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However, the anti\u2010CD38 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\u2010VCd, isa\u2010KRd and VTd) on CD34<jats:sup>+<\/jats:sup> cells using flow cytometry and transcriptomics. Decreased CD34<jats:sup>+<\/jats:sup> cell peak concentration and yields, longer collection and delayed engraftment were reproduced after dara\u2010VCd\/isa\u2010KRd 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<jats:sup>+<\/jats:sup> subsets in patients treated with regimens containing anti\u2010CD38 therapy; however, without any decrease in CD38high B\u2010lymphoid progenitors in both materials. RNA\u2010seq of mobilised CD34<jats:sup>+<\/jats:sup> cells from 21 patients showed that adhesion genes are overexpressed in CD34<jats:sup>+<\/jats:sup> cells after dara\u2010VCd\/isa\u2010KRd and <jats:italic>JCAD<\/jats:italic>, <jats:italic>NRP2<\/jats:italic>, <jats:italic>MDK<\/jats:italic>, <jats:italic>ITGA3<\/jats:italic> and <jats:italic>CLEC3B<\/jats:italic> were identified as potential target genes. Finally, direct in vitro effect of isatuximab in upregulating <jats:italic>JCAD<\/jats:italic> and <jats:italic>CLEC3B<\/jats:italic> was confirmed by quantitative PCR<jats:italic>.<\/jats:italic> These findings suggest that upregulated adhesion\u2010related interactions, rather than killing of CD34<jats:sup>+<\/jats:sup> cells by effector mechanisms, could be leading causes of decreased mobilisation efficacy in MM patients treated with anti\u2010CD38 therapy.<\/jats:p>","DOI":"10.1111\/bjh.19141","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T01:33:41Z","timestamp":1697074421000},"page":"1439-1449","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Insight into the mechanism of <scp>CD34<\/scp><sup>+<\/sup> cell mobilisation impairment in multiple myeloma patients treated with <scp>anti\u2010CD38<\/scp> 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