Oncogenic Mechanisms and Therapeutic Targeting of Metabolism in Leukemia and Lymphoma.
Journal
Cold Spring Harbor perspectives in medicine
ISSN: 2157-1422
Titre abrégé: Cold Spring Harb Perspect Med
Pays: United States
ID NLM: 101571139
Informations de publication
Date de publication:
01 07 2021
01 07 2021
Historique:
pubmed:
21
8
2020
medline:
16
12
2021
entrez:
21
8
2020
Statut:
epublish
Résumé
Leukemias and lymphomas acquire the capacity for unrestrained cell growth and proliferation in conjunction with loss of responsiveness to molecular programs that promote terminal differentiation. Malignant cells generate the building blocks required for rapid cell division through both increased acquisition of nutrients from the environment and reprogrammed intermediary metabolism to shunt these molecules into producing the protein, lipids, and nucleic acids that comprise cell biomass. These accelerated metabolic processes require energy in the form of ATP and reducing equivalents in the form of NADPH, which power biosynthetic reactions and buffer oxidative stress encountered by the metabolically active cancer cell. Cancer-associated metabolic alterations can also promote accumulation or depletion of specific metabolites that directly regulate cell fate and function, thereby coupling metabolic reprogramming to dedifferentiation and stemness. This review will focus on the mechanisms by which leukemia and lymphoma cells rewire cellular metabolism to support: (1) bioenergetics, (2) biomass accumulation, (3) redox balance, and (4) differentiation blockade. We will further highlight examples of how specific pathways of leukemia and lymphoma metabolism confer therapeutic vulnerabilities that can be targeted to inhibit growth or promote differentiation.
Identifiants
pubmed: 32816875
pii: cshperspect.a035477
doi: 10.1101/cshperspect.a035477
pmc: PMC8247556
pii:
doi:
Substances chimiques
Carcinogens
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : K08 CA201483
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA251543
Pays : United States
Informations de copyright
Copyright © 2021 Cold Spring Harbor Laboratory Press; all rights reserved.
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