Interleukin-3 (IL-3) is required for the proliferation, survival and d
ifferentiation of myeloid progenitors. In the absence of IL-3, murine
myeloid 32D.3 cells accumulate in the G1 phase of the cell cycle and s
ubsequently undergo programmed cell, death, or apoptosis. Here we demo
nstrate that enforced expression of the v-raf oncogene suppresses apop
tosis of myeloid 32D.3 cells following the withdrawal of IL-3. Surpris
ingly, steady state levels of Bcl-2, an oncogene known to suppress apo
ptosis, were not dependent upon IL-3 in 32D.3 cells and its levels wer
e not augmented in v-raf clones. This suggests that ability of v-raf t
o suppress apoptosis in the absence of ligand is either Bcl-2 independ
ent or that v-raf kinase promotes Bcl-2 function. v-raf also promoted
growth of these cells in the presence of IL-3. v-raf clones proliferat
ed at an increased rate due to a shortened G1 phase and had decreased
requirements for IL-3 for growth. Therefore, transformation of myeloid
cells by v-raf involves signaling pathways which promote both cell cy
cle progression and cell survival.