Lack of interferon‐α‐induced tyrosine phosphorylation of Vav proto‐oncogene in patients with myelofibrosis with myeloid metaplasia

Myelofibrosis with myeloid metaplasia (MMM) is an uncommon chronic myeloproliferative disorder characterized by clonal stem cell proliferation and reactive non‐clonal proliferation of bone marrow fibroblasts with fibrosis. In the absence of curative therapy, the current management for the majority of patients is directed towards alleviation of symptoms and improvement in quality of life. A number of experimental therapies have been investigated, among which is the use of type I interferon (IFN)‐α, whose overall results are disappointing. We recently showed that the Vav proto‐oncogene product, p95Vav, which is phosphorylated under IFN‐α treatment, associates with both chains that constitute the functional type I IFN receptor and contributes to the antiproliferative effects of IFN‐α. The involvement of p95Vav in IFN‐α signalling and the frequent non‐responsiveness of patients to IFN‐α led us to investigate for any functional defect(s) of Vav in response to IFN in MMM patients. Our results showed that in the majority of patients Vav is constitutively hyperphosphorylated and that IFN‐α failed to increase substantially such a tyrosine phosphorylation of p95Vav.

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