2026-04-26T23:19:46Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/66562025-05-20T08:36:57Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_2173com_20.500.12105_15322col_20.500.12105_19608col_20.500.12105_19597col_20.500.12105_16977
Repisalud
author
López-Nieva, Pilar
author
Fernandez-Navarro, Pablo L
author
Vaquero-Lorenzo, Concepción
author
Villa-Morales, María
author
Graña Castro, Osvaldo
author
Cobos-Fernández, María Ángeles
author
López-Lorenzo, José Luis
author
Llamas, Pilar
author
González-Sanchez, Laura
author
Sastre, Isabel
author
Pollan-Santamaria, Marina
author
Malumbres Martinez, Marcos
author
Santos, Javier
author
Fernández-Piqueras, José
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Comunidad de Madrid (España)
funder
Fundación Ramón Areces
funder
Banco Santander
funder
Ministerio de Economía y Competitividad (España)
2018-11-21T12:30:08Z
2018-11-21T12:30:08Z
2018-04-16
BMC Cancer. 2018 Apr 16;18(1):430.
1471-2407
http://hdl.handle.net/20.500.12105/6656
29661169
10.1186/s12885-018-4304-y
1471-2407
BMC cancer
Background: Precursor T-cell lymphoblastic lymphomas (T-LBL) are rare aggressive hematological malignancies that mainly develop in children. As in other cancers, the loss of cell cycle control plays a prominent role in the pathogenesis in these malignancies that is primarily attributed to loss of CDKN2A (encoding protein p16INK4A). However, the impact of the deregulation of other genes such as CDKN1C, E2F1, and TP53 remains to be clarified. Interestingly, experiments in mouse models have proven that conditional T-cell specific deletion of Cdkn1c gene may induce a differentiation block at the DN3 to DN4 transition, and that the loss of this gene in the absence of Tp53 led to aggressive thymic lymphomas. Results: In this manuscript, we demonstrated that the simultaneous deregulation of CDKN1C, E2F1, and TP53 genes by epigenetic mechanisms and/or the deregulation of specific microRNAs, together with additional impairing of TP53 function by the expression of dominant-negative isoforms are common features in primary human T-LBLs. Conclusions: Previous experimental work in mice revealed that T-cell specific deletion of Cdkn1c accelerates lymphomagenesis in the absence of Tp53. If, as expected, the consequences of the deregulation of the CDKN1C-E2F1-TP53 axis were the same as those experimentally demonstrated in mouse models, the disruption of this axis might be useful to predict tumor aggressiveness, and to provide the basis towards the development of potential therapeutic strategiesin human T-LBL.
eng
CDKN1C-E2F1-TP53 deregulation
Deregulation of miRNAs
Promoter hypermethylation
T-cell lymphoblastic lymphoma
RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas
research article
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