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Insight into the mechanism of CD34+ cell mobilisation impairment in multiple myeloma patients treated with anti-CD38 therapy
O. Venglar, V. Kapustova, A. Anilkumar Sithara, D. Zihala, L. Muronova, T. Sevcikova, J. Vrana, A. Vdovin, J. Radocha, P. Krhovska, M. Hrdinka, M. Turjap, T. Popkova, Z. Chyra, L. Broskevicova, M. Simicek, Z. Koristek, R. Hajek, T. Jelinek
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
PubMed
37807708
DOI
10.1111/bjh.19141
Knihovny.cz E-zdroje
- MeSH
- antigeny CD34 analýza MeSH
- antigeny CD38 MeSH
- kostní dřeň chemie MeSH
- lidé MeSH
- mnohočetný myelom * terapie MeSH
- mobilizace hematopoetických kmenových buněk MeSH
- průtoková cytometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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.
Clinical Trials Section of Pharmacy University Hospital Ostrava Ostrava Czech Republic
Department of Hematooncology Faculty of Medicine University of Ostrava Ostrava Czech Republic
Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic
Faculty of Science University of Ostrava Ostrava Czech Republic
Citace poskytuje Crossref.org
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- $a 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.
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