TY - JOUR
T1 - Targeting immunophenotypic markers on leukemic stem cells
T2 - How lessons from current approaches and advances in the Leukemia stem cell (LSC) model can inform better strategies for treating acute myeloid leukemia (AML)
AU - Mitchell, Kelly
AU - Steidl, Ulrich
N1 - Publisher Copyright:
© 2020 Cold Spring Harbor Laboratory Press; all rights reserved.
PY - 2020/1
Y1 - 2020/1
N2 - Therapies 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.
AB - Therapies 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.
UR - http://www.scopus.com/inward/record.url?scp=85076701540&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076701540&partnerID=8YFLogxK
U2 - 10.1101/cshperspect.a036251
DO - 10.1101/cshperspect.a036251
M3 - Article
C2 - 31451539
AN - SCOPUS:85076701540
SN - 2157-1422
VL - 10
JO - Cold Spring Harbor Perspectives in Medicine
JF - Cold Spring Harbor Perspectives in Medicine
IS - 1
M1 - a036251
ER -