Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study of FGFR1 fusions in acute myeloid leukemia

Ting Lei Gu, Valerie L. Goss, Cynthia Reeves, Lana Popova, Julie Nardone, Joan MacNeill, Denise K. Walters, Yi Wang, John Rush, Michael J. Comb, Brian J. Druker, Roberto D. Polakiewicz

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

The 8p11 myeloproliferative syndrome (EMS) is associated with translocations that disrupt the FGFR1 gene. To date, 8 fusion partners of FGFR1 have been identified. However, no primary leukemia cell lines were identified that contain any of these fusions. Here, we screened more than 40 acute myeloid leukemia cell lines for constitutive phosphorylation of STAT5 and applied an immunoaffinity profiling strategy to identify tyrosine-phosphorylated proteins in the KG-1 cell line. Mass spectrometry analysis of KG-1 cells revealed aberrant tyrosine phosphorylation of FGFR1. Subsequent analysis led to the identification of a fusion of the FGFR1OP2 gene to the FGFR1 gene. Small interfering RNA (siRNA) against FGFR1 specifically inhibited the growth and induced apoptosis of KG-1 cells. Thus, the KG-1 cell line provides an in vitro model for the study of FGFR1 fusions associated with leukemia and for the analysis of small molecule inhibitors against FGFR1 fusions.

Original languageEnglish (US)
Pages (from-to)4202-4204
Number of pages3
JournalBlood
Volume108
Issue number13
DOIs
StatePublished - Dec 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Gu, T. L., Goss, V. L., Reeves, C., Popova, L., Nardone, J., MacNeill, J., Walters, D. K., Wang, Y., Rush, J., Comb, M. J., Druker, B. J., & Polakiewicz, R. D. (2006). Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study of FGFR1 fusions in acute myeloid leukemia. Blood, 108(13), 4202-4204. https://doi.org/10.1182/blood-2006-06-026666