Failure of CDKN2A/B (INK4A/B-ARF)-mediated tumor suppression and resistance to targeted therapy in acute lymphoblastic leukemia induced by BCR-ABL

Genes Dev. 2008 Jun 1;22(11):1411-5. doi: 10.1101/gad.1673908.

Abstract

Deletions of the CDKN2A/B tumor suppressor locus and of the IKAROS and PAX5 genes that promote B-lineage development occur frequently in lymphoid, but not myeloid leukemias initiated by the BCR-ABL tyrosine kinase. Why is this the case, and how do these genetic lesions contribute to an aggressive disease that fails to durably respond to targeted kinase inhibitors?

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Lineage
  • Drug Delivery Systems
  • Drug Resistance, Neoplasm / genetics*
  • Fusion Proteins, bcr-abl
  • Gene Deletion
  • Genes, p16*
  • Humans
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / genetics*

Substances

  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl