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

Joanne Elliott1, Yvonne Suessmuth, Linda M Scott

  • 1Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, QUB, 2 floor, Whitla Medical Building, 97 Lisburn Rd, Belfast BT97BL, Northern Ireland.

Haematologica
|February 21, 2009
PubMed

Insights

Tyrosine phosphorylated SOCS3 indicates myeloproliferative neoplasms (MPNs) caused by JAK2 mutations. This phosphorylation may serve as a biomarker for MPNs and a reporter for JAK2 inhibitor therapy effectiveness.

Area of Science:

  • Molecular Biology
  • Oncology
  • Hematology

Background:

  • JAK2 V617F mutation is prevalent in myeloproliferative neoplasms (MPNs).
  • This mutation leads to tyrosine phosphorylation of SOCS3, enabling escape from inhibition.
  • JAK2 exon 12 mutations are found in V617F-negative MPN cases.

Purpose of the Study:

  • To investigate if JAK2 exon 12 mutants also stabilize tyrosine phosphorylated SOCS3.
  • To assess SOCS3 tyrosine phosphorylation in patients with specific JAK2 mutations.
  • To evaluate SOCS3 tyrosine phosphorylation as a potential biomarker for JAK2-mutated MPNs and therapy response.

Main Methods:

  • Analysis of SOCS3 tyrosine phosphorylation in cells expressing JAK2 exon 12 mutants.
  • Isolation and analysis of peripheral blood mononuclear cells and granulocytes from MPN patients.
  • Treatment of cells with JAK kinase inhibitors and assessment of JAK2 and SOCS3 phosphorylation levels.

Main Results:

  • JAK2 exon 12 mutants stabilize tyrosine phosphorylated SOCS3.
  • SOCS3 tyrosine phosphorylation is present in patients with JAK2 H538QK539L or JAK2 F537-K539delinsL mutations.
  • JAK kinase inhibitors reduce proliferation and dose-dependently decrease mutant JAK2 and SOCS3 tyrosine phosphorylation.

Conclusions:

  • Tyrosine phosphorylated SOCS3 is associated with JAK2 mutations in MPNs, including exon 12 variants.
  • SOCS3 tyrosine phosphorylation may serve as a novel biomarker for JAK2-mutated MPNs.
  • This phosphorylation could potentially report on the effectiveness of JAK2 inhibitor therapy.

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