Poster Sessions

CANCER-21

R. Katherine Hyde

R. K. Hyde, Y. Kamikubo, L. Alemu, S. Anderson, M. Kirby, L. Zhao, C. Wang, P. P. Liu

The Leukemia Fusion Gene Cbfb-MYH11 Induce Expression of Two Cytokine Receptors, Il1rl1 and Csf2rb, Which Can Be Used to Identify Leukemia-initiating Cells

Inversion of chromosome 16 (Inv16), which is found in most cases of AML subtype M4Eo, results in fusion of the transcription factor gene CBFB with the MYH11 gene. The resulting fusion gene, CBFB-MYH11 is known to be causative, but not sufficient for leukemia. However, the mechanism by which CBFB-MYH11 initiates leukemogenesis is not well understood. Expression of Cbfb-MYH11 blocks differentiation of embryonic blood cells, characterized by continued expression of Il1rl1 and Csf2rb. To test the effects of Cbfb-MYH11 during adult hematopoiesis, we used an inducible allele of Cbfb-MYH11. 5 days after induction, an abnormal population of Il1rl1+ cells was seen in the immature, lineage minus (lin-) cells of the bone marrow. By 10 days, a population of Il1rl1+, Csf2rb+ cells was seen. This abnormal cell population was transient. In mice that developed leukemia, we saw a second wave of Il1rl1+, Csf2rb+ cells, which expanded until the disease was lethal. To test whether the Csf2rb+ population contained the leukemia initiating cells, we sorted lin- cells for Csf2rb expression and transplanted equal numbers of Cbs2rb- and Csf2rb+ cells into recipient mice. Among the mice that received the Csf2rb- cells, 8 of 9 developed AML. Among the mice transplanted with Csf2rb+ cells, only 1 of 8 mice developed the disease, indicating that the lin-, Csf2rb- cell population is enriched for leukemia initiating cells.