Oncogenic mechanisms and therapeutic targeting of metabolism in leukemia and lymphoma Review

Authors: Stahl, M.; Epstein-Peterson, Z. D.; Intlekofer, A. M.
Review Title: Oncogenic mechanisms and therapeutic targeting of metabolism in leukemia and lymphoma
Abstract: 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 howspecific pathways of leukemia and lymphoma metabolism confer therapeutic vulnerabilities that can be targeted to inhibit growth or promote differentiation. © 2021 Cold Spring Harbor Laboratory Press; all rights reserved.
Journal Title: Cold Spring Harbor Perspectives in Biology
Volume: 11
Issue: 7
ISSN: 1943-0264
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2021-07-01
Start Page: a035477
Language: English
DOI: 10.1101/cshperspect.a035477
PUBMED: 32816875
PROVIDER: scopus
PMCID: PMC8247556
Notes: Article -- Export Date: 1 September 2021 -- Source: Scopus
Citation Impact
MSK Authors
  1. Maximilian Stahl
    32 Stahl