Dynamics of leukemia stem-like cell extinction in acute promyelocytic leukemia

Benjamin Werner, Robert E. Gallagher, Elisabeth M. Paietta, Mark R. Litzow, Martin S. Tallman, Peter H. Wiernik, James L. Slack, Cheryl L. Willman, Zhuoxin Sun, Arne Traulsen, David Dingli

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14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5386-5396
Number of pages11
JournalCancer Research
Volume74
Issue number19
DOIs
StatePublished - Oct 1 2014

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Werner, B., Gallagher, R. E., Paietta, E. M., Litzow, M. R., Tallman, M. S., Wiernik, P. H., Slack, J. L., Willman, C. L., Sun, Z., Traulsen, A., & Dingli, D. (2014). Dynamics of leukemia stem-like cell extinction in acute promyelocytic leukemia. Cancer Research, 74(19), 5386-5396. https://doi.org/10.1158/0008-5472.CAN-14-1210