MNT suppresses T cell apoptosis via BIM and is vital for MYC-driven T lymphomagenesis

Abstract The importance of c-MYC in regulating normal lymphopoiesis and promoting lymphomagenesis is well-established, but far less appreciated is the vital supporting role of MYC’s relative MNT. We show here that, during normal T cell development, MNT loss enhances apoptosis and establish the mechanism as elevated expression of the pro-apoptotic BH3-only protein BIM. Using a MYC transgenic mouse model, we also show that MNT loss reduces the pool of premalignant MYC-driven T cells and totally abrogates thymic T lymphomagenesis. Taken together with our recent demonstration that MNT is vital for the survival of MYC-driven premalignant and malignant B lymphoid cells, these results suggest that MNT represents an important new drug target for both T and B lymphoid malignancies.