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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F22%3A00127431" target="_blank" >RIV/00216224:14740/22:00127431 - isvavai.cz</a>

Alternative codes found

RIV/65269705:_____/22:00076462

Result on the web

<a href="https://ashpublications.org/bloodadvances/article/6/18/5494/485430/High-surface-IgM-levels-associate-with-shorter" target="_blank" >https://ashpublications.org/bloodadvances/article/6/18/5494/485430/High-surface-IgM-levels-associate-with-shorter</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1182/bloodadvances.2021006659" target="_blank" >10.1182/bloodadvances.2021006659</a>

Result language

angličtina

Original language name

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

Original language description

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 &lt; .0001). High sIgM levels/ signaling strongly correlated with short TTNT (P &lt; .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 &lt; .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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30205 - Hematology

Project

<a href="/en/project/GA20-02566S" target="_blank" >GA20-02566S: FOXO1-GAB1 AXIS AND MOLECULAR PATHWAYS GUIDING RE-CIRCULATION OF LEUKEMIC B CELLS TO IMMUNE NICHES: THERAPEUTIC IMPLICATIONS</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

BLOOD ADVANCES

ISSN

2473-9529

e-ISSN

—

Volume of the periodical

6

Issue of the periodical within the volume

18

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

11

Pages from-to

5494-5504

UT code for WoS article

000874686400027

EID of the result in the Scopus database

2-s2.0-85139452397