ALLAIN-MAILLET, Sophie; BOSSEBOEUF, Adrien; MENNESSON, Nicolas; BOSTOËN, Mégane; DUFEU, Laura; CHOI, Eun Ho; CLEYRAT, Cédric; MANSIER, Olivier; LIPPERT, Eric; LE BRIS, Yannick; GOMBERT, Jean-Marc; GIRODON, François; PETTAZZONI, Magali; BIGOT-CORBEL, Edith; HERMOUET, Sylvie

doi:10.3390/cancers12092446

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Article de revue

Ce document a été publié dans

Cancers. 2020-08-28, vol. 12, n° 9

Résumé en anglais

Inflammatory cytokines play a major role in myeloproliferative neoplasms (MPNs) as regulators of the MPN clone and as mediators of clinical symptoms and complications. Firstly, we investigated the effect of V617F on 42 molecules linked to inflammation. For V617F-mutated patients, the V617F allele burden (%V617F) correlated with the levels of IL-1β, IL-1Rα, IP-10 and leptin in polycythemia vera (PV), and with IL-33 in ET; for all other molecules, no correlation was found. Cytokine production was also studied in the human megakaryocytic cell line UT-7. Wild-type UT-7 cells secreted 27/42 cytokines measured. UT-7 clones expressing 50% or 75% V617F were generated, in which the production of IL-1β, IP-10 and RANTES was increased; other cytokines were not affected. Secondly, we searched for causes of chronic inflammation in MPNs other than driver mutations. Since antigen-driven selection is increasingly implicated in the pathogenesis of blood malignancies, we investigated whether proinflammatory glucosylsphingosine (GlcSph) may play a role in MPNs. We report that 20% (15/75) of MPN patients presented with anti-GlcSph IgGs, distinguished by elevated levels of 11 cytokines. In summary, only IL-1β and IP-10 were linked to V617F both in patients and in UT-7 cells; other inflammation-linked cytokines in excess in MPNs were not. For subsets of MPN patients, a possible cause of inflammation may be auto-immunity against glucolipids.< Réduire

Mots clés

article clinique

Mots clés en anglais

myeloproliferative neoplasms

inflammation

CALR exon 9 mutants; interleukin-1 (IL-1 )

cytokines

interleukin-1 (IL-1 )

IL-1R ; IP-10

leptin

IL-33

UT-7

CRISPR technology

antigenic stimulation

glucolipids

glucosylsphingosine (GlcSph)

auto-immunity

URI

https://oskar-bordeaux.fr/handle/20.500.12278/26090

DOI

http://dx.doi.org/10.3390/cancers12092446

Unités de recherche

Biologie des maladies cardiovasculaires (BMC) - UMR 1034

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Anti-Glucosylsphingosine Autoimmunity, JAK2V617F-Dependent Interleukin-1β and JAK2V617F-Independent Cytokines in Myeloproliferative Neoplasms.