A 62-KILODALTON TYROSINE PHOSPHOPROTEIN CONSTITUTIVELY PRESENT IN PRIMARY CHRONIC PHASE CHRONIC MYELOGENOUS LEUKEMIA ENRICHED LINEAGE NEGATIVE BLAST POPULATIONS

Ph+ chronic myelogenous leukemia (CML) is associated with the reciproc al translocation between chromosomes 9 and 22 culminating in the produ ction of the chimeric p210(bcr/abl) protein possessing elevated protei n tyrosine kinase activity relative to the normal c-abl tyrosine kinas e. Our recent studies have revealed subtle differences in the growth, phenotypic and morphologic characteristics of subpopulations of primar y lin- Ph+ chronic phase CML blasts and comparable primary normal blas ts. In an attempt to correlate these biologic abnormalities and the pr esence of the p210(bcr/abl) protein, we initiated studies to identify differences in proteins constitutively phosphorylated on tyrosine in w hole cell lysates of comparable primary early blast subpopulations der ived from normal and Ph+ chronic phase CML marrows. Immunoblotting wit h anti-P-tyr Abs demonstrated a prominent 62 kDa phosphotyrosyl protei n (pp62) constitutively present in 11/11 Ph+ chronic phase lin-blasts while being virtually undetectable in equivalent amounts of protein de rived from 15/15 and 2/2 comparable normal and Ph-negative chronic pha se blast populations, respectively. Immunoblotting with an Ab reported ly specific for the ras GTPase activating protein (GAP) associated p62 protein revealed that the pp62 present in CML blasts is not immunolog ically related to the former protein. Although the identity of the pp6 2 is presently not known, its prominent presence in chronic phase CML blasts, in which the only known molecular abnormality is putatively th e p210(bcr/abl) protein, strongly suggests that it may be a critical p 210(bcr/abl) substrate involved in an early stage of expansion of the Ph+ clone.