TYROSINE-PHOSPHORYLATED PROTEINS IN CHRONIC MYELOGENOUS LEUKEMIA

An aberrantly expressed and highly active abl tyrosine kinase (p210bcr-abl) appears critical for the development and pathogenesis of chronic myelogenous-leukemia (CML). CML cells and cell lines each displayed a similar spectrum of phosphotyrosyl proteins. Analysis of these proteins by glycerol-gradient ultracentrifugation showed that many apparently existed as multimeric complexes. Confirming this, several of these proteins co-immunoprecipitated, along with the p210bcr-abl, with antibody to abl. Included were co-precipitating proteins identified as the p120 ras GTPase-activating protein (GAP) and the p62 protein that binds both to GAP and to a number of other tyrosine-phosphorylated proteins having peptide regions homologous to the second domain of src. Because p62, ras GAP and ras are involved in growth-factor and oncogene activation of cells, this pathway may also play an important role in CML.