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.

journal_name

Haematologica

journal_title

Haematologica

authors

Elliott J,Suessmuth Y,Scott LM,Nahlik K,McMullin MF,Constantinescu SN,Green AR,Johnston JA

doi

10.3324/haematol.2008.002352

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

576-80

issue

4

eissn

0390-6078

issn

1592-8721

pii

haematol.2008.002352

journal_volume

94

pub_type

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