PMID: 9633897Jun 20, 1998Paper

Differential constitutive activation between STAT-related proteins and MAP kinase in primary acute myelogenous leukaemia

British Journal of Haematology
F HayakawaH Saito

Abstract

Many cytokines and growth factors stimulate multiple signal transduction pathways essential for proliferation in human acute leukaemia cells, including a mitogen-activated protein (MAP) kinase pathway and a Janus kinase (JAK)-STAT (signal transducers and activators of transcription) pathway. We have previously shown constitutive activation of MAP kinase in approximately 50% of acute myelogenous leukaemia (AML) samples. Recently, STAT proteins have been reported to be constitutively activated in 10-20% of AML cases. STAT3 and STAT5 are the main STAT proteins activated in haemopoietic progenitors in response to cytokines such as IL-3, GM-CSF, erythropoietin and thrombopoietin. Although the possibility of STAT1 protein as a substrate for MAP kinase at a serine residue has been suggested, the cross-talk between STATs and MAP kinase pathways in vivo, especially in leukaemia cells, remains unknown. We examined the phosphorylation of STAT 3 and STAT 5 at the tyrosine residues in AML samples in which MAP kinase activity had already been found. 40/50 primary AML cases (80%) exhibited constitutive tyrosine phosphorylation of STAT5. Electrophoretic mobility shift assay showed DNA binding activity of STAT5 correlated with tyrosine phosphor...Continue Reading

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Citations

May 5, 2001·Leukemia Research·R L Ilaria
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