SOCS3 tyrosine phosphorylation as a potential bio-marker for myeloproliferative neoplasms associated with mutant JAK2 kinases

Joanne Elliott, Y. Suessmuth, L.M. Scott, Krystyna Nahlik, Mary Frances McMullin, S.N. Constantinescu, A.R. Green, James Johnston

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17 Citations (Scopus)

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 JAY2 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.
Original languageEnglish
Pages (from-to)576-580
Number of pages5
JournalHAEMATOLOGICA
Volume94
Issue number4
DOIs
Publication statusPublished - Apr 2009

ASJC Scopus subject areas

  • Hematology

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    Elliott, J., Suessmuth, Y., Scott, L. M., Nahlik, K., McMullin, M. F., Constantinescu, S. N., Green, A. R., & Johnston, J. (2009). SOCS3 tyrosine phosphorylation as a potential bio-marker for myeloproliferative neoplasms associated with mutant JAK2 kinases. HAEMATOLOGICA, 94(4), 576-580. https://doi.org/10.3324/haematol.2008.002352