Saturday, December 6, 2014, 5:30 PM-7:30 PM
West Building, Level 1 (Moscone Center)
Christine Victoria Ichim, PhD1*, Dzana Dervovic, PhD2*, David Koos, PhD1*, Marciano D. Reis, MD3, Alden Chesney, MD, FRCPC4* and Richard A. Wells, MD, DPhil3,5
1Regen BioPharma, San Diego, CA
2University of Toronto, Toronto, ON, Canada
3Sunnybrook Health Sciences Centre, Toronto, ON, Canada
4Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada
5Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, Canada
The leukemia stem cell model suggests that elucidation of the genes that regulate growth ability within the leukemia cell hierarchy will have important clinical relevance. We showed that the expression of NR2F6 (EAR-2), is greater in clonogenic leukemia single cells than in leukemia cells that do not divide, and that this gene is over-expressed in patients with acute myeloid leukemia and myelodysplastic syndrome. In vivo, overexpression of EAR-2 using a retroviral vector in a chimeric mouse model leads to a condition that resembles myelodysplastic syndrome with hypercellular bone marrow, increased blasts, abnormal localization of immature progenitors, morphological dysplasia of the erythroid lineage and a competitive advantage over wild-type cells, that eventually leads to AML in a subset of the mice, or after secondary-transplantation. Interestingly, animals transplanted with bone marrow that over-expresses EAR-2 develop leukemia that is preceded by expansion of the stem cell compartment in the transplanted mice—suggesting that EAR-2 is an important regulator of hematopoietic stem cell differentiation. Here we report that over-expression of EAR-2 also has a profound effect on the differentiation of erythroid progenitor cells both in vitro and in vivo.
