The regulation and function of CD20: an "enigma" of B-cell biology and targeted therapy

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F20%3A00115840" target="_blank" >RIV/00216224:14740/20:00115840 - isvavai.cz</a>

Alternative codes found

RIV/65269705:_____/20:00072781

Result on the web

<a href="http://www.haematologica.org/content/haematol/105/6/1494.full.pdf" target="_blank" >http://www.haematologica.org/content/haematol/105/6/1494.full.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3324/haematol.2019.243543" target="_blank" >10.3324/haematol.2019.243543</a>

Result language

angličtina

Original language name

The regulation and function of CD20: an "enigma" of B-cell biology and targeted therapy

Original language description

The introduction of anti-CD20 monoclonal antibodies such as rituximab, ofatumumab, or obinutuzumab improved the therapy of Bcell malignancies even though the precise physiological role and regulation of CD20 remains unclear. Furthermore, CD20 expression is highly variable between different B-cell malignancies, patients with the same malignancy, and even between intraclonal subpopulations in an individual patient. Several epigenetic (EZH2, HDAC1/2, HDAC1/4, HDAC6, complex Sin3A-HDAC1) and transcription factors ( USF, OCT1/2, PU.1, PiP, ELK1, ETS1, SP1, NF.B, FOXO1, CREM, SMAD2/3) regulating CD20 expression (encoded by MS4A1) have been characterized. CD20 is induced in the context of microenvironmental interactions by CXCR4/SDF1 (CXCL12) chemokine signaling and the molecular function of CD20 has been linked to the signaling propensity of B-cell receptor (BCR). CD20 has also been shown to interact with multiple other surface proteins on B cells (such as CD40, MHCII, CD53, CD81, CD82, and CBP). Current efforts to combine anti-CD20 monoclonal antibodies with BCR signaling inhibitors targeting BTK or PI3K (ibrutinib, acalabrutinib, idelalisib, duvelisib) or BH3-mimetics (venetoclax) lead to the necessity to better understand both the mechanisms of regulation and the biological functions of CD20. This is underscored by the observation that CD20 is decreased in response to the "BCR inhibitor" ibrutinib which largely prevents its successful combination with rituximab. Several small molecules ( such as histone deacetylase inhibitors, DNA methyl-transferase inhibitors, aurora kinase A/B inhibitors, farnesyltransferase inhibitors, FOXO1 inhibitors, and bryostatin-1) are being tested to upregulate cellsurface CD20 levels and increase the efficacy of anti-CD20 monoclonal antibodies. Herein, we review the current understanding of CD20 function, and the mechanisms of its regulation in normal and malignant B cells, highlighting the therapeutic implications.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30205 - Hematology

Project

<a href="/en/project/NU20-03-00292" target="_blank" >NU20-03-00292: PRIORITIZING DRUG COMBINATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA BASED ON ANALYSIS OF CELL ADAPTATION TO IBRUTINIB AND IDELALISIB IN VIVO</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

haematologica

ISSN

0390-6078

e-ISSN

—

Volume of the periodical

105

Issue of the periodical within the volume

6

Country of publishing house

IT - ITALY

Number of pages

13

Pages from-to

1494-1506

UT code for WoS article

000537771300024

EID of the result in the Scopus database

2-s2.0-85085880945