Revealing a Phenotypical Appearance of Ibrutinib Resistance in Patients With Chronic Lymphocytic Leukaemia by Flow Cytometry.

Autor:	Takács F; Department of Pathology and Experimental Cancer Research, HCEMM-SE Molecular Oncohematology Research Group, Semmelweis University, Budapest, Hungary.; Center for Pathology, University Medical Center-University of Freiburg, Freiburg, Germany., Kotmayer L; Department of Pathology and Experimental Cancer Research, HCEMM-SE Molecular Oncohematology Research Group, Semmelweis University, Budapest, Hungary., Czeti Á; Department of Pathology and Experimental Cancer Research, HCEMM-SE Molecular Oncohematology Research Group, Semmelweis University, Budapest, Hungary., Szalóki G; Department of Pathology and Experimental Cancer Research, HCEMM-SE Molecular Oncohematology Research Group, Semmelweis University, Budapest, Hungary., László T; Department of Pathology and Experimental Cancer Research, HCEMM-SE Molecular Oncohematology Research Group, Semmelweis University, Budapest, Hungary., Mikala G; South-Pest Central Hospital-National Institute for Hematology and Infectious Diseases, Budapest, Hungary., Márk Á; Department of Pathology and Experimental Cancer Research, HCEMM-SE Molecular Oncohematology Research Group, Semmelweis University, Budapest, Hungary., Masszi A; Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary., Farkas P; Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary., Plander M; Department of Hematology, Markusovszky University Teaching Hospital, Szombathely, Hungary., Weisinger J; Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary., Demeter J; Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary., Fekete S; South-Pest Central Hospital-National Institute for Hematology and Infectious Diseases, Budapest, Hungary., Szerafin L; Hospitals of Szabolcs-Szatmár-Bereg County and University Teaching Hospital, Nyíregyháza, Hungary., Deák BM; National Institute of Oncology, Budapest, Hungary., Szaleczky E; National Institute of Oncology, Budapest, Hungary., Sulák A; 2nd Department of Internal Medicine and Cardiology Center, University of Szeged, Szeged, Hungary., Borbényi Z; 2nd Department of Internal Medicine and Cardiology Center, University of Szeged, Szeged, Hungary., Barna G; Department of Pathology and Experimental Cancer Research, HCEMM-SE Molecular Oncohematology Research Group, Semmelweis University, Budapest, Hungary.
Jazyk:	angličtina
Zdroj:	Pathology oncology research : POR [Pathol Oncol Res] 2022 Sep 21; Vol. 28, pp. 1610659. Date of Electronic Publication: 2022 Sep 21 (Print Publication: 2022).
DOI:	10.3389/pore.2022.1610659
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Takács, Kotmayer, Czeti, Szalóki, László, Mikala, Márk, Masszi, Farkas, Plander, Weisinger, Demeter, Fekete, Szerafin, Deák, Szaleczky, Sulák, Borbényi and Barna.)
Databáze:	MEDLINE
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