急性淋巴细胞白血病融合基因表达特点分析

Characteristics of fusion gene expression in acute lymphoblastic leukemia

目的分析初诊急性淋巴细胞白血病(ALL)患者融合基因的表达情况,进一步探讨融合基因阳性患者的实验室检查特点。方法回顾性分析2016年9月至2020年12月天津见康华美医学诊断中心1994例初诊ALL患者的融合基因筛查结果,同时对表达不同融合基因患者的基因突变筛查结果、免疫表型特点及染色体核型结果进行系统分析。结果(1)1994例ALL患者,中位年龄为12岁(15 d至89岁)。44.3%(884/1994)的ALL患者检测到15种不同的融合基因,其表达呈现典型的“幂律分布”。(2)急性B淋巴细胞白血病(B-ALL)患者融合基因的阳性率显著高于急性T淋巴细胞白血病(T-ALL)患者(48.48%∶18.71%),B-ALL和T-ALL的融合基因分布具有重现性的特点,交叉少见。(3)融合基因的表达高峰分别出现在<1岁、3~5岁和35~44岁;儿童患者融合基因的种类明显多于成人;MLL-FG、TEL-AML1及BCR-ABL1分别是婴儿、儿童和成人患者最常见的融合基因。(4)融合基因阳性ALL患者以伴随信号通路相关基因突变为主,其中以NRAS和KRAS突变率最高;携带不同融合基因的B-ALL患者早期标记和B系标记表达有差异;BCR-ABL1阳性患者复杂核型检出率明显高于其他融合基因阳性患者。结论不同年龄及类型的ALL患者,其融合基因的表达特点明显不同;携带不同融合基因的ALL患者,突变基因、免疫表型及染色体核型特点也存在差异。

Objective To analyze the genetic landscape of 52 fusion genes in patients with de novo acute lymphoblastic leukemia(ALL)and to investigate the characteristics of other laboratory results.Methods The fusion gene expression was retrospectively analyzed in the 1994 patients with de novo ALL diagnosed from September 2016 to December 2020.In addition,their mutational,immunophenotypical and karyotypical profiles were investigated.Results In the 1994 patients with ALL,the median age was 12 years(from 15 days to 89 years).In the panel of targeted genes,15 different types of fusion genes were detected in 884 patients(44.33%)and demonstrated a Power law distribution.The frequency of detectable fusion genes in B-cell ALL was significantly higher than that in T-cell ALL(48.48%vs 18.71%),and fusion genes were almost exclusively expressed in B-cell ALL or T-cell ALL.The number of fusion genes showed peaks at<1 year,3-5 years and 35-44 years,respectively.More fusion genes were identified in children than in adults.MLL-FG was most frequently seen in infants and TEL-AML1 was most commonly seen in children,while BCR-ABL1 was dominant in adults.The majority of fusion gene mutations involved signaling pathway and the most frequent mutations were observed in NRAS and KRAS genes.The expression of early-stage B-cell antigens varied in B-cell ALL patients.The complex karyotypes were more common in BCR-ABL1 positive patients than others.Conclusion The distribution of fusion genes in ALL patients differs by ages and cell lineages.It also corresponds to various gene mutations,immunophenotypes,and karyotypes.