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Therapeutic Implications of Leukemic Stem Cell Pathways

Authors' Affiliations: ¹ Department of Medicine, University of Maryland Marlene and Stewart Greenebaum Cancer Center; ² Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; and ³ Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland

Requests for reprints: Angelika M. Burger, Bressler Research Building, Room 9-039, 655 West Baltimore Street, Baltimore, MD 21201. Phone: 410-328-3914; Fax: 410-328-6559; E-mail: aburger{at}som.umaryland.edu.

Abstract

An emerging concept in cancer biology is that a rare population of cancer stem cells exists among the heterogeneous cell mass that constitutes a tumor. This concept is best understood in human myeloid leukemia. Normal and malignant hematopoietic stem cell functions are defined by a common set of critical stemness genes that regulate self-renewal and developmental pathways. Several stemness factors, such as Notch or telomerase, show differential activation in normal hematopoietic versus leukemia stem cells. These differences could be exploited therapeutically even with drugs that are already in clinical use for the treatment of leukemia. The translation of novel and existing leukemic stem cell–directed therapies into clinical practice, however, will require changes in clinical trial design and the inclusion of stem cell biomarkers as correlative end points.