两种异常核型髓系肿瘤的基因突变及临床相关性分析

doi:10.3969/j.issn.1004-616x.2021.04.010

摘要/Abstract

摘要： 目的：分析伴有+1，der（1；7）（p10；q10）[以下简称der（1；7）]和-7/7q-这两种异常核型髓系肿瘤患者的临床特征及实验室检查结果、基因突变与预后生存的差异，并指导其临床诊断、治疗及预后判断。方法：回顾性分析2013年1月—2020年11月潍坊市人民医院21例伴有der（1；7）或-7/7q-异常核型的骨髓增生异常综合征（MDS）、急性髓系白血病（AML）和骨髓增殖性疾病（MPN）患者的临床资料，分为der（1；7）组和-7/7q-组，采集患者的骨髓液标本，应用下一代测序检测与疾病相关的38个基因突变，分析核型异常与实验室检查结果、基因突变特点、疾病亚型和生存时间的关系，并比较两种核型的差异。结果：21例患者中，der（1；7）患者以男性为主（P=0.024），der（1；7）患者较-7/7q-患者的血小板计数显著下降（P=0.036）、C反应蛋白（CRP）较高（P=0.029）。免疫分型无明显差异（χ²=0.078，P=1.000）。15例（71.4%）患者共检出13种基因的37个突变，人均检出（1.76±1.02）个突变。der（1；7）患者中RUNX1（21.4%）、IDH1/IDH2（21.4%）、JAK2（21.4%）基因突变频率较高，-7/7q-患者中SETBP1（17.4%）、TET2（17.4%）、ASXL1（13%）、U2AF1（13%）、DNMT3A（13%）基因突变频率较高。两组的基因突变组成差异有统计学意义（P=0.012），基因突变与核型异常之间存在显著相关性（r_s=0.522，P=0.001）。der（1；7）组患者的总生存期（OS）、中位OS均较-7/7q-组缩短（P=0.045，HR=2.844）。der（1；7）组患者中RUNX1基因突变型中位OS短于野生型（P=0.435）。-7/7q-组患者中ASXL1突变型较野生型OS缩短（P=0.018）。结论：der（1；7）和-7/7q-核型异常的髓系肿瘤是两种相互独立的疾病亚型，二者在实验室检测结果、基因突变和临床转归方面存在显著差异。

关键词: 细胞遗传学, der (1;7), 异常核型, 骨髓增生异常综合征, 急性髓系白血病, 基因突变

Abstract: OBJECTIVE: To investigate clinical features, laboratory findings and survival in myeloid leukemia patients who had +1,der (1;7)(p10;q10) or -7/7q- abnormal karyotypes,and to guide their clinical diagnosis,treatment and prognosis. METHODS: From January 2013 to November 2020,clinical data of 21 patients with the mentioned karyotype abnormalities,including myelodysplastic syndrome (MDS),acute myeloid leukemia (AML) and myeloproliferative neoplasm (MPN),were analyzed. Bone marrow fluid samples were collected and used to detect 38 disease-related gene mutations using a next generation sequencing method and collected data were evaluated to achieve our objectives. RESULTS: Among the 21 patients,those with der(1;7) were predominantly male (P=0.024),had significantly lower platelet counts (P=0.036) and higher CRP (P=0.029) than those with -7/7q-. Immunophenotypes of the two groups were similar (χ²=0.078,P=1.000). There were 37 mutations in 13 genes among 15 patients (71.4%). The mutation frequencies of RUNX1 (21.4%),IDH1/IDH2 (21.4%) and JAK2 (21.4%) were higher in patients with der(1;7),and SETBP1 (17.4%),TET2 (17.4%),ASXL1 (13%),U2AF1 (13%) and DNMT3A (13%) were higher in patients with 7/7q- than the comparison groups. There was significant differences in gene mutation compositions between the two groups (P=0.012),and significant correlations between gene mutations and karyotype abnormalities (r_s=0.522,P=0.001). The der(1;7) patients had significantly shorter overall and median survival durations than the -7/7q- patients (P=0.045,HR=2.844). In the der(1;7) patients,the median survival times of those with the RUNX1 mutation were shorter than those with the wild type (P=0.435). The median survival and total survival times for those with the ASXL1 mutation were significantly shorter than those with the wild type among the 7/7q- patients (P=0.018).CONCLUSION: Our data indicate that myeloid leukemia with the two abnormal karyotypes:der(1;7) or -7/7q-,were independent disease subtypeswith significant differences in laboratory findings,gene mutations and clinical outcomes.

Key words: cytogenetics, der(1;7), abnormal karyolypes, myelodysplastic syndrome, acute myelogenous leukemia, genetic mutations

中图分类号:

R551.3

徐启璐, 高慧, 冉学红, 王军军, 张俊英, 刘丽萍. 两种异常核型髓系肿瘤的基因突变及临床相关性分析[J]. 癌变·畸变·突变, 2021, 33(4): 296-301,306.

XU Qilu, GAO Hui, RAN Xuehong, WANG Junjun, ZHANG Junying, LIU Liping. Gene mutation and clinical correlation analyses of myeloid leukemia with abnormal karyotypes[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 296-301,306.

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