Journal article
Re-activation of mitochondrial apoptosis inhibits T-cell lymphoma survival and treatment resistance
S Spinner, G Crispatzu, JH Yi, E Munkhbaatar, P Mayer, U Höckendorf, N Müller, Z Li, T Schader, H Bendz, S Hartmann, M Yabal, K Pechloff, M Heikenwalder, GL Kelly, A Strasser, C Peschel, ML Hansmann, J Ruland, U Keller Show all
Leukemia | Published : 2016
DOI: 10.1038/leu.2016.49
Abstract
T lymphocyte non-Hodgkin's lymphoma (T-NHL) represents an aggressive and largely therapy-resistant subtype of lymphoid malignancies. As deregulated apoptosis is a frequent hallmark of lymphomagenesis, we analyzed gene expression profiles and protein levels of primary human T-NHL samples for various apoptotic regulators. We identified the apoptotic regulator MCL-1 as the only pro-survival BCL-2 family member to be highly expressed throughout all human T-NHL subtypes. Functional validation of pro-survival protein members of the BCL-2 family in two independent T-NHL mouse models identified that the partial loss of Mcl-1 significantly delayed T-NHL development in vivo. Moreover, the inducible re..
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Awarded by DFG
Awarded by Max Eder-Program grants from the Deutsche Krebshilfe
Awarded by Human Frontiers Science Program grant
Awarded by German Jose Carreras Leukemia Foundation grant
Awarded by Else Korner Fresenius-Stiftung
Funding Acknowledgements
We thank Stephanie Rott and Smaro Beskeli for excellent technical assistance. PJJ was supported by the DFG Research Unit FOR2036, Max Eder-Program grants from the Deutsche Krebshilfe (program nos. 109310 and 111738), a Human Frontiers Science Program grant (program no. RGY0073/ 2012), the German Jose Carreras Leukemia Foundation grant (DJCLS R 12/22) and a grant from the Else Korner Fresenius-Stiftung (2014-A185). MH (Cologne) was supported by the DFG Research Unit 'CONTROL-T' FOR1961 (HE3553/4-1) and Max Eder-Program grants from the Deutsche Krebshilfe (program no. 108029). SN was supported by the DFG Research Unit 'CONTROL-T' FOR1961 (NE1438/4-1). GLK and AS were supported by fellowships and grants from the NHMRC and the Redstone Foundation Trust; AS by LLS and Cancer Council of Victoria. MH (Munich) was supported by an ERC starting grant (LiverCancerMechanisms), the Stiftung Experimentelle Biomedizin and the Helmholtz-Zentrum.