Phosphoproteomic analysis of AML cell lines identifies leukemic oncogenes

Denise K. Walters, Valerie L. Goss, Eric P. Stoffregen, Ting Lei Gu, Kimberly Lee, Julie Nardone, Laura McGreevey, Michael C. Heinrich, Michael W. Deininger, Roberto Polakiewicz, Brian J. Druker

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

STAT5 is constitutively phosphorylated in leukemic cells in approximately 70% of acute myeloid leukemia (AML) patients. To identify kinase candidates potentially responsible for STAT5 phosphorylation, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometry to detect phosphoproteins in AML cell lines. We established TEL-ARG and BCR-ABL fusion proteins as the mechanism underlying STAT5 phosphorylation in HT-93 and KBM-3 cells, respectively. In addition, we identified a JAK2 pseudokinase domain mutation in HEL cells and using siRNA downregulation, established JAK2 as the kinase responsible for phosphorylating STAT5. This study illustrates the benefit of LC-MS/MS mass spectrometry and siRNA for the identification of novel targets and mutations.

Original languageEnglish (US)
Pages (from-to)1097-1104
Number of pages8
JournalLeukemia Research
Volume30
Issue number9
DOIs
StatePublished - Sep 1 2006

Keywords

  • AML
  • Leukemia
  • Phosphopeptide
  • Tyrosine kinases

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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  • Cite this

    Walters, D. K., Goss, V. L., Stoffregen, E. P., Gu, T. L., Lee, K., Nardone, J., McGreevey, L., Heinrich, M. C., Deininger, M. W., Polakiewicz, R., & Druker, B. J. (2006). Phosphoproteomic analysis of AML cell lines identifies leukemic oncogenes. Leukemia Research, 30(9), 1097-1104. https://doi.org/10.1016/j.leukres.2006.01.001