INCREASED DETECTION OF SPECIFIC TYROSINE PHOSPHOPROTEINS CORRELATES WITH TUMOR PROGRESSION OF ABELSON VIRUS-INFECTED LYMPHOCYTES

Leukemias induced with the v-abl or BCR/ABL oncogene undergo a process of tumor progression which suggests that the ABL oncogene is required but not sufficient for full transformation. In order to identify cell ular changes that correlate with progression to full transformation in v-abl transformed lymphoblasts Abelson virus (A-MuLV)-infected murine bone marrow was plated over a pre-established stromal feeder layer. S hortly after A-MuLV infection, transformed lymphoblasts were poorly on cogenic, but over time, progressed in a stepwise manner to a more onco genic state. The transformants first acquired the ability to grow effi ciently in agar, but only over the feeder layer. They next progressed to efficient feeder-independent growth in liquid culture, and then to efficient feeder-independent growth in soft agar. Cell lines that reac hed the advanced stage of feeder-independent agar growth showed increa sed detection by antiphosphotyrosine Western blot of the GAP-associate d p62 phosphoprotein as well as of a 55 kDa phosphoprotein while detec tion of the P160 v-abl phosphoprotein remained constant throughout all stages of progression. Although the identity of the p55 phosphoprotei n and the mechanism by which detection of p55 and p62 phosphoproteins change on the Western blots during tumor progression are unknown, the data demonstrate that these changes strongly correlate with the stage of progression of v-abl-transformed cells and raise the possibility th at these changes may play a role in tumor progression in this model.