Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study of FGFR1 fusions in acute myeloid leukemia.
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.
Gu
Ting-Lei
TL
Cell Signaling Technology, Inc., 3 Trask Lane, Danvers, MA 01923, USA.
Goss
Valerie L
VL
Reeves
Cynthia
C
Popova
Lana
L
Nardone
Julie
J
Macneill
Joan
J
Walters
Denise K
DK
Wang
Yi
Y
Rush
John
J
Comb
Michael J
MJ
Druker
Brian J
BJ
Polakiewicz
Roberto D
RD
D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis / Q000235:genetics*; D050799:STAT5 Transcription Factor / Q000096:biosynthesis / Q000235:genetics
C117597:CEP43 protein, human; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D050799:STAT5 Transcription Factor; D051496:Receptor, Fibroblast Growth Factor, Type 1