Lu/BCAM‐mediated cell adhesion as biological marker of JAK2V617F activity in erythrocytes of polycythemia vera patients

Grandis, Maria De; Cassinat, Bruno; Kiladjian, Jean‐Jacques; Chomienne, Christine; Nemer, Wassim El

doi:10.1002/ajh.24023

Cited by 8 publications

(6 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a matter of fact, we have previously shown that PV RBC adhesion to laminin in UT patients was correlated with the JAK2V617F allele burden, defined as the percentage of circulating JAK2 alleles with the V617F mutation (%V617F). 26 We determined the %V617F of all patients and, as expected and as reported in previous studies, 13 the median was significantly lower in the IFN than in the UT and HC groups ( Figure 3B ). Moreover, we found no significant difference between the UT and the HC groups, despite a lower median in the latter ( Figure 3B ), indicating that increased RBC adhesion in the HC group was independent of the %V617F and was most probably due to the expression level of Lu/BCAM.…”

Section: Resultssupporting

confidence: 80%

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

et al. 2018

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 80%

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

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Of clinical interest is the observation that JAK inhibition blocked both this pathway and the adhesion of PV erythrocytes to laminin in functional flow assays in vitro. The same group has recently demonstrated a direct correlation between red cell adhesion and the JAK2V617F expression and propose using a functional red cell adhesion assay as a biomarker in PV . This work has shown that the red cell adhesion assay is a better biomarker of JAK2 mutation status, but the Lu expression is a marker associated with both JAK2‐mutated and wild‐type MPN.…”

Section: Discussionmentioning

confidence: 86%

Erythrocytes from patients with myeloproliferative neoplasms and splanchnic venous thrombosis show greater expression of Lu/BCAM

Novitzky‐Basso

Spring

Anstee

et al. 2018

Int J Lab Hematology

View full text Add to dashboard Cite

show abstract

“…An increase in RBC adhesion to endothelial cells was suggested by Wautier et al RBC's from patients with PV were associated with increased expression and phosphorylation of Lutheran blood group/basal cell adhesion molecule (Lu/BCAM) and adhesion (via Laminin) in an ex-vivo human umbilical vein endothelial cells (HUVECs) model [49]. The increase in Lu/BCAM was later suggested to be a cell-intrinsic property driven by JAK2 mutations [50]. Poisson et al described the contribution of erythrocyte-derived microvesicles (MV's) to arterial constriction and thrombosis in a murine model.…”

Section: Rbc's and Hematocritmentioning

confidence: 95%

“…RBC's-The RBC and platelets interact via FAS ligand/FAS receptor that result in the externalization of RBC phosphatidylserine (PS), promoting thrombin generation and thrombus formation [48]. Increased expression and phosphorylation of Lutheran blood group/basal cell adhesion molecule (Lu/BCAM) driven by JAK2 mutations [50] and adhesion (via Laminin) [49], mediate adhesion of RBC to endothelial cells. Erythrocyte-derived microvesicles (MV) contribute to arterial constriction and thrombosis mediated via oxidative stress and disruption of the nitric oxide (NO) pathway by the myeloperoxidase (MPO)-loaded MV's [51].…”

Section: Covid-19 Mpns and Thrombosis-(mechanistic) Lessons Learned From The Pandemicmentioning

confidence: 99%

Can Novel Insights into the Pathogenesis of Myeloproliferative Neoplasm-Related Thrombosis Inform Novel Treatment Approaches?

Wolach

Abulafia

2021

Hemato

View full text Add to dashboard Cite

Despite recent advances in diagnosis and therapy, arterial and venous thrombosis remain a major cause of morbidity and mortality in Philadelphia-negative myeloproliferative neoplasms (MPNs). Preventing and treating arterial and venous thrombosis represent one of the major goals in MPNs. The prothrombotic phenotype of MPNs is the result of a complex interplay between several components. Neutrophils, platelets, red blood cells (RBCs) and endothelial cells assume an activated phenotype in MPNs and undergo morphologic and metabolic changes that render these cells prothrombotic. These changes are in part the result of alterations induced by MPN initiating, driving mutations as well as the effect of extrinsic factors that stem from cell interactions as well as the inflammatory environment and rheological properties that characterize MPNs. In this review, we address current management issues in MPNs and provide an update on recent understanding of the pathogenesis of thrombosis in MPNs. We also address how lessons learned from other thrombo-inflammatory conditions can further inform and improve management of thrombosis in MPNs. Based on the above data and recent discoveries and developments, we discuss potential novel targets and therapeutic approaches to tackle the challenge of thrombosis in MPNs.

show abstract

Lu/BCAM‐mediated cell adhesion as biological marker of JAK2V617F activity in erythrocytes of polycythemia vera patients

Cited by 8 publications

References 6 publications

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

Erythrocytes from patients with myeloproliferative neoplasms and splanchnic venous thrombosis show greater expression of Lu/BCAM

Can Novel Insights into the Pathogenesis of Myeloproliferative Neoplasm-Related Thrombosis Inform Novel Treatment Approaches?

Contact Info

Product

Resources

About