Revealing a Phenotypical Appearance of Ibrutinib Resistance in Patients With Chronic Lymphocytic Leukaemia by Flow Cytometry
Background: Ibrutinib is widely known as an effective and well-tolerated therapeutical choice of the chronic lymphocytic leukaemia (CLL). However, acquired resistance may occur during the treatment, causing relapse. Early detection of ibrutinib resistance is an important issue, therefore we aimed to...
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Published in | Pathology oncology research Vol. 28; p. 1610659 |
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Main Authors | , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
21.09.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Background:
Ibrutinib is widely known as an effective and well-tolerated therapeutical choice of the chronic lymphocytic leukaemia (CLL). However, acquired resistance may occur during the treatment, causing relapse. Early detection of ibrutinib resistance is an important issue, therefore we aimed to find phenotypic markers on CLL cells the expression of which may correlate with the appearance of ibrutinib resistance.
Methods:
We examined 28 patients’ peripheral blood (PB) samples (treatment naïve, ibrutinib sensitive, clinically ibrutinib resistant). The surface markers’ expression (CD27, CD69, CD86, CD184, CD185) were measured by flow cytometry. Furthermore, the BTK
C481S
resistance mutation was assessed by digital droplet PCR. Moreover, the CLL cells’ phenotype of a patient with acquired ibrutinib resistance was observed during the ibrutinib treatment.
Results:
The expression of CD27 (
p
= 0.030) and CD86 (
p
= 0.031) became higher in the clinically resistant cohort than in the ibrutinib sensitive cohort. Besides, we found that high CD86 and CD27 expressions were accompanied by BTK
C481S
mutation. Our prospective study showed that the increase of the expression of CD27, CD69 and CD86 was noticed ahead of the clinical resistance with 3 months.
Conclusion:
Our study suggests that the changes of the expression of these markers could indicate ibrutinib resistance and the examination of these phenotypic changes may become a part of the patients’ follow-up in the future. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ORCID: Ferenc Takács, orcid.org/0000-0001-8686-0295; Lili Kotmayer, orcid.org/0000-0002-5089-7659; Ágnes Czeti, orcid.org/0000-0001-5657-4167; Gábor Szalóki, orcid.org/0000-0001-6190-9128; Tamás László, orcid.org/0000-0003-3106-9951; Ágnes Márk, orcid.org/0000-0001-6190-9128; Gábor Barna, orcid.org/0000-0002-8895-3062 Edited by: Anna Sebestyén, Semmelweis University, Hungary |
ISSN: | 1532-2807 1219-4956 1532-2807 |
DOI: | 10.3389/pore.2022.1610659 |