Myeloproliferative Neoplasms Associated with Mutation in JAK۲V۶۱۷F and Tyrosine Kinase Inhibitors as Therapeutic Strategy

MPNs including a heterogeneous group of clonal or oligoclonal hamtopathies characterized by proliferation and accumulation of mature myeloid cells. JAK۲ tyrosine kinase mutation is the most common molecular lesion identified in ۹۰% of cases. JAK۲ is involved in EPO signaling pathway, and mutations in it lead to EPO-independent spontaneous phosphorylation. Most tyrosine kinase inhibitors (TKI) are small molecules that compete with ATP for binding the ATP-binding site in tyrosine kinase domains, since ATP is a source of phosphate groups used by Tks to phosphorylate the target protein.there are many TKI agent that are studing for treatment of the MPNs with JAK۲ tyrosine kinase mutation.the most important TKI drugs including CEP۷۰۱, CYT۳۸۷, LY۲۷۸۴۵۴۴, SB۱۵۱۸, TG۱۰۱۳۴۸, XL۰۱۹, INCB۱۸۴۲۴. Most important mechanism of them are reduse the splenomegaly, improvement of constitutional symptoms(improvement of bone marrow fibrosis and anemia). Although this drugs are useful but they have some side effect that common of them including Gastrointestinal disease (GI), diarrhea, nausea and vomiting, anemia, thrombocytopenia, thrombosis, leukocytosis, thrombocytosis, peripheral neuropathy, transient loss of blood pressure and lightheadedness.

کلیدواژه ها:

MPN ، JAK۲ ، TKI