Anti-Glucosylsphingosine Autoimmunity, JAK2V617F-Dependent Interleukin-1β and JAK2V617F-Independent Cytokines in Myeloproliferative Neoplasms.
Fiche publication
Date publication
août 2020
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GIRODON François
Tous les auteurs :
Allain-Maillet S, Bosseboeuf A, Mennesson N, Bostoën M, Dufeu L, Choi EH, Cleyrat C, Mansier O, Lippert E, Le Bris Y, Gombert JM, Girodon F, Pettazzoni M, Bigot-Corbel E, Hermouet S
Lien Pubmed
Résumé
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.
Mots clés
CALR exon 9 mutants, CRISPR technology, IL-1Rα, IL-33, IP-10, JAK2V617F, UT-7, antigenic stimulation, auto-immunity, cytokines, glucolipids, glucosylsphingosine (GlcSph), inflammation, interleukin-1β (IL-1β), leptin, myeloproliferative neoplasms (MPNs)
Référence
Cancers (Basel). 2020 Aug 28;12(9):