EphB4-VAV1 signaling pathway is associated with imatinib resistance in chronic myeloid leukemia cells

Blood Cells Mol Dis. 2016 Jul:59:58-62. doi: 10.1016/j.bcmd.2016.04.007. Epub 2016 Apr 19.

Abstract

Imatinib (IM) resistant Chronic Myeloid Leukemia (CML) is an important issue to be addressed while treating CML patients. The present study analyzes the role of EphB4-VAV1 signaling in IM-resistant CML. EphB4 and VAV1 were overexpressed in IM-resistant CML patients and K562-R cell line (K562-R). Then, we established stable under-expressing EphB4 cell line K562-R-EphB4-sh. VAV1 was down-regulated in K562-R-EphB4-sh cells. K562-R-EphB4-sh cells gained re-sensitivity to IM and K562-R cells showed mild IM resistance. However, EphB4 was no changed when the VAV1 was down-regulated. EphB4 and VAV1 were overexpressed in IM-resistant CML, VAV1might be the downstream moleculars of EphB4. These results suggest a potential role of EphB4-VAV1 signaling as therapeutic target of IM-resistant CML.

Keywords: Chronic myeloid leukemia; EphB4; Imatinib resistance; VAV1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Resistance, Neoplasm*
  • Humans
  • Imatinib Mesylate / pharmacology*
  • Imatinib Mesylate / therapeutic use
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Proto-Oncogene Proteins c-vav / metabolism*
  • Receptor, EphB4 / metabolism*
  • Signal Transduction

Substances

  • Proto-Oncogene Proteins c-vav
  • VAV1 protein, human
  • Imatinib Mesylate
  • Receptor, EphB4