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Abstract:
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 used 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–RARa–positive cells and suppression of normal hematopoiesis.
All-trans retinoic acid (ATRA) neutralizes the differentiation block and decreases the proliferation rate of
leukemic stem cells in vivo. Prolonged ATRA treatment after chemotherapy can cure patients with APL 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.
