Roberts Kathryn G
Department of Pathology, 262 Danny Thomas Place, St. Jude Children's Research Hospital, Memphis, TN, 38112, USA.
Best Pract Res Clin Haematol. 2017 Sep;30(3):212-221. doi: 10.1016/j.beha.2017.07.003. Epub 2017 Jul 6.
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently described subtype of B-cell precursor ALL with a gene expression profile similar to Ph-positive ALL and a high frequency of IKZF1 alterations. The prevalence of Ph-like ALL increases with age, ranging from 10-15% of children to over 25% of young adults with ALL. It occurs more frequently in males and is associated with adverse clinical features including elevated minimal residual disease levels and poor survival in both children and adults. The genomic landscape of Ph-like ALL is characterized by a diverse range of genetic alterations that dysregulate cytokine receptor and kinase signaling pathways, including rearrangement of CRLF2 and other tyrosine kinases (predominantly ABL-class and Janus kinases). Compelling preclinical data suggest patients harboring ABL-class rearrangements are candidates for ABL1-inhibitors, whilst alterations activating the JAK-STAT pathway may be amenable to treatment with JAK inhibitors. The success of combinatorial treatment of tyrosine kinase inhibitors with chemotherapy in Ph-positive ALL provides a framework for testing this approach in Ph-like ALL. Ongoing prospective studies will determine if incorporation of targeted therapy with intensive chemotherapy regimens will improve the outcome of patients with Ph-like ALL.
费城染色体样急性淋巴细胞白血病（Ph样ALL）是一种最近描述的B细胞前体ALL亚型，其基因表达谱与Ph阳性ALL相似，且IKZF1改变频率较高。Ph样ALL的患病率随年龄增长而增加，在儿童ALL中占10%-15%，在年轻成人ALL中超过25%。它在男性中更常见，与不良临床特征相关，包括儿童和成人的微小残留病水平升高和生存率低。Ph样ALL的基因组格局以多种遗传改变为特征，这些改变会失调细胞因子受体和激酶信号通路，包括CRLF2和其他酪氨酸激酶（主要是ABL类和Janus激酶）的重排。令人信服的临床前数据表明，携带ABL类重排的患者是ABL1抑制剂的候选者，而激活JAK-STAT通路的改变可能适合用JAK抑制剂治疗。酪氨酸激酶抑制剂与化疗联合治疗Ph阳性ALL的成功为在Ph样ALL中测试这种方法提供了框架。正在进行的前瞻性研究将确定在强化化疗方案中加入靶向治疗是否会改善Ph样ALL患者的预后。
