Rituximab primarily targets an intra-clonal BCR signaling
proficient CLL subpopulation characterized by high CD20 levels

J 2018

Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels

PAVLASOVÁ, Gabriela, Marek BORSKÝ, Veronika ŠANDOVÁ, Jan OPPELT, Kateřina AMRUZ ČERNÁ et. al.

Basic information

Original name

Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels

Authors

PAVLASOVÁ, Gabriela (203 Czech Republic, belonging to the institution), Marek BORSKÝ (203 Czech Republic, belonging to the institution), Veronika ŠANDOVÁ (203 Czech Republic, belonging to the institution), Jan OPPELT (203 Czech Republic, belonging to the institution), Kateřina AMRUZ ČERNÁ (203 Czech Republic, belonging to the institution), Jitka NOVOTNÁ (203 Czech Republic, belonging to the institution), Václav ŠEDA (203 Czech Republic, belonging to the institution), Miloslava FOJTOVÁ (203 Czech Republic, belonging to the institution), Jiří FAJKUS (203 Czech Republic, belonging to the institution), Yvona BRYCHTOVÁ (203 Czech Republic, belonging to the institution), Michael DOUBEK (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution) and Marek MRÁZ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Leukemia, London, Nature Publishing Group, 2018, 0887-6924

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 9.944

RIV identification code

RIV/00216224:14740/18:00106954

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1038/s41375-018-0211-0

UT WoS

000443822800016

Keywords in English

CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELLS; EXPRESSION; COMPLEMENT

Abstract

V originále

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.

Links

NV16-29622A, research and development project

Name: VLIV TERAPEUTICKÉ INHIBICE BCR SIGNALIZACE NA GENOVOU EXPRESI U B BUNĚČNÝCH MALIGNIT A JEJÍ PROGNOSTICKÝ A PREDIKTIVNÍ VÝZNAM

Citovat

PAVLASOVÁ, Gabriela, Marek BORSKÝ, Veronika ŠANDOVÁ, Jan OPPELT, Kateřina AMRUZ ČERNÁ, Jitka NOVOTNÁ, Václav ŠEDA, Miloslava FOJTOVÁ, Jiří FAJKUS, Yvona BRYCHTOVÁ, Michael DOUBEK, Šárka POSPÍŠILOVÁ, Jiří MAYER and Marek MRÁZ. Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels. Leukemia. London: Nature Publishing Group, 2018, vol. 32, No 9, p. 2028-2031. ISSN 0887-6924. Available from: https://dx.doi.org/10.1038/s41375-018-0211-0.

@article{1477620,
   author = {Pavlasová, Gabriela and Borský, Marek and Šandová, Veronika and Oppelt, Jan and Amruz Černá, Kateřina and Novotná, Jitka and Šeda, Václav and Fojtová, Miloslava and Fajkus, Jiří and Brychtová, Yvona and Doubek, Michael and Pospíšilová, Šárka and Mayer, Jiří and Mráz, Marek},
   article_location = {London},
   article_number = {9},
   doi = {http://dx.doi.org/10.1038/s41375-018-0211-0},
   keywords = {CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELLS; EXPRESSION; COMPLEMENT},
   language = {eng},
   issn = {0887-6924},
   journal = {Leukemia},
   title = {Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels},
   url = {https://www.nature.com/articles/s41375-018-0211-0},
   volume = {32},
   year = {2018}
}

TY  - JOUR
ID  - 1477620
AU  - Pavlasová, Gabriela - Borský, Marek - Šandová, Veronika - Oppelt, Jan - Amruz Černá, Kateřina - Novotná, Jitka - Šeda, Václav - Fojtová, Miloslava - Fajkus, Jiří - Brychtová, Yvona - Doubek, Michael - Pospíšilová, Šárka - Mayer, Jiří - Mráz, Marek
PY  - 2018
TI  - Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels
JF  - Leukemia
VL  - 32
IS  - 9
SP  - 2028-2031
EP  - 2028-2031
PB  - Nature Publishing Group
SN  - 08876924
KW  - CHRONIC LYMPHOCYTIC-LEUKEMIA
KW  - B-CELLS
KW  - EXPRESSION
KW  - COMPLEMENT
UR  - https://www.nature.com/articles/s41375-018-0211-0
N2  - 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.
ER  -

PAVLASOVÁ, Gabriela, Marek BORSKÝ, Veronika ŠANDOVÁ, Jan OPPELT, Kateřina AMRUZ ČERNÁ, Jitka NOVOTNÁ, Václav ŠEDA, Miloslava FOJTOVÁ, Jiří FAJKUS, Yvona BRYCHTOVÁ, Michael DOUBEK, Šárka POSPÍŠILOVÁ, Jiří MAYER and Marek MRÁZ. Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels. \textit{Leukemia}. London: Nature Publishing Group, 2018, vol.~32, No~9, p.~2028-2031. ISSN~0887-6924. Available from: https://dx.doi.org/10.1038/s41375-018-0211-0.

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