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Impact of hydroxycarbamide and interferon-α on red cell adhesion and membrane protein expression in polycythemia vera.

Impact of hydroxycarbamide and interferon-α on red cell adhesion and membrane protein expression in polycythemia vera.
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Brusson M, De Grandis M, Cochet S, Bigot S, Marin M, Leduc M, Guillonneau F, Mayeux P, Peyrard T, Chomienne C, Le Van Kim C, Cassinat B, Kiladjian JJ, El Nemer W,


Brusson M, De Grandis M, Cochet S, Bigot S, Marin M, Leduc M, Guillonneau F, Mayeux P, Peyrard T, Chomienne C, Le Van Kim C, Cassinat B, Kiladjian JJ, El Nemer W, (click to view)

Brusson M, De Grandis M, Cochet S, Bigot S, Marin M, Leduc M, Guillonneau F, Mayeux P, Peyrard T, Chomienne C, Le Van Kim C, Cassinat B, Kiladjian JJ, El Nemer W,

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Haematologica 2018 03 29() pii 10.3324/haematol.2017.182303

Abstract

Polycythemia vera is a chronic myeloproliferative neoplasm characterized by the JAK2V617F mutation, elevated blood cell counts and a high risk of thrombosis. Although the red cell lineage is primarily affected by JAK2V617F, the impact of mutated JAK2 on circulating red blood cells is poorly documented. Recently, we showed that in polycythemia vera erythrocytes had abnormal expression of several proteins including Lu/BCAM adhesion molecule and proteins from the endoplasmic reticulum, mainly calreticulin and calnexin. Here, we investigated the effects of hydroxycarbamide and interferon-α treatments on the expression of erythroid membrane proteins in a cohort of 53 patients. Surprisingly, while both drugs tended to normalize calreticulin expression, proteomics analysis showed that hydroxycarbamide deregulated the expression of 53 proteins in red cell ghosts, with overexpression and down-regulation of 37 and 16 proteins, respectively. Within overexpressed proteins, hydroxycarbamide was found to enhance the expression of adhesion molecules such as Lu/BCAM and CD147, while interferon-α did not. In addition, we found that hydroxycarbamide increased Lu/BCAM phosphorylation and exacerbated red cell adhesion to its ligand laminin. Our study reveals unexpected adverse effects of hydroxycarbamide on red cell physiology in polycythemia vera and gives new insights into the effects of this molecule on gene regulation and protein recycling or maturation during erythroid differentiation. Furthermore, our study shows deregulation of Lu/BCAM and CD147 that are two ubiquitously expressed proteins linked to progression of solid tumors, paving the way to future studies to address the role of hydroxycarbamide in other tissues than blood cells in myeloproliferative neoplasms.

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