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mRNA overexpression of the hypoxia inducible factor 1 alpha subunit gene (HIF1A): An independent predictor of poor overall survival in chronic lymphocytic leukemia.
Kontos, Christos K; Papageorgiou, Sotirios G; Diamantopoulos, Marios A; Scorilas, Andreas; Bazani, Efthimia; Vasilatou, Diamantina; Gkontopoulos, Konstantinos; Glezou, Eirini; Stavroulaki, Georgia; Dimitriadis, George; Pappa, Vasiliki.
Afiliación
  • Kontos CK; Second Department of Internal Medicine and Research Unit, University General Hospital "Attikon", 1 Rimini St., Haidari, 12462 Athens, Greece; Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Panepistimiopolis, 15701 Athens, Greece.
  • Papageorgiou SG; Second Department of Internal Medicine and Research Unit, University General Hospital "Attikon", 1 Rimini St., Haidari, 12462 Athens, Greece.
  • Diamantopoulos MA; Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Panepistimiopolis, 15701 Athens, Greece.
  • Scorilas A; Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Panepistimiopolis, 15701 Athens, Greece.
  • Bazani E; Second Department of Internal Medicine and Research Unit, University General Hospital "Attikon", 1 Rimini St., Haidari, 12462 Athens, Greece.
  • Vasilatou D; Second Department of Internal Medicine and Research Unit, University General Hospital "Attikon", 1 Rimini St., Haidari, 12462 Athens, Greece.
  • Gkontopoulos K; Second Department of Internal Medicine and Research Unit, University General Hospital "Attikon", 1 Rimini St., Haidari, 12462 Athens, Greece.
  • Glezou E; Second Department of Internal Medicine and Research Unit, University General Hospital "Attikon", 1 Rimini St., Haidari, 12462 Athens, Greece.
  • Stavroulaki G; Second Department of Internal Medicine and Research Unit, University General Hospital "Attikon", 1 Rimini St., Haidari, 12462 Athens, Greece.
  • Dimitriadis G; Second Department of Internal Medicine and Research Unit, University General Hospital "Attikon", 1 Rimini St., Haidari, 12462 Athens, Greece.
  • Pappa V; Second Department of Internal Medicine and Research Unit, University General Hospital "Attikon", 1 Rimini St., Haidari, 12462 Athens, Greece. Electronic address: vas_pappa@yahoo.com.
Leuk Res ; 53: 65-73, 2017 02.
Article en En | MEDLINE | ID: mdl-28038356
The hypoxia inducible factor 1 (HIF1) is a heterodimeric transcription factor that ultimately regulates cellular responses to changes in oxygen tension. In this study, we examined the potential diagnostic and prognostic potential of the mRNA expression of HIF1 regulatory α-subunit (HIF1A) in chronic lymphocytic leukemia (CLL). For this purpose, total RNA was isolated from peripheral blood mononuclear cells collected from 88 CLL patients and 33 non-leukemic blood donors, and poly(A)-RNA was reversely transcribed. HIF1A mRNA levels were quantified using real-time PCR. Kaplan-Meier survival analysis showed that high HIF1A mRNA expression predicts inferior overall survival for CLL patients (p=0.001). Bootstrap univariate Cox regression analysis confirmed that HIF1A mRNA overexpression is a significant unfavorable prognosticator in CLL (hazard ratio=3.75, bias-corrected and accelerated 95% confidence interval=1.43-24.36, bootstrap p<0.001), independent of other established prognostic factors, including CD38 expression, the mutational status of the immunoglobulin heavy chain variable region (IGHV), and the clinical stage (Binet or Rai stage) or risk group (p<0.001 in all cases). Interestingly, HIF1A mRNA positivity retains its unfavorable prognostic value in distinct subgroups of patients, stratified according to established prognostic factors. Thus, HIF1A mRNA overexpression can be regarded as a promising, independent molecular biomarker of unfavorable prognosis in CLL.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Subunidad alfa del Factor 1 Inducible por Hipoxia Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Leuk Res Año: 2017 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Subunidad alfa del Factor 1 Inducible por Hipoxia Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Leuk Res Año: 2017 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Reino Unido