory recurrence underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT),but all died due to leukemia progression.At the end of follow-up on December 1,2019,2 patients were alive and 9 died,with median survival time of 9 months.Conclusion:The AML patients with MLL-AF6 positive were mostly young,the majority of FAB types were M4 and M5,and most of the patients often had feve

关 键 词：白血病 髓系 基因融合 基因重排 MLL-AF6 疾病特征 预后 

分 类 号：R733.71[医药卫生—肿瘤]