Targeting Leukemia-Initiating Cells in Acute Lymphoblastic Leukemia.
Animals
B-Lymphocytes
/ cytology
Disease Models, Animal
Disease Progression
Epigenesis, Genetic
Gene Expression Regulation, Leukemic
Homeostasis
Humans
Immunophenotyping
Leukemia
/ metabolism
Mice
Neoplastic Stem Cells
/ cytology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ metabolism
Remission Induction
Signal Transduction
Stochastic Processes
T-Lymphocytes
/ metabolism
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 08 2021
15 08 2021
Historique:
received:
31
07
2020
revised:
02
12
2020
accepted:
04
01
2021
pubmed:
9
1
2021
medline:
8
1
2022
entrez:
8
1
2021
Statut:
ppublish
Résumé
The concept that different leukemias are developmentally distinct and, like in normal hematopoiesis, generated by restricted populations of cells named leukemia-initiating cells (LIC), is becoming more established. These cancer stem-like cells have been assumed to have unique properties, including the capability of self-renewing and giving rise to "differentiated" or non-LICs that make up the whole tumor. Cell populations enriched with LIC activity have been characterized in different hematopoietic malignancies, including human acute lymphoblastic leukemia (ALL). Related studies have also demonstrated that LICs are functionally distinct from bulk cells and modulated by distinct molecular signaling pathways and epigenetic mechanisms. Here we review several biological and clinical aspects related to LICs in ALL, including (i) immunophenotypic characterization of LIC-enriched subsets in human and mouse models of ALL, (ii) emerging therapeutics against regulatory signaling pathways involved in LIC progression and maintenance in T- and B-cell leukemias, (iii) novel epigenetic and age-related mechanisms of LIC propagation, and (iv) ongoing efforts in immunotherapy to eradicate LIC-enriched cell subsets in relapsed and refractory ALL cases. Current conventional treatments do not efficiently eliminate LICs. Therefore, innovative therapeutics that exclusively target LICs hold great promise for developing an effective cure for ALL.
Identifiants
pubmed: 33414170
pii: 0008-5472.CAN-20-2571
doi: 10.1158/0008-5472.CAN-20-2571
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
4165-4173Informations de copyright
©2021 American Association for Cancer Research.
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