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Kristin Landis Piwowar - Epigenetic Dysregulation in the Pathogenesis of Myeloproliferative Neoplasm
Watch on LabRoots at http://labroots.com/user/webinars/details/id/395
When the BCR/ABL1 fusion protein was identified in chronic myelogenous leukemia and the JAK2 V617F mutation was identified in patients with other myeloproliferative neoplasms (MPNs) such as polycythemia vera and essential thrombocythemia, tyrosine kinase activation appeared to be the principal driver of MPN pathogenesis. This notion of tyrosine kinase activation was further substantiated as genomic studies revealed multiple recurrent somatic mutations (e.g. MPL and LNK) in MPNs in the last decade. Yet many patients are diagnosed with an MPN lacking those particular driver mutations. Several mutations in molecules have since been identified that modify the epigenome (e.g. ASXL1, TET2, andEZH2) and many are likely to occur prior to JAK2 mutations and contribute to leukemogenesis. Mutant JAK2 has even been implicated as an epigenetic regulator. The relevance of these epigenetic disease alleles remains an important area of investigation. This session will discuss the molecular biology of epigenetics, the pathophysiology and clinical relevance of epigenetics and treatment options that target epigenetic modulators in the context of MPN.
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