伴有e1a3型BCR-ABL且T315I突变的Ph染色体阳性成人急性淋巴细胞白血病1例并文献复习

Ph chromosome positive acute lymphoblastic leukemia patients with a e1a3 BCR-ABL fusion gene and T315I mutation:One case report and literature review

目的:通过分析1例具有e1a3型BCR-ABL融合基因的Ph染色体阳性成人急性淋巴细胞白血病(ALL)患者,结合文献回顾,阐述其临床和生物学特点。方法:采用骨髓细胞形态学及流式细胞术确定白血病诊断及免疫分型,常规染色体及荧光原位杂交技术检测细胞遗传学异常,实时荧光定量PCR(RQ-PCR)方法确定BCR-ABL融合基因类型及拷贝数,并进行系统的文献复习。结果:患者临床表现符合典型ALL特征,FISH检测核型结果示Ph染色体阳性。常规BCR-ABL分型试剂盒未检测出任何扩增曲线,进一步用BCR-ABL少见型融合基因检测试剂盒检测发现e1a3型BCR-ABL融合基因。患者给予达沙替尼联合VICP方案化疗,首次化疗达完全缓解,后巩固及强化治疗,5个月后复发,出现T315I突变,再诱导未缓解,于发病6月后因感染死亡。结论:少见型e1a3型BCR-ABL融合基因可见于典型Ph染色体阳性ALL患者并产生异常的RQ-PCR扩增条带。结合文献复习,单纯e1a3型Ph染色体阳性ALL治疗反应及预后与其他类型者间未见明显异常,但伴有T315I突变者预后仍较差。

Objective：To analyse the unusual BCR-ABL fusion gene structure of one patient with Ph chromosome positive acute lymphoblastic leukemia（ ALL）.To combine with literature review,we describe its clinical and biological characteristics.Methods：By using bone marrow cell morphology and flow cytometry to determine the type of leukemia and the immunophenotype,conventional chromosome and fluorescence in situ hybridization to determine the cytogenetic abnormalities,real-time fluorescence quantitative PCR（ RQ-PCR） method to determine the specific type of BCR-ABL fusion gene and the copy number.At the same time,we were underway of the Systematic review of the literature.Results：The patient showed the clinical manifestations of ALL,with Ph chromosome positive.However,no amplification curve was detected by using the conventional BCR-ABL kit,further detected with BCR-ABL rare fusion gene kit,found e1 a3 BCR-ABL fusion gene.After dasatinib combined with VICP chemotherapy,the disease was complete remission,then to consolidate and strengthen treatment.After five mounths,the disease was relapse.At this point,T315 I mutation was detected.The disease was remission by the remission induction therapy.Finally,the patient died of infection only 6 months from the onset.Conclusion：The uncommon e1 a3 BCR-ABL fusion gene may occur in patient with Ph chromosome positive ALL and produce unusual RQ-PCR amplification bands.Combined with literature review,the treatment response and prognosis of pure ela3 BCR-ABL ph＋ALL were not significantiy different from other types,but the prognosis of ALL with T315 I mutation was still poor.