Am. Wilbanks et al., TEL/PDGF beta R fusion protein activates STAT1 and STAT5: A common mechanism for transformation by tyrosine kinase fusion proteins, EXP HEMATOL, 28(5), 2000, pp. 584-593
Objective. TEL/PDGF beta R is a tyrosine kinase fusion protein associated w
ith the pathogenesis of chronic myelomonocytic leukemia, The following expe
riments were undertaken to understand the mechanisms whereby TEL/PDGF beta
R transforms cells.
Materials and Methods. Activation of JAK: and STAT proteins was studied in
an interleukin 3 (IL3)-dependent cell line, Ba/F3, transformed to IL-3 inde
pendence by TEL/PDGF beta R.
Results. TEL/PDGF beta R activates STAT1 and STAT5 in transformed Ba/F3 cel
ls through a JAK-independent pathway. Activation of STAT proteins requires
the kinase activity of TEL/PDGF beta R, JAK1, JAK2, JAK3, and TYK2 are not
phosphorylated by TEL/PDGR beta R. However, TEL/PDGF beta R can phosphoryla
te STAT5 in transiently transfected COS tells, suggesting that TEL/PDGF bet
a R may itself be the kinase involved in tyrosine phosphorylation of STAT p
roteins. In contrast, native PDGF beta R stimulated by PDGF ligand does not
activate STAT proteins to a significant degree in this hematopoietic conte
xt. STAT1 and STAT5 also are activated by TEL/ABL and TEL/JAK2. fusion prot
eins associated with human leukemia,
Conclusions. STAT activation may be a common mechanism of transformation by
leukemogenic tyrosine kinase fusion proteins. (C) 2000 International Socie
ty for Experimental Hematology. Published by Elsevier Science Inc.