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Proposed model for targeting the AF9-DOT1L interaction. Disrupting the AF9-DOT1L PPI downregulates H3K79me and HoxA9 and Meis1 expression leading to cell differentiation and cell death. In contrast, in non-leukemic bone marrow (BM), the AF9-DOT1L interaction is dispensable wherein hematopoietic stem and progenitor cells are sustained.
