Hypermethylation of 5'-region of the human calcitonin gene in leukemias: structural features and diagnostic significance.

Marinitch, D V; Vorobyev, I A; Holmes, J A; Zakharchenko, N S; Dyachenko, O V; Buryanov, Ya I; Shevchuk, T V

Marinitch, D V; Vorobyev, I A; Holmes, J A; Zakharchenko, N S; Dyachenko, O V; Buryanov, Ya I; Shevchuk, T V.

Afiliación

Marinitch DV; Research Institute of Hematology and Blood Transfusion, Minsk 223059, Belarus'. rihbtgapa@gtp.by

Biochemistry (Mosc) ; 69(3): 340-9, 2004 Mar.

Article en En | MEDLINE | ID: mdl-15061703

RESUMEN

Methylation of the 5'-region of the calcitonin gene was investigated in bone marrow and peripheral blood cells of 27 healthy volunteers and 25 leukemic patients. In all patients suffering from various forms of myeloid and lymphoid leukemia, hypermethylation of CpG sequences was observed in this region of the calcitonin gene. Cytosine hypermethylation in the CpG sequence did not involve cytosines of adjacent CpNpG sequences (where N is any nucleoside). The 5'-region of the calcitonin gene lacked CpNpG methylation both in healthy controls and in leukemic patients; this apparently represents specific "non-alternative" type of CpG methylation in the extended DNA sequence. Methylation of the calcitonin gene was monitored in 18 leukemic patients during malignant progression and medical treatment. Hypermethylation of the calcitonin gene was not observed on long-term clinical hematological remission. In ten patients characterized by unstable (or incomplete) remission hypermethylation of the calcitonin gene persisted through the whole period of observation. In relapses, hypermethylation of the calcitonin gene appeared again and in six patients, this "molecular relapse" being registered 1-8 months before onset of clinical and laboratory signs of disease progression. The leukemia-specific hypermethylation of CpG sequences of the 5'-region of the calcitonin gene is a promising prognostic and diagnostic marker of leukemias and might be useful for monitoring of this disease.

Asunto(s)

Región de Flanqueo 5'/genética; Biomarcadores de Tumor/genética; Calcitonina/genética; Metilación de ADN; Leucemia/genética; Islas de CpG/genética; Femenino; Humanos; Leucemia/diagnóstico; Leucemia/terapia; Masculino; Neoplasia Residual/genética; Valor Predictivo de las Pruebas; Recurrencia; Inducción de Remisión

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calcitonina / Leucemia / Biomarcadores de Tumor / Metilación de ADN / Región de Flanqueo 5' Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Biochemistry (Mosc) Año: 2004 Tipo del documento: Article Pais de publicación: Estados Unidos

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