Harnessing the power of sphingolipids: Prospects for acute myeloid leukemia.
Bcl-2
Ceramide
Mcl-1
Sphingolipid dysregulation
Sphingosine-1-phosphate
Therapeutics
Journal
Blood reviews
ISSN: 1532-1681
Titre abrégé: Blood Rev
Pays: England
ID NLM: 8708558
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
01
02
2022
revised:
31
03
2022
accepted:
04
04
2022
pubmed:
30
4
2022
medline:
19
8
2022
entrez:
29
4
2022
Statut:
ppublish
Résumé
Acute myeloid leukemia (AML) is an aggressive, heterogenous malignancy characterized by clonal expansion of bone marrow-derived myeloid progenitor cells. While our current understanding of the molecular and genomic landscape of AML has evolved dramatically and opened avenues for molecularly targeted therapeutics to improve upon standard intensive induction chemotherapy, curative treatments are elusive, particularly in older patients. Responses to current AML treatments are transient and incomplete, necessitating the development of novel treatment strategies to improve outcomes. To this end, harnessing the power of bioactive sphingolipids to treat cancer shows great promise. Sphingolipids are involved in many hallmarks of cancer of paramount importance in AML. Leukemic blast survival is influenced by cellular levels of ceramide, a bona fide pro-death molecule, and its conversion to signaling molecules such as sphingosine-1-phosphate and glycosphingolipids. Preclinical studies demonstrate the efficacy of therapeutics that target dysregulated sphingolipid metabolism as well as their combinatorial synergy with clinically-relevant therapeutics. Thus, increased understanding of sphingolipid dysregulation may be exploited to improve AML patient care and outcomes. This review summarizes the current knowledge of dysregulated sphingolipid metabolism in AML, evaluates how pro-survival sphingolipids promote AML pathogenesis, and discusses the therapeutic potential of targeting these dysregulated sphingolipid pathways.
Identifiants
pubmed: 35487785
pii: S0268-960X(22)00024-8
doi: 10.1016/j.blre.2022.100950
pmc: PMC9475810
mid: NIHMS1831562
pii:
doi:
Substances chimiques
Ceramides
0
Sphingolipids
0
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
100950Subventions
Organisme : NCI NIH HHS
ID : K00 CA245802
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA171983
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA044579
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180820
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009109
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.
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