OCT 30, 2014 06:00 AM PDT

Epigenetic Dysregulation in the Pathogenesis of Myeloproliferative Neoplasms

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  • Assistant Professor, Biomedical Diagnostic & Therapeutic Sciences, , Oakland University
      Kristin Landis-Piwowar is an Assistant Professor of Biomedical Diagnostic and Therapeutic Sciences at Oakland University in Rochester, MI. She earned a bachelors degree from Ferris State University in Medical Technology, a Masters degree in Clinical Laboratory Science from Michigan State University and a PhD in Cancer Biology from Wayne State Universitys School of Medicine in the laboratory of Q. Ping Dou. Landis-Piwowar was awarded a post-doctoral fellowship at the University of Michigan, Department of Pathology, where she conducted research to understand CD30 signaling to NFkB in anaplastic large cell lymphoma. Landis-Piwowar joined the faculty at Oakland University in Rochester, MI where she currently holds rank as an Assistant Professor of Biomedical Diagnostic and Therapeutic Sciences. Landis-Piwowar has published more than 25 peer-reviewed journal articles on cancer therapeutics, prevention, and mechanisms of disease and has authored numerous book chapters. Her research interests are centered on the physiologic effects of gold-peptidomimetics in cancer cells, and deciphering a familial relationship among chronic lymphocytic leukemia and hairy cell leukemia.


    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.

    Learning Objectives:
    1. Define epigenetics
    2. Correlate the impact of somatic mutations and epigenetic control of gene expression with MPNs
    3. Identify therapeutic approaches designed for epigenetics

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