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

J 2022

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

CHIODIN, Giorgia; Samantha DRENNAN; Enrica A MARTINO; Laura ONDRIŠOVÁ; Isla HENDERSON et al.

Základní údaje

Originální název

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

Autoři

Vydání

BLOOD ADVANCES, WASHINGTON, AMER SOC HEMATOLOGY, 2022, 2473-9529

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30205 Hematology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.600

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/22:00127431

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

CHRONIC LYMPHOCYTIC-LEUKEMIAB-CELL RECEPTORCD38 EXPRESSIONRESISTANCEACTIVATIONPCI-32765IMMUNOGLOBULININHIBITIONMUTATIONSPATHWAYS

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 1. 2023 09:29, Mgr. Tereza Miškechová

Anotace

V originále

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.

Citovat

CHIODIN, Giorgia; Samantha DRENNAN; Enrica A MARTINO; Laura ONDRIŠOVÁ; Isla HENDERSON; del Rio LUIS; Ian TRACY; Annalisa D'AVOLA; Helen PARKER; Silvia BONFIGLIO; Lydia SCARF; Lesley-Ann SUTTON; Jonathan C STREFFORD; Jade FORSTER; Oliver BRAKE; Kathleen N POTTER; Benjamin SALE; Stuart LANHAM; Marek MRÁZ; Paolo GHIA; Freda K STEVENSON a Francesco FORCONI. High surface IgM levels associate with shorter response to ibrutinib and BTK bypass in patients with CLL. BLOOD ADVANCES. WASHINGTON: AMER SOC HEMATOLOGY, 2022, roč. 6, č. 18, s. 5494-5504. ISSN 2473-9529. Dostupné z: https://doi.org/10.1182/bloodadvances.2021006659.

@article{2239433,
   author = {Chiodin, Giorgia and Drennan, Samantha and Martino, Enrica A and Ondrišová, Laura and Henderson, Isla and Luis, del Rio and Tracy, Ian and D'Avola, Annalisa and Parker, Helen and Bonfiglio, Silvia and Scarf, Lydia and Sutton, LesleyandAnn and Strefford, Jonathan C and Forster, Jade and Brake, Oliver and Potter, Kathleen N and Sale, Benjamin and Lanham, Stuart and Mráz, Marek and Ghia, Paolo and Stevenson, Freda K and Forconi, Francesco},
   article_location = {WASHINGTON},
   article_number = {18},
   doi = {https://doi.org/10.1182/bloodadvances.2021006659},
   keywords = {CHRONIC LYMPHOCYTIC-LEUKEMIAB-CELL RECEPTORCD38 EXPRESSIONRESISTANCEACTIVATIONPCI-32765IMMUNOGLOBULININHIBITIONMUTATIONSPATHWAYS},
   language = {eng},
   issn = {2473-9529},
   journal = {BLOOD ADVANCES},
   title = {High surface IgM levels associate with shorter response to ibrutinib and BTK bypass in patients with CLL},
   url = {https://ashpublications.org/bloodadvances/article/6/18/5494/485430/High-surface-IgM-levels-associate-with-shorter},
   volume = {6},
   year = {2022}
}

TY  - JOUR
ID  - 2239433
AU  - Chiodin, Giorgia - Drennan, Samantha - Martino, Enrica A - Ondrišová, Laura - Henderson, Isla - Luis, del Rio - Tracy, Ian - D'Avola, Annalisa - Parker, Helen - Bonfiglio, Silvia - Scarf, Lydia - Sutton, Lesley-Ann - Strefford, Jonathan C - Forster, Jade - Brake, Oliver - Potter, Kathleen N - Sale, Benjamin - Lanham, Stuart - Mráz, Marek - Ghia, Paolo - Stevenson, Freda K - Forconi, Francesco
PY  - 2022
TI  - High surface IgM levels associate with shorter response to ibrutinib and BTK bypass in patients with CLL
JF  - BLOOD ADVANCES
VL  - 6
IS  - 18
SP  - 5494-5504
EP  - 5494-5504
PB  - AMER SOC HEMATOLOGY
SN  - 24739529
KW  - CHRONIC LYMPHOCYTIC-LEUKEMIAB-CELL RECEPTORCD38 EXPRESSIONRESISTANCEACTIVATIONPCI-32765IMMUNOGLOBULININHIBITIONMUTATIONSPATHWAYS
UR  - https://ashpublications.org/bloodadvances/article/6/18/5494/485430/High-surface-IgM-levels-associate-with-shorter
N2  - 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.
ER  -

CHIODIN, Giorgia; Samantha DRENNAN; Enrica A MARTINO; Laura ONDRIŠOVÁ; Isla HENDERSON; del Rio LUIS; Ian TRACY; Annalisa D'AVOLA; Helen PARKER; Silvia BONFIGLIO; Lydia SCARF; Lesley-Ann SUTTON; Jonathan C STREFFORD; Jade FORSTER; Oliver BRAKE; Kathleen N POTTER; Benjamin SALE; Stuart LANHAM; Marek MRÁZ; Paolo GHIA; Freda K STEVENSON a Francesco FORCONI. High surface IgM levels associate with shorter response to ibrutinib and BTK bypass in patients with CLL. \textit{BLOOD ADVANCES}. WASHINGTON: AMER SOC HEMATOLOGY, 2022, roč.~6, č.~18, s.~5494-5504. ISSN~2473-9529. Dostupné z: https://doi.org/10.1182/bloodadvances.2021006659.

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