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.

Základní údaje

Originální název

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

Autoři

PAVLASOVÁ, Gabriela (203 Česká republika, domácí), Marek BORSKÝ (203 Česká republika, domácí), Veronika ŠANDOVÁ (203 Česká republika, domácí), Jan OPPELT (203 Česká republika, domácí), Kateřina AMRUZ ČERNÁ (203 Česká republika, domácí), Jitka NOVOTNÁ (203 Česká republika, domácí), Václav ŠEDA (203 Česká republika, domácí), Miloslava FOJTOVÁ (203 Česká republika, domácí), Jiří FAJKUS (203 Česká republika, domácí), Yvona BRYCHTOVÁ (203 Česká republika, domácí), Michael DOUBEK (203 Česká republika, domácí), Šárka POSPÍŠILOVÁ (203 Česká republika, domácí), Jiří MAYER (203 Česká republika, domácí) a Marek MRÁZ (203 Česká republika, garant, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 9.944

Kód RIV

RIV/00216224:14740/18:00106954

Organizační jednotka

Středoevropský technologický institut

DOI

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

UT WoS

000443822800016

Klíčová slova anglicky

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

Štítky

14110212, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 6. 2022 11:31, Mgr. Pavla Foltynová, Ph.D.

Anotace

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.

Návaznosti

NV16-29622A, projekt VaV

Název: 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 a Marek MRÁZ. Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels. Leukemia. London: Nature Publishing Group, 2018, roč. 32, č. 9, s. 2028-2031. ISSN 0887-6924. Dostupné z: 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 a 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, roč.~32, č.~9, s.~2028-2031. ISSN~0887-6924. Dostupné z: https://dx.doi.org/10.1038/s41375-018-0211-0.

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