English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

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

MPS-Authors
/persons/resource/persons56995

Werner,  Benjamin
Research Group Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Max Planck Society;

/persons/resource/persons56973

Traulsen,  Arne
Research Group Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Werner, B., Gallagher, R. E., Paietta, E. M., Litzow, M. R., Tallman, M. S., Wiernik, P. H., et al. (2014). Dynamics of leukemia stem-like cell extinction in acute promyelocytic leukemia. Cancer research: an official organ of the American Association for Cancer Research, 74(19), 5386-5396. doi:10.1158/0008-5472.CAN-14-1210.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0024-3444-A
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.