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.
Dopingem obecně rozumíme použití zakázaných látek sportovcem za účelem zvýšení sportovního výkonu. Podle oficiální definice jde o porušení antidopingových pravidel uvedených ve Světovém antidopingovém kodexu. Článek přináší stručný přehled v ČR registrovaných a obchodovaných humánních léčiv, která obsahují substance ze Seznamu zakázaných látek a metod Světové antidopingové agentury (WADA), doplněný o příklady dopingu z vrcholového sportu.
By doping, we usually mean the use of prohibited substances by an athlete for performance enhancement. Officially, it is a violation of the anti-doping rules specified in the World Anti-Doping Code. The article presents a brief overview of human medicines available in the Czech Republic that contain substances from the List of Prohibited Substances and Methods of the World Anti-Doping Agency (WADA). Examples of doping affairs of professional athletes are presented.
- MeSH
- anabolika MeSH
- doping ve sportu * MeSH
- léčivé přípravky MeSH
- lidé MeSH
- stimulancia terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
