Genetic Alterations Activating Kinase and Cytokine Receptor Signaling in High-Risk Acute Lymphoblastic Leukemia Academic Article uri icon


MeSH Major

  • Genetic Predisposition to Disease
  • Mutation
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Protein-Tyrosine Kinases
  • Receptors, Cytokine
  • Signal Transduction


  • Genomic profiling has identified a subtype of high-risk B-progenitor acute lymphoblastic leukemia (B-ALL) with alteration of IKZF1, a gene expression profile similar to BCR-ABL1-positive ALL and poor outcome (Ph-like ALL). The genetic alterations that activate kinase signaling in Ph-like ALL are poorly understood. We performed transcriptome and whole genome sequencing on 15 cases of Ph-like ALL and identified rearrangements involving ABL1, JAK2, PDGFRB, CRLF2, and EPOR, activating mutations of IL7R and FLT3, and deletion of SH2B3, which encodes the JAK2-negative regulator LNK. Importantly, several of these alterations induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy.


publication date

  • August 14, 2012



  • Academic Article



  • eng

PubMed Central ID

  • PMC3422513

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2012.06.005

PubMed ID

  • 22897847

Additional Document Info

start page

  • 153

end page

  • 66


  • 22


  • 2