A. Dolnikov et al., V-MYC IN A SIMPLE, SINGLE-GENE RETROVIRAL VECTOR CAUSES RAPID INDUCTION OF LEUKEMIA AND CONCOMITANT APOPTOSIS FOLLOWING BONE-MARROW TRANSPLANTATION, Leukemia, 12(4), 1998, pp. 542-553
We have previously developed an in vivo model of leukemogenesis utiliz
ing mice reconstituted with genetically modified bone marrow cells. Ba
sed on those studies, a new single gene retroviral vector has been eng
ineered which efficiently transfers v-myc into immature murine bone ma
rrow cells. All reconstituted mice developed leukemia with a short lat
ency period (5-11 weeks). In addition to hyperproliferation associated
with elevated levels of PCNA, extensive apoptosis was also observed i
n all leukemic animals with p53 accumulating in the apoptotic cells. W
hereas bar encoded protein, an effector of p53 apoptotic activity was
detected in apoptotic cells, p21(Waf1) protein, a potential mediator o
f p53 growth suppression was not detected in these cells suggesting th
at v-myc-induced apoptosis was independent of the ability of p53 to in
duce p21(Waf1). These results indicate that apoptosis, a part of the c
ellular response to v-myc expression, does not prevent leukemia develo
pment and that hyperproliferation rather than abrogation of oncogene-i
nduced apoptosis appears to be a critical event in v-myc-induced leuke
mia.