Insight into the mechanism of CD34+ cell mobilisation impairment in multiple myeloma patients treated with anti-CD38 therapy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F24%3A10481280" target="_blank" >RIV/00179906:_____/24:10481280 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61988987:17110/24:A2502NIV RIV/00216208:11150/24:10481280 RIV/61989592:15110/24:73620478 RIV/00098892:_____/24:10158066 RIV/00843989:_____/24:E0110994

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=vz8XctiO4b" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=vz8XctiO4b</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/bjh.19141" target="_blank" >10.1111/bjh.19141</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Insight into the mechanism of CD34+ cell mobilisation impairment in multiple myeloma patients treated with anti-CD38 therapy

Popis výsledku v původním jazyce

Induction therapy followed by CD34(+) cell mobilisation and autologous transplantation represents standard of care for multiple myeloma (MM). However, the anti-CD38 monoclonal antibodies daratumumab and isatuximab have been associated with mobilisation impairment, yet the mechanism remains unclear. In this study, we investigated the effect of three different regimens (dara-VCd, isa-KRd and VTd) on CD34(+) cells using flow cytometry and transcriptomics. Decreased CD34(+) cell peak concentration and yields, longer collection and delayed engraftment were reproduced after dara-VCd/isa-KRd versus VTd induction in 34 patients in total. Using flow cytometry, we detected major changes in the proportion of apheresis product and bone marrow CD34+ subsets in patients treated with regimens containing anti-CD38 therapy; however, without any decrease in CD38high B-lymphoid progenitors in both materials. RNA-seq of mobilised CD34(+) cells from 21 patients showed that adhesion genes are overexpressed in CD34(+) cells after dara-VCd/isa-KRd and JCAD, NRP2, MDK, ITGA3 and CLEC3B were identified as potential target genes. Finally, direct in vitro effect of isatuximab in upregulating JCAD and CLEC3B was confirmed by quantitative PCR. These findings suggest that upregulated adhesion-related interactions, rather than killing of CD34(+) cells by effector mechanisms, could be leading causes of decreased mobilisation efficacy in MM patients treated with anti-CD38 therapy.

Název v anglickém jazyce

Insight into the mechanism of CD34+ cell mobilisation impairment in multiple myeloma patients treated with anti-CD38 therapy

Popis výsledku anglicky

Induction therapy followed by CD34(+) cell mobilisation and autologous transplantation represents standard of care for multiple myeloma (MM). However, the anti-CD38 monoclonal antibodies daratumumab and isatuximab have been associated with mobilisation impairment, yet the mechanism remains unclear. In this study, we investigated the effect of three different regimens (dara-VCd, isa-KRd and VTd) on CD34(+) cells using flow cytometry and transcriptomics. Decreased CD34(+) cell peak concentration and yields, longer collection and delayed engraftment were reproduced after dara-VCd/isa-KRd versus VTd induction in 34 patients in total. Using flow cytometry, we detected major changes in the proportion of apheresis product and bone marrow CD34+ subsets in patients treated with regimens containing anti-CD38 therapy; however, without any decrease in CD38high B-lymphoid progenitors in both materials. RNA-seq of mobilised CD34(+) cells from 21 patients showed that adhesion genes are overexpressed in CD34(+) cells after dara-VCd/isa-KRd and JCAD, NRP2, MDK, ITGA3 and CLEC3B were identified as potential target genes. Finally, direct in vitro effect of isatuximab in upregulating JCAD and CLEC3B was confirmed by quantitative PCR. These findings suggest that upregulated adhesion-related interactions, rather than killing of CD34(+) cells by effector mechanisms, could be leading causes of decreased mobilisation efficacy in MM patients treated with anti-CD38 therapy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

British Journal of Haematology

ISSN

0007-1048

e-ISSN

1365-2141

Svazek periodika

204

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

1439-1449

Kód UT WoS článku

001080973100001

EID výsledku v databázi Scopus

2-s2.0-85173937773