Acute promyelocytic leukemia (APL) is associated with the accumulation of promyelocyte cells in the bone marrow and blood. A majority of APL patients have a chromosomal translocation leading to the expression of a certain protein (promyelocytic-retinoic acid receptor alpha protein). In most patients, treatment with retinoic acid eliminates this protein and causes the leukemia cells to disappear. However, in some patients that does not work.  The cause of this failure has been hypothesized to be due to the continued existence of cancer “stem” cells. In order to identify the cell population that may be responsible for resistance to retinoic acid treatment, HSCI Principal Faculty Member and Head of the HSCI Blood Diseases Program Dan Tenen and fellow researchers used a new approach to sorting myeloid cells from mice at different stages of differentiation. In a recent paper, they showed they can isolate a particular group of myeloid cells that accumulate in the spleen and bone marrow of a mouse model of APL. Further, they showed that these cells are capable of generating leukemia in mice, suggesting that they are APL cancer-initiating cells. These results shed light on the mechanisms involved in the etiology of APL and also contribute to our understanding of how a committed progenitor cell population can cause the disease.

Guibal FC, Alberich-Jorda M, Hirai H, Ebralidze A, Levantini E, Di Ruscio A, Zhang P, Santana-Lemos BA, Neuberg D, Wagers AJ, Rego EM, Tenen DG. Blood. (2009). Identification of a myeloid committed progenitor as the cancer-initiating cell in acute promyelocytic leukemia. Blood 114, 5415-25.