Targeting Casein Kinase 1 (CK1) in Hematological Cancers

J 2020

Targeting Casein Kinase 1 (CK1) in Hematological Cancers

JANOVSKÁ, Pavlína, Emmanuel NORMANT, Hari MISKIN and Vítězslav BRYJA

Basic information

Original name

Targeting Casein Kinase 1 (CK1) in Hematological Cancers

Authors

JANOVSKÁ, Pavlína (203 Czech Republic, guarantor, belonging to the institution), Emmanuel NORMANT, Hari MISKIN and Vítězslav BRYJA (203 Czech Republic, belonging to the institution)

Edition

International Journal of Molecular Sciences, Basel, MDPI, 2020, 1422-0067

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.923

RIV identification code

RIV/00216224:14310/20:00114621

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.3390/ijms21239026

UT WoS

000597481100001

Keywords in English

casein kinase 1; CK1 alpha CK1 epsilon leukemia; CLL; AML; MM; inhibitors; umbralisib; WNT pathway

Abstract

V originále

The casein kinase 1 enzymes (CK1) form a family of serine/threonine kinases with seven CK1 isoforms identified in humans. The most important substrates of CK1 kinases are proteins that act in the regulatory nodes essential for tumorigenesis of hematological malignancies. Among those, the most important are the functions of CK1s in the regulation of Wnt pathways, cell proliferation, apoptosis and autophagy. In this review we summarize the recent developments in the understanding of biology and therapeutic potential of the inhibition of CK1 isoforms in the pathogenesis of chronic lymphocytic leukemia (CLL), other non-Hodgkin lymphomas (NHL), myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and multiple myeloma (MM). CK1 delta/epsilon inhibitors block CLL development in preclinical models via inhibition of WNT-5A/ROR1-driven non-canonical Wnt pathway. While no selective CK1 inhibitors have reached clinical stage to date, one dual PI3K delta and CK1 epsilon inhibitor, umbralisib, is currently in clinical trials for CLL and NHL patients. In MDS, AML and MM, inhibition of CK1 alpha, acting via activation of p53 pathway, showed promising preclinical activities and the first CK1 alpha inhibitor has now entered the clinical trials.

Links

EF16_025/0007381, research and development project

Name: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

GX19-28347X, research and development project

Name: Molekulární a funkční analýza biologie kasein kinázy 1

Investor: Czech Science Foundation

Citovat

JANOVSKÁ, Pavlína, Emmanuel NORMANT, Hari MISKIN and Vítězslav BRYJA. Targeting Casein Kinase 1 (CK1) in Hematological Cancers. International Journal of Molecular Sciences. Basel: MDPI, 2020, vol. 21, No 23, p. 1-19. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms21239026.

@article{1719498,
   author = {Janovská, Pavlína and Normant, Emmanuel and Miskin, Hari and Bryja, Vítězslav},
   article_location = {Basel},
   article_number = {23},
   doi = {http://dx.doi.org/10.3390/ijms21239026},
   keywords = {casein kinase 1; CK1 alpha CK1 epsilon leukemia; CLL; AML; MM; inhibitors; umbralisib; WNT pathway},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Targeting Casein Kinase 1 (CK1) in Hematological Cancers},
   url = {https://doi.org/10.3390/ijms21239026},
   volume = {21},
   year = {2020}
}

TY  - JOUR
ID  - 1719498
AU  - Janovská, Pavlína - Normant, Emmanuel - Miskin, Hari - Bryja, Vítězslav
PY  - 2020
TI  - Targeting Casein Kinase 1 (CK1) in Hematological Cancers
JF  - International Journal of Molecular Sciences
VL  - 21
IS  - 23
SP  - 1-19
EP  - 1-19
PB  - MDPI
SN  - 14220067
KW  - casein kinase 1
KW  - CK1 alpha CK1 epsilon leukemia
KW  - CLL
KW  - AML
KW  - MM
KW  - inhibitors
KW  - umbralisib
KW  - WNT pathway
UR  - https://doi.org/10.3390/ijms21239026
L2  - https://doi.org/10.3390/ijms21239026
N2  - The casein kinase 1 enzymes (CK1) form a family of serine/threonine kinases with seven CK1 isoforms identified in humans. The most important substrates of CK1 kinases are proteins that act in the regulatory nodes essential for tumorigenesis of hematological malignancies. Among those, the most important are the functions of CK1s in the regulation of Wnt pathways, cell proliferation, apoptosis and autophagy. In this review we summarize the recent developments in the understanding of biology and therapeutic potential of the inhibition of CK1 isoforms in the pathogenesis of chronic lymphocytic leukemia (CLL), other non-Hodgkin lymphomas (NHL), myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and multiple myeloma (MM). CK1 delta/epsilon inhibitors block CLL development in preclinical models via inhibition of WNT-5A/ROR1-driven non-canonical Wnt pathway. While no selective CK1 inhibitors have reached clinical stage to date, one dual PI3K delta and CK1 epsilon inhibitor, umbralisib, is currently in clinical trials for CLL and NHL patients. In MDS, AML and MM, inhibition of CK1 alpha, acting via activation of p53 pathway, showed promising preclinical activities and the first CK1 alpha inhibitor has now entered the clinical trials.
ER  -

JANOVSKÁ, Pavlína, Emmanuel NORMANT, Hari MISKIN and Vítězslav BRYJA. Targeting Casein Kinase 1 (CK1) in Hematological Cancers. \textit{International Journal of Molecular Sciences}. Basel: MDPI, 2020, vol.~21, No~23, p.~1-19. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms21239026.

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