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 p athogenesis of blastic transformation of chronic myeloid leukemia (CML ), but their exact role, particularly their relationship with the chim eric protein p210(BCR/ABL), is poorly defined. Point mutations in p53 have been found in some cases of blast crisis and CML blastic cell lin es, but it is not clear whether complete inactivation of p53 tumor sup presser 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 promo te their proliferation in vitro, and occasionally even lead to the gro wth of factor-independent colonies. We conclude that a mutant p53 may act in synergy with p210(BCR)/(ABL) and promote the survival and proli feration of CML hematopoietic stem and progenitor cells in vitro.