MARIA (KEN) FIGUEROA (MIAMI)
EPIGENETIC ABNORMALITIES IN MDS AND THEIR RELATIONSHIP WITH SOMATIC
MUTATIONS
Maria E. Figueroa, M.D.
Myelodysplastic syndromes (MDS) are a clinically and cytogenetically heterogeneous group of clonal
diseases characterized by ineffective hematopoiesis, peripheral blood cytopenias and an increased risk
of progression to AML. Mutations in epigenetic modifiers occur frequently in this disease and have
been shown to be sufficient to induce recapitulation of the disease in murine models. Moreover, the
distinct sensitivity of this disease to DNA methyltransferase inhibitors as well as the presence of
markedly abnormal epigenetic profiles hint to the importance that epigenetic deregulation plays in
contributing to the disease phenotype. Using genome-wide approaches we have explored the
epigenetic profiles of large cohorts of MDS and MDS/MPN overlap syndrome patients. In the meeting,
we’ll review the epigenetic programs associated with specific mutational profiles and how these may
drive biology of the disease, as well as exploring how epigenetics contribute to response to
hypomethylating agents (HMA). Finally, we will explore how the epigenetic programing contribute to
the HMA resistance phenotype in MDS.