V-myc in a simple, single gene retroviral vector causes rapid induction of leukemia and concomitant apoptosis following bone marrow transplantation

Dolnikov, A; Shounan, Y; Millington, M; Mackenzie, K; Symonds, G
April 1998
Leukemia (08876924);Apr98, Vol. 12 Issue 4, p542
Academic Journal
We have previously developed an in vivo model of leukemogen-esis utilizing mice reconstituted with genetically modified bone marrow cells. Based on those studies, a new single gene retro-viral vector has been engineered which efficiently transfers v-myc into immature murine bone marrow cells. All reconstituted mice developed leukemia with a short latency period (5-11 weeks). In addition to hyperproliferation associated with elevated levels of PCNA, extensive apoptosis was also observed in all leukemic animals with p53 accumulating in the apoptotic cells. Whereas bax encoded protein, an effector of p53 apop-totic activity was detected in apoptotic cells, p21[SUPWaf1] protein, a potential mediator of p53 growth suppression was not detected in these cells suggesting that v-myc-induced apoptosis was independent of the ability of p53 to induce p21[SUPWaf1]. These results indicate that apoptosis, a part of the cellular response to v-myc expression, does not prevent leukemia development and that hyperproliferation rather than abrogation of oncogene-induced apoptosis appears to be a critical event in v-myc-induced leukemia.


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