Does increasing the JAK2V617F assay sensitivity allow to identify more patients with MPN?

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 downregulation of 37 and 16 proteins, respectively. Within over-expressed 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 provides 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 for future studies to address the role of hydroxycarbamide in tissues other than blood cells in myeloproliferative neoplasms.

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“…The percentage of the JAK2V617F allele was determined in DNA extracted from whole blood using the Mutaquant® (Ipsogen) method as described. 22 …”

Section: Methodsmentioning

confidence: 99%

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

et al. 2018

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“…Diagnosis was PV ( n = 10), ET ( n = 12), PMF ( n = 5) or suspicion of latent MPN revealed by SVT ( n = 23) among which six presented with a Budd‐Chiari Syndrom and 17 with Portal Vein thrombosis. The detection of JAK2 V617F, JAK2 exon 12 or MPL mutations was performed on DNA extracted from peripheral blood leucocytes as previously described (Kouroupi et al , ). The entire coding sequence of TET2 (11 exons) was analysed by direct Sanger sequencing.…”

Section: Clinical and Biological Characteristics Of The Five Patientsmentioning

confidence: 99%