During my doctoral studies, I discovered that an ETP-like subtype of T-ALL is dependent on MYCN. Building upon preliminary results that indicate an important role of H3K4 methylation in controlling MYCN gene expression in these leukemias, my present research seeks to identify the key epigenetic modifiers responsible for establishing and/or maintaining H3K4 methylation in the context of T-ALL development. Ultimately, this investigation may unveil novel pharmacological targets for combating T-ALL.


Pathogenetic mechanisms in T-ALL

Using our recently developed cord blood transduction approach, we are able to generate synthetic T-ALL by de novo transformation of normal human hematopoietic progenitors with activated NOTCH1 in combination with accessory oncogenes (M. Kusakabe et al, Nature Communications, 2019). This model generates polyclonal expansions of pre-leukemia cells in vitro within 3-4 weeks, which then produce clonal T-ALL disease within 3 months after injection into immunodeficient mice. Using this model, we are actively exploring the following areas:

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