• Je něco špatně v tomto záznamu ?

High surface IgM levels associate with shorter response to ibrutinib and BTK bypass in patients with CLL

G. Chiodin, S. Drennan, EA. Martino, L. Ondrisova, I. Henderson, L. Del Rio, I. Tracy, A. D'Avola, H. Parker, S. Bonfiglio, L. Scarfò, LA. Sutton, JC. Strefford, J. Forster, O. Brake, KN. Potter, B. Sale, S. Lanham, M. Mraz, P. Ghia, FK....

. 2022 ; 6 (18) : 5494-5504. [pub] 20220927

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22024340

Chronic lymphocytic leukemia (CLL) cells have variably low surface IgM (sIgM) levels/signaling capacity, influenced by chronic antigen engagement at tissue sites. Within these low levels, CLL with relatively high sIgM (CLLhigh) progresses more rapidly than CLL with low sIgM (CLLlow). During ibrutinib therapy, surviving CLL cells redistribute into the peripheral blood and can recover sIgM expression. Return of CLL cells to tissue may eventually recur, where cells with high sIgM could promote tumor growth. We analyzed time to new treatment (TTNT) following ibrutinib in 70 patients with CLL (median follow-up of 66 months) and correlated it with pretreatment sIgM levels and signaling characteristics. Pretreatment sIgM levels correlated with signaling capacity, as measured by intracellular Ca2+ mobilization (iCa2+), in vitro (r = 0.70; P < .0001). High sIgM levels/signaling strongly correlated with short TTNT (P < .05), and 36% of patients with CLLhigh vs 8% of patients with CLLlow progressed to require a new treatment. In vitro, capacity of ibrutinib to inhibit sIgM-mediated signaling inversely correlated with pretherapy sIgM levels (r = -0.68; P = .01) or iCa2+ (r = -0.71; P = .009). In patients, sIgM-mediated iCa2+ and ERK phosphorylation levels were reduced by ibrutinib therapy but not abolished. The residual signaling capacity downstream of BTK was associated with high expression of sIgM, whereas it was minimal when sIgM expression was low (P < .05). These results suggested that high sIgM levels facilitated CLL cell resistance to ibrutinib in patients. The CLL cells, surviving in the periphery with high sIgM expression, include a dangerous fraction that is able to migrate to tissue and receive proliferative stimuli, which may require targeting by combined approaches.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22024340
003      
CZ-PrNML
005      
20221031100817.0
007      
ta
008      
221017s2022 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1182/bloodadvances.2021006659 $2 doi
035    __
$a (PubMed)35640238
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Chiodin, Giorgia $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom $1 https://orcid.org/0000000214568997
245    10
$a High surface IgM levels associate with shorter response to ibrutinib and BTK bypass in patients with CLL / $c G. Chiodin, S. Drennan, EA. Martino, L. Ondrisova, I. Henderson, L. Del Rio, I. Tracy, A. D'Avola, H. Parker, S. Bonfiglio, L. Scarfò, LA. Sutton, JC. Strefford, J. Forster, O. Brake, KN. Potter, B. Sale, S. Lanham, M. Mraz, P. Ghia, FK. Stevenson, F. Forconi
520    9_
$a Chronic lymphocytic leukemia (CLL) cells have variably low surface IgM (sIgM) levels/signaling capacity, influenced by chronic antigen engagement at tissue sites. Within these low levels, CLL with relatively high sIgM (CLLhigh) progresses more rapidly than CLL with low sIgM (CLLlow). During ibrutinib therapy, surviving CLL cells redistribute into the peripheral blood and can recover sIgM expression. Return of CLL cells to tissue may eventually recur, where cells with high sIgM could promote tumor growth. We analyzed time to new treatment (TTNT) following ibrutinib in 70 patients with CLL (median follow-up of 66 months) and correlated it with pretreatment sIgM levels and signaling characteristics. Pretreatment sIgM levels correlated with signaling capacity, as measured by intracellular Ca2+ mobilization (iCa2+), in vitro (r = 0.70; P < .0001). High sIgM levels/signaling strongly correlated with short TTNT (P < .05), and 36% of patients with CLLhigh vs 8% of patients with CLLlow progressed to require a new treatment. In vitro, capacity of ibrutinib to inhibit sIgM-mediated signaling inversely correlated with pretherapy sIgM levels (r = -0.68; P = .01) or iCa2+ (r = -0.71; P = .009). In patients, sIgM-mediated iCa2+ and ERK phosphorylation levels were reduced by ibrutinib therapy but not abolished. The residual signaling capacity downstream of BTK was associated with high expression of sIgM, whereas it was minimal when sIgM expression was low (P < .05). These results suggested that high sIgM levels facilitated CLL cell resistance to ibrutinib in patients. The CLL cells, surviving in the periphery with high sIgM expression, include a dangerous fraction that is able to migrate to tissue and receive proliferative stimuli, which may require targeting by combined approaches.
650    _2
$a adenin $x analogy a deriváty $7 D000225
650    _2
$a vápník $7 D002118
650    _2
$a lidé $7 D006801
650    _2
$a imunoglobulin M $7 D007075
650    12
$a chronická lymfatická leukemie $x metabolismus $7 D015451
650    _2
$a piperidiny $7 D010880
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Drennan, Samantha $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom $u T-Cypher Bio, Oxford, United Kingdom
700    1_
$a Martino, Enrica A $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom $u Department of Haematology, Azienda Ospedaliera di Cosenza, Cosenza, Italy
700    1_
$a Ondrisova, Laura $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom $u Molecular Medicine, CEITEC Masaryk University, Brno, Czech Republic $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
700    1_
$a Henderson, Isla $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
700    1_
$a Del Rio, Luis $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom $1 https://orcid.org/0000000259269448
700    1_
$a Tracy, Ian $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
700    1_
$a D'Avola, Annalisa $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom $u The Francis Crick Institute, London, United Kingdom
700    1_
$a Parker, Helen $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
700    1_
$a Bonfiglio, Silvia $u Strategic Research Program on CLL and B-cell Neoplasia Unit, Experimental Oncology, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy
700    1_
$a Scarfò, Lydia $u Strategic Research Program on CLL and B-cell Neoplasia Unit, Experimental Oncology, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy $1 https://orcid.org/0000000208440989
700    1_
$a Sutton, Lesley-Ann $u Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; and
700    1_
$a Strefford, Jonathan C $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom $1 https://orcid.org/0000000209722881
700    1_
$a Forster, Jade $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
700    1_
$a Brake, Oliver $u Haematology Department, Cancer Care Directorate, University Hospital Southampton NHS Trust, Southampton, United Kingdom
700    1_
$a Potter, Kathleen N $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
700    1_
$a Sale, Benjamin $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom $1 https://orcid.org/0000000332921886
700    1_
$a Lanham, Stuart $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom $1 https://orcid.org/000000024516264X
700    1_
$a Mraz, Marek $u Molecular Medicine, CEITEC Masaryk University, Brno, Czech Republic $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic $1 https://orcid.org/0000000169758838
700    1_
$a Ghia, Paolo $u Strategic Research Program on CLL and B-cell Neoplasia Unit, Experimental Oncology, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy $1 https://orcid.org/0000000337507342
700    1_
$a Stevenson, Freda K $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
700    1_
$a Forconi, Francesco $u School of Cancer Sciences, Cancer Research UK and NIHR Experimental Cancer Medicine Centres, Faculty of Medicine, University of Southampton, Southampton, United Kingdom $u Haematology Department, Cancer Care Directorate, University Hospital Southampton NHS Trust, Southampton, United Kingdom $1 https://orcid.org/0000000222111831
773    0_
$w MED00194912 $t Blood advances $x 2473-9537 $g Roč. 6, č. 18 (2022), s. 5494-5504
856    41
$u https://pubmed.ncbi.nlm.nih.gov/35640238 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20221017 $b ABA008
991    __
$a 20221031100815 $b ABA008
999    __
$a ok $b bmc $g 1854199 $s 1175630
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2022 $b 6 $c 18 $d 5494-5504 $e 20220927 $i 2473-9537 $m Blood advances $n Blood Adv $x MED00194912
LZP    __
$a Pubmed-20221017

Najít záznam

Citační ukazatele

Možnosti archivace