Guibal, F. C.Alberich-Jorda, M.Hirai, H.Ebralidze, AlexanderLevantini, ElenaDi Ruscio, A.Zhang, PuSantana-Lemos, B. A.Neuberg, DonnaWagers, AmyRego, E. M.Tenen, Daniel2017-07-072009Guibal, F. C., M. Alberich-Jorda, H. Hirai, A. Ebralidze, E. Levantini, A. Di Ruscio, P. Zhang, et al. 2009. “Identification of a Myeloid Committed Progenitor as the Cancer-Initiating Cell in Acute Promyelocytic Leukemia.” Blood 114 (27) (October 1): 5415–5425. doi:10.1182/blood-2008-10-182071.0006-4971http://nrs.harvard.edu/urn-3:HUL.InstRepos:33168735Acute promyelocytic leukemia (APL) is characterized by a block in differentiation and accumulation of promyelocytes in the bone marrow and blood. The majority of APL patients harbor the t(15:17) translocation leading to expression of the fusion protein promyelocytic-retinoic acid receptor . Treatment with retinoic acid leads to degradation of promyelocyticretinoic acid receptor protein and disappearance of leukemic cells; however, 30% of APL patients relapse after treatment. One potential mechanism for relapse is the persistence of cancer “stem” cells in hematopoietic organs after treatment. Using a novel sorting strategy we developed to isolate murine myeloid cells at distinct stages of differentiation, we identified a population of committed myeloid cells (CD34, c-kit, FcRIII/II, Gr1int) that accumulates in the spleen and bone marrow in a murine model of APL. We observed that these cells are capable of efficiently generating leukemia in recipient mice, demonstrating that this population represents the APL cancer–initiating cell. These cells down-regulate the transcription factor CCAAT/enhancer binding protein (C/EBP) possibly through a methylationdependent mechanism, indicating that C/EBP deregulation contributes to transformation of APL cancer–initiating cells. Our findings provide further understanding of the biology of APL by demonstrating that a committed transformed progenitor can initiate and propagate the disease.en-USJournal Article10.1182/blood-2008-10-182071