Roberts Kathryn G
Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, MS342, Memphis, TN, 38105, USA.
Best Pract Res Clin Haematol. 2018 Dec;31(4):351-356. doi: 10.1016/j.beha.2018.09.003. Epub 2018 Sep 20.
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL), or BCR-ABL1-like ALL, is a high-risk subtype of B-cell precursor ALL characterized by a gene expression profile similar to Ph-positive ALL, a high frequency of IKZF1 alterations, and poor outcome. The prevalence of Ph-like ALL is common among all ages, ranging from 10% to 15% in children to over 25% in young adults. Patients with Ph-like ALL harbor a diverse range of genetic alterations that activate cytokine receptor and kinase signaling and can be targeted with tyrosine kinase inhibitors. The majority of Ph-like ALL alterations are divided into two main groups based on activation of ABL-class or JAK-STAT alterations. Accordingly, preclinical studies and anecdotal reports suggest patients harboring ABL-class fusions are candidates for ABL1-inhibitors, whilst alterations activating the JAK-STAT pathway may be amenable to treatment with JAK inhibitors. Diagnostic screening approaches and precision medicine trials are now being developed and implemented to test the efficacy of targeted therapy with a backbone of chemotherapy, similar to the treatment of Ph-positive ALL.
费城染色体样急性淋巴细胞白血病（Ph样ALL），即BCR-ABL1样ALL，是B细胞前体ALL的一种高危亚型，其特征是基因表达谱与Ph阳性ALL相似、IKZF1改变频率高且预后不良。Ph样ALL在各年龄段均较为常见，在儿童中占10%至15%，在年轻成人中超过25%。Ph样ALL患者存在多种激活细胞因子受体和激酶信号传导的基因改变，可使用酪氨酸激酶抑制剂进行靶向治疗。根据ABL类或JAK-STAT改变的激活情况，大多数Ph样ALL改变可分为两个主要组。因此，临床前研究和轶事报告表明，携带ABL类融合的患者是ABL1抑制剂的候选对象，而激活JAK-STAT途径的改变可能适合用JAK抑制剂治疗。目前正在开发和实施诊断筛查方法及精准医学试验，以测试在化疗基础上进行靶向治疗的疗效，这与Ph阳性ALL的治疗类似。
