Submitted June 2, 2006
Accepted July 31, 2006
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, and Roberto D Polakiewicz*
Cell Signaling Technology, Inc., Danvers, MA, USA
Oregon Health & Science University Cancer Institute
* Corresponding author; email: rpolakiewicz{at}cellsignal.com.
The 8p11 myeloproliferative syndrome (EMS) is associated with translocations that disrupt the FGFR1 gene. To date, eight fusion partners of FGFR1 have been identified. However, no primary leukemia cell lines were identified that contain any of these fusions. Here, we screened over 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. 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.
