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Combined PER2 and CRY1 expression predicts outcome in chronic lymphocytic leukemia.
Eisele, Lewin; Prinz, Robert; Klein-Hitpass, Ludger; Nückel, Holger; Lowinski, Kerstin; Thomale, Jürgen; Moeller, Lars C; Dührsen, Ulrich; Dürig, Jan.
Afiliação
  • Eisele L; Department of Hematology, University Hospital, Hufelandstrasse 55, Essen, Germany. lewin.eisele@uni-due.de
Eur J Haematol ; 83(4): 320-7, 2009 Oct.
Article em En | MEDLINE | ID: mdl-19500131
ABSTRACT
The objective of this study was to confirm previous results regarding the differential expression and prognostic significance of the circadian gene CRY1 in chronic lymphocytic leukemia (CLL) patients and its relationship with the expression of other circadian genes and well-established prognostic markers. We also aimed to investigate whether the peripheral circadian machinery may be deregulated in CLL cells. The expression of CRY1, PER1, and PER2 was determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in 116 CLL patients. The expression at sequential time points over a 24-h period was measured in six CLL patients and six normal donors. We confirmed the differential expression of CRY1 in ZAP-70(+)/CD38(+) and ZAP-70(-)/CD38(-) CLL samples. Subgroups formed according to CRY1 expression levels differed significantly in time to treatment. This difference was even more pronounced for subgroups stratified by a CRY1 PER2 expression ratio and the ratio was an independent prognostic marker in a multivariate model. Furthermore, our data indicate disturbances in the periodic expression of circadian genes in CLL cells. Because of their role in the expression of cell cycle-related and DNA-damage response genes, we suggest that the deregulated expression of circadian genes may be linked to the molecular pathogenesis of CLL.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Proteínas Nucleares / Leucemia Linfocítica Crônica de Células B / Regulação Neoplásica da Expressão Gênica / Valor Preditivo dos Testes / Flavoproteínas Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2009 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Proteínas Nucleares / Leucemia Linfocítica Crônica de Células B / Regulação Neoplásica da Expressão Gênica / Valor Preditivo dos Testes / Flavoproteínas Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2009 Tipo de documento: Article