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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Terapia celular > DA - CIMA - Oncología - Terapia celular - Artículos de Revista >

Promoter hypomethylation of the LINE-1 retrotransposable elements activates sense/antisense transcription and marks the progression of chronic myeloid leukemia
Authors: Roman-Gomez, J. (José)
Jimenez-Velasco, A. (A.)
Aguirre, X. (Xavier)
Cervantes, F. (F.)
Sanchez, J. (Joaquín)
Garate, L. (Leire)
Barrios, M. (M.)
Castillejo, J.A. (J.A.)
Navarro, G. (Germán)
Colomer, D. (D.)
Prosper, F. (Felipe)
Heiniger, A. (A.)
Torres, A. (Antonio)
Keywords: Hypomethylation
Retrotransposons
LINE-1
Blast crisis
Issue Date: 2005
Publisher: Nature Publishing Group
Publisher version: http://dx.doi.org/10.1038/sj.onc.1208866
ISSN: 0950-9232
Citation: Roman-Gomez, J., Jimenez-Velasco, A., Agirre, X., Cervantes, F., Sanchez, J., Garate, L. et al. Promoter hypomethylation of the LINE-1 retrotransposable elements activates sense/antisense transcription and marks the progression of chronic myeloid leukemia. Oncogene 2005; 1–11
Abstract
Aberrant genome-wide hypomethylation is thought to be related to tumorigenesis by promoting genomic instability. Since DNA methylation is considered an important mechanism for the silencingof retroelements, hypomethylation in human tumors may lead to their reactivation. However, the role of DNA hypomethylation in chronic myeloid leukemia (CML) remains to be elucidated. In this study, the methylation status of the LINE-1 (L1) retrotransposon promoter was analysed in CML samples from the chronicphase (CP, n¼140) and the blast crisis (BC, n¼47). L1 hypomethylation was significantly more frequent in BC (74.5%) than in CP (38%) (Po0.0001). Furthermore, L1 hypomethylation led to activation of both ORF1 sense transcription (Po0.0001) and c-MET gene antisense transcription (Po0.0001), and was significantly associated with high levels of BCR–ABL (P¼0.02) and DNMT3b4 (P¼0.001) transcripts. Interestingly, in CP-CML, extensive L1 hypomethylation was associated with poorer prognosis in terms of cytogenetic response to interferon (P¼0.004) or imatinib (P¼0.034) and progression-free survival (P¼0.005). The above results strongly suggest that activation of both sense and antisense transcriptions by aberrant promoter hypomethylation of the L1 elements plays a role in the progression and clinical behavior of the CML.
Permanent link: http://hdl.handle.net/10171/18563
Appears in Collections:DA - CIMA - Oncología - Síndromes mieloproliferativos - Artículos de Revista
DA - CIMA - Oncología - Terapia celular - Artículos de Revista
DA - CUN - Área de Terapia Celular - Artículos de revista
DA - Medicina - Hematología - Artículos de revista

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