B cell developmental trajectory modeling - using complex immunophenotype to identify pre-malignant CLL B cell subsets in peripheral blood of healthy donors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F21%3A00075046" target="_blank" >RIV/65269705:_____/21:00075046 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.conference.csac.cz/Amca-CSAC/media/content/2021/program/Book-of-abstracts-CSAC2021.pdf" target="_blank" >https://www.conference.csac.cz/Amca-CSAC/media/content/2021/program/Book-of-abstracts-CSAC2021.pdf</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

B cell developmental trajectory modeling - using complex immunophenotype to identify pre-malignant CLL B cell subsets in peripheral blood of healthy donors

Popis výsledku v původním jazyce

Chronic lymphocytic leukemia (CLL) is a common lymphoproliferative malignancy, often preceded by the pre-malignant state of monoclonal B-lymphocytosis (MBL). The origin of the disease - the cell of origin and the key initiating event - is currently unknown. Epigenetic, transcriptomic and immunophenotyping studies point to the fact that the disease originates in mature, antigen-experienced B-cells, most probably co-expressing CD27 and CD5. On the other hand, it was shown that the malignant clones share features of a whole continuum of B cell developmental trajectory, from naïve to memory B cells. We have therefore applied mass cytometry (cytometry by time-of-flight - CyTOF) and spectral flow cytometry approach to search for B-cell subsets within MBL and CLL-like phenotype in peripheral blood (PB) of heatlhy individuals. CyTOF methodology enabled us to perform immunophenotyping of complex B-cell samples from PB and bone marrow (BM) using a high number of markers, combining cell surface, intracellular and phosphorylated proteins and multiplexing of several samples in one run. The panel of markers was designed to distinguish normal and leukemic phenotype of B-cells and at the same time describe the B-cell maturation states. Multiplexing of B-cells isolated from BM and PB of healthy donors and PB of MBL and CLL patients was a key step for modeling of the developmental trajectories of normal B cells towards the malignant phenotype. This analysis successfully reconstructed the most probable trajectories of CLL development from normal mature B-cell counterparts via MBL and we were able to distinguish rare B-cell subsets with MBL and CLL-like phenotype in healthy individuals. Subsequently, we screened these cell populations in a larger cohort of healthy donor samples using spectral cytometry.

Název v anglickém jazyce

B cell developmental trajectory modeling - using complex immunophenotype to identify pre-malignant CLL B cell subsets in peripheral blood of healthy donors

Popis výsledku anglicky

Chronic lymphocytic leukemia (CLL) is a common lymphoproliferative malignancy, often preceded by the pre-malignant state of monoclonal B-lymphocytosis (MBL). The origin of the disease - the cell of origin and the key initiating event - is currently unknown. Epigenetic, transcriptomic and immunophenotyping studies point to the fact that the disease originates in mature, antigen-experienced B-cells, most probably co-expressing CD27 and CD5. On the other hand, it was shown that the malignant clones share features of a whole continuum of B cell developmental trajectory, from naïve to memory B cells. We have therefore applied mass cytometry (cytometry by time-of-flight - CyTOF) and spectral flow cytometry approach to search for B-cell subsets within MBL and CLL-like phenotype in peripheral blood (PB) of heatlhy individuals. CyTOF methodology enabled us to perform immunophenotyping of complex B-cell samples from PB and bone marrow (BM) using a high number of markers, combining cell surface, intracellular and phosphorylated proteins and multiplexing of several samples in one run. The panel of markers was designed to distinguish normal and leukemic phenotype of B-cells and at the same time describe the B-cell maturation states. Multiplexing of B-cells isolated from BM and PB of healthy donors and PB of MBL and CLL patients was a key step for modeling of the developmental trajectories of normal B cells towards the malignant phenotype. This analysis successfully reconstructed the most probable trajectories of CLL development from normal mature B-cell counterparts via MBL and we were able to distinguish rare B-cell subsets with MBL and CLL-like phenotype in healthy individuals. Subsequently, we screened these cell populations in a larger cohort of healthy donor samples using spectral cytometry.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30204 - Oncology

Projekt

<a href="/cs/project/NU20-08-00314" target="_blank" >NU20-08-00314: Single cell analýza: moderní nástroj pro studium klonální evoluce u pacientů s chronickou lymfocytární leukémií s vysokým rizikem</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů