RETROVIRAL TRANSDUCTION OF HEMATOPOIETIC PROGENITOR CELLS WITH MUTANTP53 PROMOTES SURVIVAL AND PROLIFERATION, MODIFIES DIFFERENTIATION POTENTIAL AND INHIBITS APOPTOSIS
Y. Shounan et al., RETROVIRAL TRANSDUCTION OF HEMATOPOIETIC PROGENITOR CELLS WITH MUTANTP53 PROMOTES SURVIVAL AND PROLIFERATION, MODIFIES DIFFERENTIATION POTENTIAL AND INHIBITS APOPTOSIS, Leukemia, 10(10), 1996, pp. 1619-1628
Mutations in the p53 tumor suppressor gene have been shown to be assoc
iated with many human tumors and various leukemias and lymphomas. To e
xamine whether constitutive overexpression of mutant p53 can effect tr
ansformation of normal hematopoietic cells, a mutant p53 gene was intr
oduced into normal murine bone marrow hematopoietic cells by retrovira
l gene transfer. Compared to vector alone-infected cells, hematopoieti
c progenitor cells transduced with mutant p53 showed increased prolife
rative potential, enhanced cloning efficiencies and a modified differe
ntiation pattern in vitro. In addition, mutant p53-transduced hematopo
ietic cells were more resistant to loss of viability and/or induction
of apoptosis when cultured in a low concentration of serum or in the a
bsence of both growth factors and serum. These effects occurred rapidl
y with no apparent contributory secondary events. No permanent cell li
nes or growth factor-independent cell strains were obtained. The resul
ts indicate that introduction of mutant p53 into normal hematopoietic
cells in vitro contributes to transformation, including enhanced proli
ferative potential, modified differentiation and the suppression of ap
optosis in these cells.