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

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.

journal_name

Blood

journal_title

Blood

authors

Gu TL,Goss VL,Reeves C,Popova L,Nardone J,Macneill J,Walters DK,Wang Y,Rush J,Comb MJ,Druker BJ,Polakiewicz RD

doi

10.1182/blood-2006-06-026666

subject

Has Abstract

pub_date

2006-12-15 00:00:00

pages

4202-4

issue

13

eissn

0006-4971

issn

1528-0020

pii

blood-2006-06-026666

journal_volume

108

pub_type

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