RT Journal Article
T1 S194-P-FADD as a marker of aggressiveness and poor prognosis in human T-cell lymphoblastic lymphoma
A1 Marín-Rubio, José L.
A1 Pérez Gómez, Eduardo
A1 Fernández-Piqueras, José
A1 Villa-Morales, María
AB T-cell lymphoblastic lymphoma is a haematological disease with an urgent need for reliable prognostic biomarkers that allow therapeutic stratification and dose adjustment. The scarcity of human samples is responsible for the delayed progress in the study and the clinical management of this disease, especially compared with T-cell acute lymphoblastic leukaemia, its leukemic counterpart. In the present work, we have determined by immunohistochemistry that S194-P-FADD protein is significantly reduced in a cohort of 22 samples from human T-cell lymphoblastic lymphoma. Notably, the extent of such reduction varies significantly among samples and has revealed determinant for the outcome of the tumour. We demonstrate that Fas-associated protein with death domain (FADD) phosphorylation status affects protein stability, subcellular localization and non-apoptotic functions, specifically cell proliferation. Phosphorylated FADD would be more stable and preferentially localized to the cell nucleus; there, it would favour cell proliferation. We show that patients with higher levels of S194-P-FADD exhibit more proliferative tumours and that they present worse clinical characteristics and a significant enrichment to an oncogenic signature. This supports that FADD phosphorylation may serve as a predictor for T-cell lymphoblastic lymphoma aggressiveness and clinical status. In summary, we propose FADD phosphorylation as a new biomarker with prognostic value in T-cell lymphoblastic lymphoma.
PB Oxford University Press
SN 1460-2180
YR 2019
FD 2019-02-26
LK https://hdl.handle.net/20.500.14352/12356
UL https://hdl.handle.net/20.500.14352/12356
LA eng
NO Ministerio de Economía y Competitividad (MINECO)/FEDER
NO Ministerio de Economía y Competitividad (MINECO)
NO Comunidad de Madrid
NO Instituto de Salud Carlos III  (ISCIII)
NO Asociación Española Contra el Cáncer (AECC)
NO Ministerio de Educación, Cultura y Deporte (MECD)
NO Fundación Ramón Areces
NO Banco Santander
DS Docta Complutense
RD 6 abr 2025