, and Reprogram Thymocytes into Self-Renewing Cells

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Deciphering the initiating events in lymphoid leukemia is important for the development of new therapeutic strategies. In this manuscript, we define oncogenic reprogramming as the process through which non-self-renewing progenitors are converted into pre-leukemic stem cells with sustained self-renewal capacities. We provide strong genetic evidence that this step is rate-limiting in leukemogenesis and requires the activation of a self-renewal program by oncogenic transcription factors, as exemplified by SCL and LMO1. Furthermore, NOTCH1 is a pathway that drives cell fate in the thymus. We demonstrate that homeostatic NOTCH1 levels that are highest in specific thymocyte subsets determine their susceptibilities to oncogenic reprogramming by SCL and LMO1. Our data provide novel insight into the acquisition of self-renewal as a critical first step in lymphoid cell transformation, requiring the synergistic interaction of oncogenic transcription factors with a cellular context controlled by high physiological NOTCH1.

Vyšlo v časopise: , and Reprogram Thymocytes into Self-Renewing Cells. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004768
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004768

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