Leukemia stem cells (LSCs) represent a biologically distinct subpopulation of myeloid leukemias, with reduced cell cycle activity and increased resistance to therapeutic challenge. Elucidating the genetic events that mediate leukemia transformation is critical to identifying the mechanisms regulating LSC growth and survival. NYSTEM funded investigator, Craig T. Jordan, Ph.D., and colleagues from the University of Rochester Medical Center used a mouse model of acute leukemia and human leukemia specimens to identify genes cooperatively regulated by the oncogenes BCR-ABL and NU98-HOXA9. These tumor-promoting genes are termed “cooperation response genes (CRG)” and control in vivo growth of primitive leukemia. Dr. Jordan then employed the CRG profile to identify pharmacological compounds that were selectively toxic to both mouse and human leukemia cells. Taken together, these data identify a novel set of genes, previously not described in leukemia, that control leukemia pathogenesis. The CRG-based analyses provide a powerful means to characterize the basic biology of LSCs as well as to identify improved methods for therapeutic targeting to treat leukemia. This work was supported by NYSTEM award C024964.
Ashton JM, Balys M, Neering SJ, Hassane DC, Cowley G, Root DE, Miller PG, Ebert BL, McMurray HR, Land H, Jordan CT. Gene Sets Identified with Oncogene Cooperativity Analysis Regulate In Vivo Growth and Survival of Leukemia Stem Cells. Cell Stem Cell 11: 1-14; 2012 Sep 7.