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

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Publikace nespadá pod Ekonomicko-správní fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.
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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

Rok publikování 2018
Druh Článek v odborném periodiku
Časopis / Zdroj Leukemia
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www https://www.nature.com/articles/s41375-018-0211-0
Doi http://dx.doi.org/10.1038/s41375-018-0211-0
Klíčová slova CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELLS; EXPRESSION; COMPLEMENT
Popis 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.
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