title: Dynamics of leukemia stem-like cell extinction in acute promyelocytic leukemia.
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-RARα-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.
authors.affiliation: Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Werner
authors.affiliation: Montefiore Medical Center, Bronx, New York, New York.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gallagher
authors.affiliation: Montefiore Medical Center, Bronx, New York, New York.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Paietta
authors.affiliation: Division of Hematology and Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
authors.affiliation: Northwestern University, Chicago, Illinois.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.affiliation: Beth Israel Medical Center, New York, New York.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Wiernik
authors.affiliation: Division of Hematology, Mayo Clinic Arizona, Scottsdale, Arizona.
authors.forename: James L
authors.initials: JL
authors.lastname: Slack
authors.affiliation: University of New Mexico Cancer Center, Albuquerque, New Mexico.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Willman
authors.affiliation: Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Zhuoxin
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Traulsen
authors.affiliation: Division of Hematology and Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota. Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota. dingli.david@mayo.edu.
authors.forename: David
authors.initials: D
authors.lastname: Dingli
mesh_terms: D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D013269:Stochastic Processes; D014212:Tretinoin / Q000627:therapeutic use
chemical_list: D014212:Tretinoin
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