TY - JOUR
T1 - Acute myeloid leukemia
T2 - therapeutic targeting of stem cells
AU - Pabon, Cindy M.
AU - Abbas, Hussein A.
AU - Konopleva, Marina
N1 - Funding Information:
Dr. Konopleva has grant funding from (1) IRG CD200 Stem Cell Spec Mech - Overexpression of CD200 is a Stem Cell- Specific Mechanism of Immune Evasion in AML and (2) CCSG - P30 CA016672.
Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - Introduction: Despite advances in the treatment of acute myeloid leukemia (AML), long-term survival remains low. In 1994, it was proposed that leukemic stem cells (LSCs) played a key role in relapsed and refractory disease. LSCs are capable of self-renewal, proliferation, differentiation, immune evasion, and drug resistance through several unique mechanisms. More recent leukemia drug development initiatives have included efforts to target LSCs. With LSCs, the challenge with such drug design is finding a way to selectively target LSCs while sparing normal hematopoietic stem cells (HSCs). Areas covered: In this review, we explore the evolving knowledge of the unique LSC biology and physiology in the scientific literature, while noting the several agents that have been designed throughout the years to target this subgroup of leukemic cells. Our review includes discussion on chimeric antigen receptor T cells, monoclonal antibodies, antibody-drug conjugates against cell surface markers, signaling pathway targets, pro-apoptotic agents, epigenetic regulators, and more. Expert opinion: As our understanding of the intricate pathophysiology of LSCs continues to grow, it is clear that targeting such heterogenous cells successfully will require a thoughtful and multi-modal approach.
AB - Introduction: Despite advances in the treatment of acute myeloid leukemia (AML), long-term survival remains low. In 1994, it was proposed that leukemic stem cells (LSCs) played a key role in relapsed and refractory disease. LSCs are capable of self-renewal, proliferation, differentiation, immune evasion, and drug resistance through several unique mechanisms. More recent leukemia drug development initiatives have included efforts to target LSCs. With LSCs, the challenge with such drug design is finding a way to selectively target LSCs while sparing normal hematopoietic stem cells (HSCs). Areas covered: In this review, we explore the evolving knowledge of the unique LSC biology and physiology in the scientific literature, while noting the several agents that have been designed throughout the years to target this subgroup of leukemic cells. Our review includes discussion on chimeric antigen receptor T cells, monoclonal antibodies, antibody-drug conjugates against cell surface markers, signaling pathway targets, pro-apoptotic agents, epigenetic regulators, and more. Expert opinion: As our understanding of the intricate pathophysiology of LSCs continues to grow, it is clear that targeting such heterogenous cells successfully will require a thoughtful and multi-modal approach.
KW - acute myeloid leukemia
KW - hematopoiesis
KW - Leukemic stem cell
KW - targeted therapy
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U2 - 10.1080/14728222.2022.2083957
DO - 10.1080/14728222.2022.2083957
M3 - Review article
C2 - 35634856
AN - SCOPUS:85131554812
SN - 1472-8222
VL - 26
SP - 547
EP - 556
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
IS - 6
ER -