Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F18%3A00106954" target="_blank" >RIV/00216224:14740/18:00106954 - isvavai.cz</a>
Alternative codes found
RIV/65269705:_____/18:00068820
Result on the web
<a href="http://dx.doi.org/10.1038/s41375-018-0211-0" target="_blank" >http://dx.doi.org/10.1038/s41375-018-0211-0</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41375-018-0211-0" target="_blank" >10.1038/s41375-018-0211-0</a>
Alternative languages
Result language
angličtina
Original language name
Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels
Original language description
The use of the anti-CD20 antibody rituximab has improved the outcome of patients with chronic lymphocytic leukemia (CLL). Rituximab was shown to act via various mechanisms, such as antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), direct apoptosis, or sensitization to chemotherapy (reviewed in ref. [1]). However, the biological function of CD20 and the reasons for the impressive activity of rituximab and other anti-CD20 antibodies remain elusive. It has been suggested, but remains controversial, whether CD20 functions as a calcium channel, couples with CD40 and MHCII, or B-cell receptor (BCR), and whether it has a role in T cell-dependent and -independent immunity [1,2,3,4]. This is also of great clinical interest for the design of combinatorial treatment of rituximab with BCR inhibitors, DNA damaging or immunomodulatory drugs, or CAR T cells. We have previously shown that microenvironmental interactions upregulate the CD20 levels on CLL cells through the CXCR4/SDF-1 axis [5]. Here we describe that higher CD20 expression has a direct role in the BCR signaling in CLL cells, and a BCR-proficient intra-clonal CLL cell subpopulation is more efficiently eliminated by rituximab in vivo due to higher CD20 levels.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
<a href="/en/project/NV16-29622A" target="_blank" >NV16-29622A: THE IMPACT OF THERAPEUTIC TARGETING OF BCR SIGNALLING ON GENE EXPRESSION IN B CELL MALIGNANCIES AND ITS PROGNOSTIC AND PREDICTIVE SIGNIFICANCE</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Leukemia
ISSN
0887-6924
e-ISSN
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Volume of the periodical
32
Issue of the periodical within the volume
9
Country of publishing house
GB - UNITED KINGDOM
Number of pages
4
Pages from-to
2028-2031
UT code for WoS article
000443822800016
EID of the result in the Scopus database
2-s2.0-85050292013