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

Result code in 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>

Alternative codes found

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

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30205 - Hematology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

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

Name of the periodical

British Journal of Haematology

ISSN

0007-1048

e-ISSN

1365-2141

Volume of the periodical

204

Issue of the periodical within the volume

4

Country of publishing house

GB - UNITED KINGDOM

Number of pages

11

Pages from-to

1439-1449

UT code for WoS article

001080973100001

EID of the result in the Scopus database

2-s2.0-85173937773