• Cold Spring Harb Perspect Med · Jan 2020

    Review

    Targeting Immunophenotypic Markers on Leukemic Stem Cells: How Lessons from Current Approaches and Advances in the Leukemia Stem Cell (LSC) Model Can Inform Better Strategies for Treating Acute Myeloid Leukemia (AML).

    • Kelly Mitchell and Ulrich Steidl.
    • Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
    • Cold Spring Harb Perspect Med. 2020 Jan 2; 10 (1).

    AbstractTherapies targeting cell-surface antigens in acute myeloid leukemia (AML) have been tested over the past 20 years with limited improvement in overall survival. Recent advances in the understanding of AML pathogenesis support therapeutic targeting of leukemia stem cells as the most promising avenue toward a cure. In this review, we provide an overview of the evolving leukemia stem cell (LSC) model, including evidence of the cell of origin, cellular and molecular disease architecture, and source of relapse in AML. In addition, we explore limitations of current targeted strategies utilized in AML and describe the various immunophenotypic antigens that have been proposed as LSC-directed therapeutic targets. We draw lessons from current approaches as well as from the (pre)-LSC model to suggest criteria that immunophenotypic targets should meet for more specific and effective elimination of disease-initiating clones, highlighting in detail a few targets that we suggest fit these criteria most completely.Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.

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