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

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.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0024-3444-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0024-3445-8
Genre: Journal Article

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 Creators:
Werner, Benjamin1, Author              
Gallagher, Robert E., Author
Paietta, Elisabeth M., Author
Litzow, Mark R., Author
Tallman, Martin S., Author
Wiernik, Peter H., Author
Slack, James L., Author
Willman, Cheryl L., Author
Sun, Zhuoxin, Author
Traulsen, Arne1, Author              
Dingli, David, Author
Affiliations:
1Research Group Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445641              

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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.

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Language(s): eng - English
 Dates: 2014-07-172014-04-182014-07-242014-07-312014-10-01
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1158/0008-5472.CAN-14-1210
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Title: Cancer research : an official organ of the American Association for Cancer Research
  Other : Cancer Res.
Source Genre: Journal
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Publ. Info: Baltimore, Md. : Waverly Press
Pages: - Volume / Issue: 74 (19) Sequence Number: - Start / End Page: 5386 - 5396 Identifier: ISSN: 0008-5472 (print)
ISSN: 0099-7013 (print)
ISSN: 0099-7374 (print)
ISSN: 1538-7445 (online)
CoNE: /journals/resource/991042743115962