Abstract
Objective. TEL/PDGFβR is a tyrosine kinase fusion protein associated with the pathogenesis of chronic myelomonocytic leukemia. The following experiments were undertaken to understand the mechanisms whereby TEL/PDGFβR transforms cells. Materials and Methods. Activation of JAK and STAT proteins was studied in an interleukin 3 (IL-3)-dependent cell line, Ba/F3, transformed to IL-3 independence by TEL/PDGFβR. Results. TEL/PDGFβR activates STAT1 and STAT5 in transformed Ba/F3 cells through a JAK- independent pathway. Activation of STAT proteins requires the kinase activity of TEL/PDGFβR. JAK1, JAK2, JAK3, and TYK2 are not phosphorylated by TEL/PDGFβR. However, TEL/PDGFβR can phosphorylate STAT5 in transiently transfected COS cells, suggesting that TEL/PDGFβR may itself be the kinase involved in tyrosine phosphorylation of STAT proteins. In contrast, native PDGFβR stimulated by PDGF ligand does not activate STAT proteins to a significant degree in this hematopoietic context. STAT1 and STAT5 also are activated by TEL/ABL and TEL/JAK2 fusion proteins associated with human leukemia. Conclusions. STAT activation may be a common mechanism of transformation by leukemogenic tyrosine kinase fusion proteins. (C) 2000 International Society for Experimental Hematology.
Original language | English (US) |
---|---|
Pages (from-to) | 584-593 |
Number of pages | 10 |
Journal | Experimental hematology |
Volume | 28 |
Issue number | 5 |
DOIs | |
State | Published - May 2000 |
Keywords
- CMML
- STAT5
- TEL/PDGFβR
- Tyrosine kinases
ASJC Scopus subject areas
- Molecular Biology
- Hematology
- Genetics
- Cell Biology
- Cancer Research