title: SOCS3 tyrosine phosphorylation as a potential bio-marker for myeloproliferative neoplasms associated with mutant JAK2 kinases.
abstract: JAK2 V617F, identified in the majority of patients with myeloproliferative neoplasms, tyrosine phosphorylates SOCS3 and escapes its inhibition. Here, we demonstrate that the JAK2 exon 12 mutants described in a subset of V617F-negative MPN cases, also stabilize tyrosine phosphorylated SOCS3. SOCS3 tyrosine phosphorylation was also observed in peripheral blood mononuclear cells and granulocytes isolated from patients with JAK2 H538QK539L or JAK2 F537-K539delinsL mutations. JAK kinase inhibitors, which effectively inhibited the proliferation of cells expressing V617F or K539L, also caused a dose-dependent reduction in both mutant JAK2 and SOCS3 tyrosine phosphorylation. We propose, therefore, that SOCS3 tyrosine phosphorylation may be a novel bio-marker of myeloproliferative neoplasms resulting from a JAK2 mutation and a potential reporter of effective JAK2 inhibitor therapy currently in clinical development.
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, QUB, 2 floor, Whitla Medical Building, 97 Lisburn Rd, Belfast BT97BL, Northern Ireland.
authors.forename: Joanne
authors.initials: J
authors.lastname: Elliott
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Suessmuth
authors.forename: Linda M
authors.initials: LM
authors.lastname: Scott
authors.forename: Krystyna
authors.initials: K
authors.lastname: Nahlik
authors.forename: Mary Frances
authors.initials: MF
authors.lastname: McMullin
authors.forename: Stefan N
authors.initials: SN
authors.lastname: Constantinescu
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Green
authors.forename: James A
authors.initials: JA
authors.lastname: Johnston
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D002460:Cell Line; D049109:Cell Proliferation; D005091:Exons; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000175:diagnosis* / Q000235:genetics; D010766:Phosphorylation; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D013601:T-Lymphocytes; D014443:Tyrosine / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014443:Tyrosine; D053614:Janus Kinase 2