Philadelphia chromosome-like acute lymphoblastic leukemia

Sarah K. Tasian, Mignon L. Loh and Stephen P. Hunger


Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like 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 Philadelphia chromosome positive (Ph+) ALL and is suggestive of activated kinase signaling. While 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 outcome, and genetic risk factors. Pre-clinical 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.

  • Submitted June 27, 2017.
  • Accepted September 23, 2017.