Rituximab induces rapid blood repopulation by CLL cells mediated through their release from immune niches and complement exhaustion
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F21%3A00074824" target="_blank" >RIV/65269705:_____/21:00074824 - isvavai.cz</a>
Alternative codes found
RIV/00209805:_____/21:00078873 RIV/00216224:14110/21:00124279
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0145212621001855?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0145212621001855?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.leukres.2021.106684" target="_blank" >10.1016/j.leukres.2021.106684</a>
Alternative languages
Result language
angličtina
Original language name
Rituximab induces rapid blood repopulation by CLL cells mediated through their release from immune niches and complement exhaustion
Original language description
The in vivo rituximab effects in B cell malignancies are only partially understood. Here we analyzed in a large chronic lymphocytic leukemia (CLL) cohort (n = 80) the inter-patient variability in CLL cell count reduction within the first 24 h of rituximab administration in vivo, and a phenomenon of blood repopulation by malignant cells after anti-CD20 antibody therapy. Larger CLL cell elimination after rituximab infusion was associated with lower pre-therapy CLL cell counts, higher CD20 levels, and the non-exhausted capacity of complement dependent cytotoxicity (CDC). The absolute amount of cell-surface CD20 molecules (CD20 density x CLL lymphocytosis) was a predictor for complement exhaustion during therapy. We also describe that a highly variable decrease in CLL cell counts at 5 h (88 %-2%) following rituximab infusion is accompanied in most patients by peripheral blood repopulation with CLL cells at 24 h, and in similar to 20 % of patients, this resulted in CLL counts higher than before therapy. We provide evidence that CLL cells recrudescence is linked with i) CDC exhaustion, which leads to the formation of an insufficient amount of membrane attack complexes, likely resulting in temporary retention of surviving rituximab-opsonized cells by the mononuclear-phagocyte system (followed by their release back to blood), and ii) CLL cells regression from immune niches (CXCR4(dim)CD5(bright) intraclonal subpopulation). Patients with major peripheral blood CLL cell repopulation exhibited a longer time to-progression after chemoimmunotherapy compared to patients with lower or no repopulation, suggesting chemotherapy vulnerability of CLL cells that repopulate the blood.
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/GA20-02566S" target="_blank" >GA20-02566S: FOXO1-GAB1 AXIS AND MOLECULAR PATHWAYS GUIDING RE-CIRCULATION OF LEUKEMIC B CELLS TO IMMUNE NICHES: THERAPEUTIC IMPLICATIONS</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Leukemia Research
ISSN
0145-2126
e-ISSN
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Volume of the periodical
111
Issue of the periodical within the volume
DEC
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
106684
UT code for WoS article
000703570900003
EID of the result in the Scopus database
2-s2.0-85113289606