Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

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

. 2024 ; 204 (4) : 1439-1449. [pub] 20231009

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24014509

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24014509
003      
CZ-PrNML
005      
20240905133955.0
007      
ta
008      
240725s2024 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1111/bjh.19141 $2 doi
035    __
$a (PubMed)37807708
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Venglar, Ondrej $u Faculty of Science, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic $1 https://orcid.org/0000000206199861
245    10
$a Insight into the mechanism of CD34+ cell mobilisation impairment in multiple myeloma patients treated with anti-CD38 therapy / $c 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
520    9_
$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.
650    _2
$a lidé $7 D006801
650    12
$a mnohočetný myelom $x terapie $7 D009101
650    _2
$a antigeny CD34 $x analýza $7 D018952
650    _2
$a kostní dřeň $x chemie $7 D001853
650    _2
$a průtoková cytometrie $7 D005434
650    _2
$a mobilizace hematopoetických kmenových buněk $7 D019650
650    _2
$a antigeny CD38 $7 D051997
655    _2
$a časopisecké články $7 D016428
700    1_
$a Kapustova, Veronika $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Anilkumar Sithara, Anjana $u Faculty of Science, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Zihala, David $u Faculty of Science, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Muronova, Ludmila $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Sevcikova, Tereza $u Faculty of Science, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Vrana, Jan $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Vdovin, Alexander $u Faculty of Science, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Radocha, Jakub $u 4th Department of Internal Medicine - Hematology, Charles University and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic
700    1_
$a Krhovska, Petra $u Department of Hematooncology, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, Olomouc, Czech Republic
700    1_
$a Hrdinka, Matous $u Faculty of Science, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Turjap, Michal $u Clinical Trials Section of Pharmacy, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Popkova, Tereza $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic $1 https://orcid.org/0000000158854218
700    1_
$a Chyra, Zuzana $u Faculty of Science, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Broskevicova, Lucie $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Simicek, Michal $u Faculty of Science, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Koristek, Zdenek $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic
700    1_
$a Hajek, Roman $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic $1 https://orcid.org/0000000169556267 $7 nlk20000083645
700    1_
$a Jelinek, Tomas $u Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic $u Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic $1 https://orcid.org/0000000254679253
773    0_
$w MED00009374 $t British journal of haematology $x 1365-2141 $g Roč. 204, č. 4 (2024), s. 1439-1449
856    41
$u https://pubmed.ncbi.nlm.nih.gov/37807708 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20240725 $b ABA008
991    __
$a 20240905133949 $b ABA008
999    __
$a ok $b bmc $g 2143955 $s 1226375
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 204 $c 4 $d 1439-1449 $e 20231009 $i 1365-2141 $m British journal of haematology $n Br J Haematol $x MED00009374
LZP    __
$a Pubmed-20240725

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...