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Dynamics of leukemia stem-like cell extinction in acute promyelocytic leukemia #MMPMID25082816
Werner B; Gallagher RE; Paietta EM; Litzow MR; Tallman MS; Wiernik PH; Slack JL; Willman CL; Sun Z; Traulsen A; Dingli D
Cancer Res 2014[Oct]; 74 (19): 5386-96 PMID25082816show ga
Many tumors are believed to be maintained by a small number of cancer stem-like cells where cure is thought to require eradication of this cell population. In this study, we investigated the dynamics of acute promyelocytic leukemia (APL) before and during therapy with regard to disease initiation, progression and therapeutic response. This investigation employed a mathematical model of hematopoiesis and a dataset derived from the North American Intergroup Study INT0129. The known phenotypic constraints of APL could be explained by a combination of differentiation blockade of PML-RAR? positive cells and suppression of normal hematopoiesis. ATRA neutralizes the differentiation block and decreases the proliferation rate of leukemic stem cells in vivo. Prolonged ATRA treatment after chemotherapy can cure APL patients by eliminating the stem-like cell population over the course of approximately one year. To our knowledge, this study offers the first estimate of the average duration of therapy that is required to eliminate stem-like cancer cells from a human tumor, with the potential for the refinement of treatment strategies to better manage human malignancy.