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EVALUATION OF PLATELET RECEPTOR EXPRESSION IN CHRONIC LYMPHOID LEUKEMIA TREATED WITH IBRUTINIB
Author(s): ,
Viola Popov
Affiliations:
Hematology,Colentina Clinical Hospital,Bucharest,Romania
,
Ion Dumitru
Affiliations:
HEMATOLOGY,EMERGENCY UNIVERSITY HOSPITAL,Bucharest,Romania
,
Christien Oktaviani Matei
Affiliations:
Biophysics and Cellular Biotechnology ,UMF Carol Davila,Bucharest,Romania
,
Bogdan Mircea Matei
Affiliations:
Biophysics and Cellular Biotechnology,UMF Carol Davila,Bucharest,Romania
,
Meilin Omer
Affiliations:
Hematology,Colentina Clinical Hospital,Bucharest,Romania
,
Rebeca Leu
Affiliations:
Biophysics and Cellular Biotechnology ,Carol Davila University of Medicine and Pharmacy,Bucharest,Romania
,
Mihaela Georgeta Moisescu
Affiliations:
Biophysics and Cellular Biotechnology ,UMF Carol Davila,Bucharest,Romania
,
Tudor Savopol
Affiliations:
Biophysics and Cellular Biotechnology, Carol Davila University of Medicine and Pharmacy,Bucharest,Romania
,
Eugenia Kovacs
Affiliations:
Biophysics and Cellular Biotechnology ,Carol Davila University of Medicine and Pharmacy,Bucharest,Romania
Horia Bumbea
Affiliations:
Hematology Emergency University Hospital,UMF Carol Davila,Bucharest,Romania
(Abstract release date: 05/17/18) EHA Library. Bumbea H. 06/14/18; 216086; PB2359
Horia Bumbea
Horia Bumbea
Contributions
Abstract

Abstract: PB2359

Type: Publication Only

Background
Patients with chronic lymphoid leukemia (CLL) treated with Ibrutinib have increased bleeding risk. This complication is associated to platelets abnormalities. Platelet aggregation induced by different reagents is significantly decreased compared to controls. Ibrutinib inhibits platelet integrin αIIbβ3, outside-in signaling and thrombus stability. Membrane fluidity (MF) has an important role in the expression of platelet receptors and in modulating the activity of membrane proteins.

Aims
The aim of our study was to determine whether treatment with Ibrutinib influences the platelet MF and platelet receptor expression.

Methods
We present a retrospective study on 12 cases of CLL patients treated with Ibrutinib who were admitted in Colentina Clinical Hospital Bucharest, compared to a control group consisting in 10 untreated CLL patients. Platelet MF was measured by fluorescence anisotropy using TMA-DPH marker. Expression of platelet receptor was assessed by flowcytometry. We evaluated CD41/CD61 and CD42a/CD42b expression.

Results
Patients with CLL treated with Ibrutinib had a a higher platelet MF than in control group (p = 0.001). 3 CLL patients associated 17p mutation. In this group the level of MF was lower than in patients who had no 17p mutation, without statistical significance. The expression of CD41/CD61 and CD 42a/CD42b was lower in CLL group treated with Ibrutinib compared to untreated CLL patients group (p = 0.04). We also assessed the variation coefficient that represents the spread of intensity of fluorescence signal. This was higher in CLL patients group treated with Ibrutinib compared to control, for both types of analyzed receptors (CD41/CD61 and CD42a/CD42b). Our results confirm that MF and platelet receptors expression are influenced by Ibrutinib.

Conclusion
Administration of Ibrutinib in CLL patients is associated with higher MF and lower expression of platelet receptor with high spread of fluorescence. The modification of fluidity of platelet membrane probably could influence the expression of platelet receptors and quality of signaling. We have to check these findings on a larger group of CLL patients treated with Ibrutinib.

Session topic: 33.  Platelets disorders

Keyword(s): Chronic Lymphocytic Leukemia, flow cytometry, Platelet activation, Platelet aggregation

Abstract: PB2359

Type: Publication Only

Background
Patients with chronic lymphoid leukemia (CLL) treated with Ibrutinib have increased bleeding risk. This complication is associated to platelets abnormalities. Platelet aggregation induced by different reagents is significantly decreased compared to controls. Ibrutinib inhibits platelet integrin αIIbβ3, outside-in signaling and thrombus stability. Membrane fluidity (MF) has an important role in the expression of platelet receptors and in modulating the activity of membrane proteins.

Aims
The aim of our study was to determine whether treatment with Ibrutinib influences the platelet MF and platelet receptor expression.

Methods
We present a retrospective study on 12 cases of CLL patients treated with Ibrutinib who were admitted in Colentina Clinical Hospital Bucharest, compared to a control group consisting in 10 untreated CLL patients. Platelet MF was measured by fluorescence anisotropy using TMA-DPH marker. Expression of platelet receptor was assessed by flowcytometry. We evaluated CD41/CD61 and CD42a/CD42b expression.

Results
Patients with CLL treated with Ibrutinib had a a higher platelet MF than in control group (p = 0.001). 3 CLL patients associated 17p mutation. In this group the level of MF was lower than in patients who had no 17p mutation, without statistical significance. The expression of CD41/CD61 and CD 42a/CD42b was lower in CLL group treated with Ibrutinib compared to untreated CLL patients group (p = 0.04). We also assessed the variation coefficient that represents the spread of intensity of fluorescence signal. This was higher in CLL patients group treated with Ibrutinib compared to control, for both types of analyzed receptors (CD41/CD61 and CD42a/CD42b). Our results confirm that MF and platelet receptors expression are influenced by Ibrutinib.

Conclusion
Administration of Ibrutinib in CLL patients is associated with higher MF and lower expression of platelet receptor with high spread of fluorescence. The modification of fluidity of platelet membrane probably could influence the expression of platelet receptors and quality of signaling. We have to check these findings on a larger group of CLL patients treated with Ibrutinib.

Session topic: 33.  Platelets disorders

Keyword(s): Chronic Lymphocytic Leukemia, flow cytometry, Platelet activation, Platelet aggregation

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