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Mechanisms of ligand-independent Notch1 activation in T-LL. In human T-LL, the Notch negative regulatory region (NRR) is often disrupted by point mutations or less frequently by chromosomal translocations, whereas in murine T-LL the NRR is most commonly disrupted are 5’ deletions (most RAG mediated) followed by retroviral insertions. Examples of dissociative (red), destabilizing (blue), and insertional (green) Notch1 NRR mutations found in human T-LL are listed.
