20例t(8;21)复杂变异易位急性髓系白血病患者的临床和实验室研究

摘要

本研究总结分析t(8;21)复杂变异易位急性髓系白血病(AML)的形态学、免疫学、遗传学、分子生物学(MICM)分型,酪氨酸激酶相关基因突变和临床特点.对我院收治的20例初诊t(8;21)复杂变异易位AML进行了总结分析和随访,了解临床一般情况、形态学、免疫分型、染色体核型及治疗、生存情况,分析这一类疾病的基本特征.采用基因组DNA聚合酶链反应后桑格测序,对13例患者进行了酪氨酸激酶相关基因突变(C-KIT、FLT3-ITD、FLT3-TKD、JAK2V617F)的检测.结果表明:①本组20例t(8;21)复杂变异易位AML占同期t(8;21) AML的2.4％,其中M11例、M217例、M42例.13例行流式细胞术检测分析发现,10例为髓系表达,3例为髓系伴淋系表达.细胞遗传学检测显示额外受累的染色体断裂位点有16种:(lp22、1p32、2q35、2q14、3p25、5q13、6p22、7q21、llq11、1lql3、12q14、12q24、12p12、14q32、15p13、20q12).②13例患者中4例检测出C-KIT基因突变,且均为17号外显子突变,1例检测出JAK2 V617F基因突变,13例均未检测出FLT3基因突变.突变组患者经1个疗程诱导化疗后仅1例获得完全缓解(CR),CR率为20％,中位无复发生存时间(RFS)为6.5个月,中位总生存期(OS)为8.9个月;未突变组患者经1个疗程诱导化疗后6例获得CR,CR率为75％,中位RFS为26.6个月,中位OS为27.7个月.结论:t(8;21)复杂变异易位AML与典型t(8;21)AML的临床和实验室特点是相似的,但酪氨酸激酶相关基因突变的存在对患者的诱导化疗缓解率和长期生存具有重要的影响.%This study was aimed to summarize and analyze the morphology,immunophenotype,cytogenetics,molecular biology (MICM),tyrosine kinase(TK) gene mutations and clinical features of acute myeloid leukemia(AML) with complex variant of t(8;21).A retrospective study was performed for 20 AML patients with complex variant of t (8 ;21) in our hospital from January 1994 to April 2012,including analysis of clinical feature,immunophenotype,chromosome karyotype,treatment regimen,as well as the overall survival(OS) and relapse-free survival(RFS).Mutations of C-KIT,FLT3-ITD,FLT3-TKD and JAK2V617F were detected by genomic DNA PCR and the sequencing was performed in 13 AML patients with complex variant of t (8;21).The results showed that (1) the incidence of 20 AML patietns with complex variant of t(8; 21) was 2.4％ of total t(8; 21) AML patients.In 20 AML patients with complex variant of t(8;21),1 case was M1,17 cases were M2,2 cases were M4; 10 cases were myeloid phenotype and the other 3 were myeloid plus lymphoid phenotype.There were 16 kinds of cytogenetics additional involvement of chromosomal breakpoints:lp22,1p32,2q35,2q14,3p25,5q13,6p22,7q21,llq11,1lql3,12q14,12q24,12p12,14q32,15p13,20q12.(2) C-KIT aberrations were detected in 30.8％ cases,all mutated in exon 17 (mutkit 17),only 1 case had JAK2V617F mutation.The result of FLT3 mutation screenings in AML patients with complex variant of t(8; 21) was negative.Of 5 patients with gene mutations,1 patient (20％) achieved complete remission(CR),the median RFS and median OS time were 6.5 months and 8.9 months respectively.Of the 8 patients without gene mutations,6 patietns(75％) achieved CR; the median RFS and median OS time were 26.6 months and 27.7 months respectively.It is concluded that the AML patients with complex variant of t(8 ;21) shows typical features of t(8 ;21) AML,but the existence of the tyrosine kinase-related gene mutation has important implications on remission rate and long-term survival of patients treated by induction chemotherapy.