Casein Kinase 2 (CK2): A Possible Therapeutic Target in Acute Myeloid Leukemia.
CK2
acute myeloid leukemia
apoptosis
chemoresistance
chemotherapy
cytokine
prognosis
proliferation
silmitasertib
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
21 Jul 2023
21 Jul 2023
Historique:
received:
24
06
2023
revised:
14
07
2023
accepted:
20
07
2023
medline:
29
7
2023
pubmed:
29
7
2023
entrez:
29
7
2023
Statut:
epublish
Résumé
The protein kinase CK2 (also known as casein kinase 2) is one of the main contributors to the human phosphoproteome. It is regarded as a possible therapeutic strategy in several malignant diseases, including acute myeloid leukemia (AML), which is an aggressive bone marrow malignancy. CK2 is an important regulator of intracellular signaling in AML cells, especially PI3K-Akt, Jak-Stat, NFκB, Wnt, and DNA repair signaling. High CK2 levels in AML cells at the first time of diagnosis are associated with decreased survival (i.e., increased risk of chemoresistant leukemia relapse) for patients receiving intensive and potentially curative antileukemic therapy. However, it is not known whether these high CK2 levels can be used as an independent prognostic biomarker because this has not been investigated in multivariate analyses. Several CK2 inhibitors have been developed, but CX-4945/silmitasertib is best characterized. This drug has antiproliferative and proapoptotic effects in primary human AML cells. The preliminary results from studies of silmitasertib in the treatment of other malignancies suggest that gastrointestinal and bone marrow toxicities are relatively common. However, clinical AML studies are not available. Taken together, the available experimental and clinical evidence suggests that the possible use of CK2 inhibition in the treatment of AML should be further investigated.
Identifiants
pubmed: 37509370
pii: cancers15143711
doi: 10.3390/cancers15143711
pmc: PMC10378128
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : Wellcome Trust
ID : 100933
Pays : United Kingdom
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