*3.1.8 The Philadelphia Chromosome – like Acute Lymphoblastic Leukemia (Ph-like ALL)*

Ph-like, or BCR-ABL1-like ALL is characterized by a leukemic cell transcriptional profile similar to Ph + ALL but lack the BCR-ABL1 fusion gene [45, 46]. Ph-like ALL is vary heterogeneous in the altered genes and the form (rearrangements, mutations, or deletions) of alterations that result in the activated tyrosine kinase or cytokine receptor signaling characteristic of this subtype of ALL [46]. However, these fall into four main groups: (1) Alterations driving JAK–STAT signaling, most commonly rearrangements of CRLF2 (IGH-CRLF2, P2RY8-CRLF2, CRLF2 F232C), and less commonly, rearrangements of JAK2, EPOR, or TYK2, and mutations/deletions of IL7R, SH2B3, JAK1, JAK3, TYK2, IL2RB); (2) fusions involving ABL-class genes (ABL1, ABL2, CSF1R, LYN, PDGFRA, PDGFRB); (3) mutations activating Ras signaling (NRAS, KRAS, PTPN11); and (4) less common fusions (FLT3, FGFR1, NTRK3) [35, 36, 47]. Ph-like is associated with high-risk clinical characteristics, poor response to induction chemotherapy, elevated levels of minimal residual disease (MRD), and/or poor survival [48].
