Abstract SY35-03: Gene expression and epigenetic programs in leukemia stem cell development

Abstract

Abstract Acute myelogenous leukemia stem cells (LSC) are the subset of leukemia cells capable of extensive self-renewal and maintenance of leukemia. We are interested in the mechanisms of leukemia development as they relate to activation and maintenance of gene expression programs by epigenetic pathways responsible for deregulated self-renewal in leukemia. We have demonstrated that oncogenic fusion proteins can activate a self-renewal associated gene expression program when expressed in myeloid progenitor cells that normally have limited self-renewal capabilities. Detailed characterization of LSC from multiple different mouse leukemias has shown that LSC are most similar to differentiating myeloid cells that express a limited hematopoietic stem cell (HSC) associated signature. Detailed analysis of the gene expression data from normal HSC and progenitors as compared to LSC identified the Wnt/β-catenin pathway as potentially important for acute myeloid leukemia LSC, and we have subsequently validated this pathway as critical using conditional mouse models. We are continuing to assess the gene expression programs subverted during the transition from normal HSC and progenitor cells to LSC and are comparing these data to genome wide epigenomic analyses to determine which specific epigenetic programs are required for leukemia stem cell maintenance. Identification of epigenetic pathways required to maintain leukemia self-renewal should provide new targets for novel therapeutic approaches. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY35-03. doi:1538-7445.AM2012-SY35-03