【摘要】 目的 分析T细胞急性淋巴细胞白血病染色体碎裂化的发病率及相关遗传事件。方法 纳入T细胞急性淋巴细胞白血病患者32例，年龄23～61岁，平均年龄(26.49±8.49)岁。其中起源于早期前体T细胞(ETP)的急性淋巴细胞白血病14例，为ETP组；非ETP的急性淋巴细胞白血病18例，为non-ETP组。单核苷酸多态性阵列(SNPa)和全基因组测序(WGS)检测染色体碎裂化并分析与T细胞急性淋巴细胞白血病发生发展的相关遗传事件。结果 SNPa总计检测到249个基因组变异事件，其中有160个丢失，67个获得和22个拷贝中性杂合度损失。在ETP组中发现的基因组变异事件数量明显高于non-ETP组(P<0.05)。在32例患者中有9例检测到染色体碎裂化(28.13%),均为ETP组，并涉及两条(3例)、三条(4例)、四条(2例)染色体。染色体5、6、7、9、12和17经常受到影响。9例染色体碎裂化病例中主要的基因组变异基因包括SET-NUP214重排(5例)、SQSTM1-NUP214重排(1例)、TRB-HOXA重排(3例)。染色体碎裂化阳性病例的基因组变异事件发生率明显高于染色体碎裂化阴性病例(P<0.05)。相反，染色体碎裂化阴性病例中，基因组变异事件的发生率在ETP组和non-ETP组之间没有显著差异。结论 T细胞急性淋巴细胞白血病的染色体碎裂化发病率为28.13%,并且都是发生在ETP,染色体碎裂化相关的主要基因组变异事件是SET-NUP214、SQSTM1-NUP214、TRB-HOXA重排。更多还原

【Abstract】 Objective To count the incidence of chromosomal fragmentation in T-cell acute lymphoblastic leukemia and to perform an analysis of associated genetic events.Methods 32 patients with T-cell acute lymphoblastic leukemia with an age range of 23 to 61 years and a mean age of(26.49±8.49) years, were included.Among them, there were 14 cases of acute lymphoblastic leukemia originating from early precursor T cells(ETP) in the ETP group and 18 cases of non-ETP acute lymphoblastic leukemia in the non-ETP group.Single nucleotide polymorphism array(SNPa) and whole genome sequencing(WGS) were used to detect chromosomal fragmentation and analyze genetic events associated with the development of T-cell acute lymphoblastic leukemia.Results SNPa detected a total of 249 genomic variant events, with 160 losses, 67 gains and 22 copy-neutral loss of heterozygosity(cnLOH).The number of genomic variant events found in the ETP group was significantly higher than in the non-ETP group(P<0.05).Chromothripsis was detected in 9 of 32 patients(28.13%),all in the ETP group, and involved two(3),three(4),and four(2) chromosomes.Chromosomes 5,6,7,9,12,and 17 were frequently affected.the major genomic variant genes in the nine chromosomal fragmentation cases included SET-NUP214 rearrangement(five cases),SQSTM1-NUP214 rearrangement(one case),and TRB-HOXA rearrangement(three cases).The genomic variant events were significantly higher in chromosomal fragmentation-positive cases than in chromosomal fragmentation-negative cases(P<0.05).In contrast, the incidence of genomic variant events in chromosomal fragmentation-negative cases was not significantly different between the ETP and non-ETP groups.Conclusion The incidence of chromosomal fragmentation in T-cell acute lymphoblastic leukemia is 28.13% and all occurred in ETP,and the major genomic variant events associated with chromosomal fragmentation are SET-NUP214,SQSTM1-NUP214,and TRB-HOXA rearrangements.更多还原