双Ph伴双der(9)急性B淋巴细胞白血病患者1例的遗传学分析

Genetic analysis of a case of B-acute lymphoblastic leukaemia with double Philadelphia chromosomes and double derivative chromosome9s

目的探讨1例罕见的双费城染色体(Ph)伴双der(9)急性B淋巴细胞白血病(B-ALL)患者的遗传学病因。方法选取2020年6月至上海闸新中西医结合医院就诊的1例双Ph伴双der(9)B-ALL患者为研究对象。采用骨髓形态学分析、流式免疫分型、G显带核型分析、荧光原位杂交(FISH)、基因检测以及染色体微阵列分析(CMA)等方法对患者不同阶段的骨髓样本进行检测和分析。结果患者初诊时骨髓形态学、流式免疫分型均支持B-ALL的诊断,其G显带核型为双Ph且疑似存在2条与22号染色体易位的9号染色体的超二倍体,BCR-ABL1融合基因阳性。复发时基因检测提示ABL1基因的激酶编码区存在c.944C>T杂合变异,FISH证实2条9号染色体上均存在ABL1-BCR融合信号,CMA显示9号染色体嵌合纯合比例约为40%,22号染色体嵌合重复比例约为43%。结论本例患者双der(9)约在40%的细胞中完全同源,其产生机制可能与双Ph相同,可归因于有丝分裂时发生的染色体未分离。

ObjectiveTo explore the genetic basis for a rare case of acute B-lymphocytic leukemia(BALL)with double Philadelphia chromosomes(Ph)and double derivative chromosome 9s[der(9)J.Methods A patient with double Ph and double der(9)B-ALL who presented at Shanghai Zhaxin Intergrated Traditional Chinese and Western Medicine Hospital in June 2020 was selected as the subject.Bone marrow morphology,flow cytometry,G-banding karyotyping,fluorescence in situ hybridization(FISH),genetic testing and chromosomal microarray analysis(CMA)were used to analyze bone marrow samples from the patient at various stages.ResultsAt initial diagnosis,the patient's bone marrow morphology and flow immunotyping have both supported the diagnosis of B-ALL.G-banded karyotyping of the patient indicated double Ph,in addition with hyperdiploid chromosomes involving translocations between chromosomes 9 and 22.BCR-ABLl fusion gene was positive.Genetic testing at the time of recurrence revealed presence of a heterozyous c.944C>T variant in the kinase region of the ABLl gene.FISH showed a signal for ABL1-BCR fusion on both chromosome 9s.CMA showed that the mosaicism homozygosity ratio of chromosome 9 was about 40%,and the mosaicism duplication ratio of chromosome 22 was about 43%.Conclusion Since both der(9)homologs was seen in 40%of cells,the possible mechanism for the double der(9)in this patient may be similar to that of double Ph,which might have resulted from non-disjunction during mitosis in the Ph chromosome-positive cell clone.