Biology and clinical relevance of acute myeloid leukemia stem cells

Andreas Reinisch, Steven M. Chan, Daniel Thomas, Ravindra Majeti

Research output: Contribution to journalReview article

33 Citations (Scopus)

Abstract

Evidence for the cancer stem cell model was first demonstrated in xenotransplanted blood and bone marrow samples from patients with acute myeloid leukemia (AML) almost two decades ago, supporting the concept that a rare clonal and mutated leukemic stem cell (LSC) population is sufficient to drive leukemic growth. The inability to eliminate LSCs with conventional therapies is thought to be the primary cause of disease relapse in AML patients, and as such, novel therapies with the ability to target this population are required to improve patient outcomes. An important step towards this goal is the identification of common immunophenotypic surface markers and biological properties that distinguish LSCs from normal hematopoietic stem and progenitor cells (HSPCs) across AML patients. This work has resulted in the development of a large number of potential LSC-selective therapies that target cell surface molecules, intracellular signaling pathways, and the bone marrow microenvironment. Here, we will review the basic biology, immunophenotypic detection, and clinical relevance of LSCs, as well as emerging biological and small-molecule strategies that either directly target LSCs or indirectly target these cells through modulation of their microenvironment.

LanguageEnglish
Pages150-164
Number of pages15
JournalSeminars in Hematology
Volume52
Issue number3
DOIs
Publication statusPublished - 1 Jul 2015

ASJC Scopus subject areas

  • Hematology

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