费城染色体样急性淋巴细胞白血病的研究进展

Advances in Philadelphia chromosome-like acute lymphoblastic leukemia

费城染色体样急性淋巴细胞白血病(Philadelphia chromosome-like acute lymphoblastic leukemia,BCR-ABL1-like ALL)是2009年新定义的一个ALL亚型,为一组基因表达谱与费城染色体(Ph/BCR-ABL1)阳性ALL高度相似的Ph/BCR-ABL1阴性ALL。然而目前该疾病尚无确切统一的诊断标准。BCR-ABL1-like ALL通常对化学治疗耐药,复发率高,预后较差。其分子生物学特征大多为含有影响细胞因子受体样因子2(cytokine receptor like factor 2,CRLF2)和(或)酪氨酸激酶相关信号通路的基因异常,其中以CRLF2过表达、JAK-STAT通路及ABL族激酶相关基因异常最为多见。这些基因异常可作为相应的治疗靶点,且已有体外和动物实验及临床数据支持靶向治疗的作用。在常规多药化学治疗的基础上,联合靶向治疗、细胞免疫治疗及异基因造血干细胞移植等治疗策略,有望改善BCR-ABL1-like ALL的不良预后。该文从定义、诊断、临床特征、分子生物学特点及治疗5个方面阐述BCR-ABL1-like ALL的研究现状。

Philadelphia chromosome-like acute lymphoblastic leukemia(BCR-ABL1-like ALL)is a newly defined ALL subtype in 2009.It is Philadelphia chromosome(Ph)/BCR-ABL1-negative and characterized by a set of gene expression profile which is highly similar to that of Ph/BCR-ABL1-positive ALL.However,there is no definitive unified diagnostic criteria yet.BCR-ABL1-like ALL is generally resistant to chemotherapy,with a high relapsed rate and poor prognosis.It harbors a diverse range of genetic alterations that affect cytokine receptor and/or signal transduction pathway of tyrosine kinase.Overexpression of CRLF2,JAK-STAT pathway abnormalities and ABL-class gene rearrangements are the most common.These genetic aberrations could be therapeutic targets.Both in vitro and in vivo experiments and clinical data support the efficacy of targeted therapy.Beside conventional multi-drug chemotherapy,the combination of targeted therapy,cellular immunotherapy and allogeneic hematopoietic stem cell transplantation is promising to improve the prognosis of BCR-ABL1-like ALL.In this paper,the research status of BCR-ABL1-like ALL is described from five aspects:definition,diagnosis,clinical characteristics,molecular biological characteristics and treatment.