RETROVIRAL TRANSDUCTION OF PHILADELPHIA-POSITIVE CHRONIC MYELOID-LEUKEMIA CELLS WITH A HUMAN MUTANT P53 CDNA AND ITS EFFECT ON IN-VITRO PROLIFERATION

Alterations in the tumor suppressor gene p53 are associated with the pathogenesis of blastic transformation of chronic myeloid leukemia (CML), but their exact role, particularly their relationship with the chimeric protein p210(BCR/ABL), is poorly defined. Point mutations in p53 have been found in some cases of blast crisis and CML blastic cell lines, but it is not clear whether complete inactivation of p53 tumor suppresser function, with or without the production of a mutant protein, can by itself trigger the process of blastic transformation. By using retroviral gene transfer, we showed that the introduction of a mutant human p53 cDNA into hematopoietic progenitor cells from patients with CML in chronic phase, which already contain p210(BCR/ABL), could promote their proliferation in vitro, and occasionally even lead to the growth of factor-independent colonies. We conclude that a mutant p53 may act in synergy with p210(BCR)/(ABL) and promote the survival and proliferation of CML hematopoietic stem and progenitor cells in vitro.