Promoter hypomethylation of the LINE-1 retrotransposable elements activates sense/antisense transcription and marks the progression of chronic myeloid leukemia
Roman-Gomez J, Jimenez-Velasco A, Agirre X, Cervantes F, Sanchez J, Garate L, Barrios M, Castillejo JA, Navarro G, Colomer D, Prosper F, Heiniger A, Torres A.
Hematology Department, Reina Sofia Hospital, Avda. Menendez Pidal s/n. 14004, Cordoba, Spain
Data: 3/Nov/2005Área de Terapia Celular [ES]
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 silencing of 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 chronic-phase (CP, n=140) and the blast crisis (BC, n=47). L1 hypomethylation was significantly more frequent in BC (74.5%) than in CP (38%) (P<0.0001). Furthermore, L1 hypomethylation led to activation of both ORF1 sense transcription (P<0.0001) and c-MET gene antisense transcription (P<0.0001), and was significantly associated with high levels of BCR-ABL (P=0.02) and DNMT3b4 (P=0.001) transcripts. Interestingly, in CP-CML, extensive L1 hypomethylation was associated with poorer prognosis in terms of cytogenetic response to interferon (P=0.004) or imatinib (P=0.034) and progression-free survival (P=0.005).
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.
CITAÇÃO DO ARTIGO Oncogene. 2005 Nov 3;24(48):7213-23
A Clínica é o hospital privado com maiores recursos tecnológicos de Espanha, tudo num único centro.
Os profissionais da Clínica realizam um trabalho contínuo de investigação e formação, sempre em benefício do paciente.
Conheça porque é que somos diferentes em relação a outros centros sanitários. Qualidade, rapidez, comodidade e resultados.