TET-dioxygenase deficiency in oncogenesis and its targeting for tumor-selective therapeutics.
Ascorbic Acid
IDH1/2
MDS
TET-dioxygenases
Therapeutic targeting
Journal
Seminars in hematology
ISSN: 1532-8686
Titre abrégé: Semin Hematol
Pays: United States
ID NLM: 0404514
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
12
10
2020
revised:
04
12
2020
accepted:
19
12
2020
entrez:
29
1
2021
pubmed:
30
1
2021
medline:
6
4
2022
Statut:
ppublish
Résumé
TET2 is one of the most frequently mutated genes in myeloid neoplasms. TET2 loss-of-function perturbs myeloid differentiation and causes clonal expansion. Despite extensive knowledge regarding biochemical mechanisms underlying distorted myeloid differentiation, targeted therapies are lagging. Here we review known biochemical mechanisms and candidate therapies that emerge from this. Specifically, we discuss the potential utility of vitamin C to compensate for TET-dioxygenase deficiency, to thereby restore the biochemical function. An alternative approach exploits the TET-deficient state for synthetic lethality, exploiting the fact that a minimum level of TET-dioxygenase activity is required for cell survival, rendering TET2-mutant malignant cells selectively vulnerable to inhibitors of TET-function.
Identifiants
pubmed: 33509440
pii: S0037-1963(20)30075-5
doi: 10.1053/j.seminhematol.2020.12.002
pmc: PMC7938524
mid: NIHMS1664425
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
Proto-Oncogene Proteins
0
Dioxygenases
EC 1.13.11.-
TET2 protein, human
EC 1.13.11.-
Ascorbic Acid
PQ6CK8PD0R
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
Pagination
27-34Subventions
Organisme : NCRR NIH HHS
ID : C06 RR028655
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA257544
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135795
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest Authors have no conflict of interests.
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