A potential role for HSP90 inhibitors in the treatment of JAK2 mutant-positive diseases as demonstrated using quantitative flow cytometry

Joanne Bareng, Iman Jilani, Mercedes Gorre, Hagop Kantarjian, Francis Giles, Alison Hannah, Maher Albitar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The V617F mutation of the JAK2 tyrosine kinase is found in a majority of patients with myeloproliferative disorders. Flow cytometry assays for quantitation of phosphorylated and total protein for JAK2, STAT5, and heat shock proteins (HSPs) were developed to facilitate the study of the JAK/STAT pathway. A cell line homozygous for V617F (HEL) was treated with inhibitors of JAK2 tyrosine kinase activity and the HSP90 inhibitor 17-AAG. 17-AAG reduced HSP90 levels, but increased HSP70 levels. Phospho-STAT5, total STAT5, and total AKT levels were also reduced by17-AAG treatment. Further, phospho-JAK2, total JAK2, and cell viability were reduced to a greater extent by 17-AAG than by the pan-JAK kinase family inhibitor JKII or the JAK2-specific inhibitor AG490, and these inhibitors failed to synergize with 17-AAG. Flow-cytometry-based assays for JAK/STAT signaling pathway and HSPs are likely to have broad clinical utility for monitoring patients with abnormalities in the JAK2 pathway.

Original languageEnglish (US)
Pages (from-to)2189-2195
Number of pages7
JournalLeukemia and Lymphoma
Volume48
Issue number11
DOIs
StatePublished - Nov 2007

Keywords

  • 17-AAG
  • JAK/STAT pathway
  • Mutant JAK2
  • Myeloproliferative disorders
  • V617F

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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