Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), also referred to as BCR-ABL1–like ALL, is a high-risk subset with a gene expression profile that shares significant overlap with that of Ph-positive (Ph⁺) ALL and is suggestive of activated kinase signaling. Although Ph⁺ ALL is defined by BCR-ABL1 fusion, Ph-like ALL cases contain a variety of genomic alterations that activate kinase and cytokine receptor signaling. These alterations can be grouped into major subclasses that include ABL-class fusions involving ABL1, ABL2, CSF1R, and PDGFRB that phenocopy BCR-ABL1 and alterations of CRLF2, JAK2, and EPOR that activate JAK/STAT signaling. Additional genomic alterations in Ph-like ALL activate other kinases, including BLNK, DGKH, FGFR1, IL2RB, LYN, NTRK3, PDGFRA, PTK2B, TYK2, and the RAS signaling pathway. Recent studies have helped to define the genomic landscape of Ph-like ALL and how it varies across the age spectrum, associated clinical features and outcomes, and genetic risk factors. Preclinical studies and anecdotal reports show that targeted inhibitors of relevant signaling pathways are active in specific Ph-like ALL subsets, and precision medicine trials have been initiated for this high-risk ALL subset.

类似于费城染色体（Ph）的急性淋巴细胞白血病（ALL），也称为BCR - ABL1 –类似于ALL，是一种高风险子集，其基因表达谱与Ph阳性（Ph ⁺）有明显的重叠ALL，提示活化的激酶信号。尽管Ph ⁺ ALL由BCR - ABL1定义融合，类似Ph的ALL病例包含多种基因组改变，可激活激酶和细胞因子受体信号转导。这些改变可以归类为主要的子类，包括涉及表型BCR-ABL1的涉及ABL1，ABL2，CSF1R和PDGFRB的ABL类融合以及激活JAK / STAT信号转导的CRLF2，JAK2和EPOR的改变。Ph样ALL中的其他基因组改变会激活其他激酶，包括BLNK，DGKH，FGFR1，IL2RB，LYN，NTRK3，PDGFRA，PTK2B，TYK2和RAS信号通路。最近的研究帮助确定了Ph样ALL的基因组格局，以及它在年龄谱，相关的临床特征和结局以及遗传危险因素中如何变化。临床前研究和传闻表明，相关信号通路的靶向抑制剂在特定的Ph样ALL子集中具有活性，