摘要/Abstract
摘要： 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。
关键词: 费城染色体样急性淋巴细胞白血病, 基因表达谱, 酪氨酸激酶抑制剂, 预后, 分子靶向治疗
Abstract:
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.
Key words: Philadelphia chromosome-like acute lymphoblastic leukemia (BCR-ABL1-like ALL), gene expression profiling, tyrosine kinase inhibitor, prognosis, molecular targeted therapy
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