WILD-TYPE P53 MODULATES APOPTOSIS OF NORMAL, IL-3 DEPRIVED, HEMATOPOIETIC-CELLS

Apoptotic cell death is an active process which regulates the maintena nce of the hematopoietic homeostasis. It has been reported that wild-t ype p53 (wt-p53) protein induces apoptosis in leukemia cells. To asses s whether p53 is involved in the apoptotic process of normal hematopoi etic cells, we introduced the temperature-sensitive p53Val(135) mutant into the murine myeloid precursor cell line 32Dcl3. These are diploid , non-tumorigenic cells whose survival and proliferation are dependent upon growth factor supply (IL-3 and serum). Overexpression of wt-p53 protein does not affect morphology and proliferation of 32D cells as l ong as they are maintained in the presence of IL-3. However, after IL- 3 withdrawal, wt-p53 overexpression significantly accelerates apoptosi s. This phenomenon is IL-3 specific since no differences in death rate s induced by serum starvation are found between parental cells and p53 -transfectants. When the latter experiments are carried out at 37 degr ees C with p53 protein in mutant conformation, an extended survival of 32D cells is observed after IL-3 deprivation, but not after serum wit hdrawal. Taken together, these results show that wt-p53 actively media tes the apoptosis due to the absence of specific growth factors, such as IL-3, suggesting that p53 might be involved in the response of myel oid precursors to environmental cytokines for the maintenance of the h ematopoietic homeostasis.