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Albert Einstein College of Medicine
Identification of Functionally Critical Transcriptional Target Genes in Stem Cells in AML & MDS
Despite the use polychemotherapies which reduce the tumor burden, relapse continues to be the most common cause of death in myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML). Recent evidence demonstrates that rare so-called leukemia stem cells (LSC) give rise to functionally heterogeneous bulk tumor cells with limited life-span. To identify functionally critical LSC pathways, fundamentally novel experimental approaches other than the examination of bulk tumor cells need to be established. The Steidl lab uses a specialized cell sorting method to isolate precisely defined stem cells based on marker molecules on the cell surface, and then examines these fractionated cells by a genome-wide analysis method of gene activity. Genes can be identified that are differentially active in stem cells from patients with MDS and AML in comparison to normal stem cells, and then be tested for functional relevance. The study supported by the Gabrielle’s Angel Foundation will enhance the knowledge of disease-causing mechanisms at the stem cell level in MDS and AML, and identify molecular targets for LSC-directed therapeutic approaches.