title: Evaluation of Caspase-9b and PP2Acα2 as potential biomarkers for chronic lymphocytic leukemia.
abstract: BACKGROUND
  Disruption of alternative splicing in apoptotic factors has been associated to chronic lymphocytic leukemia among other cancers and hematological malignancies. The proapoptotic proteins Caspase-9 and PP2Acα are functionally related in a direct interaction, which constitutes a promising target for cancer therapy. Both proteins present aberrant mRNA splicing variants that are antiapoptotic (Caspase-9b) and catalytically inactive (PP2Acα2), respectively.
  
  
  RESULTS
  In this work we have analyzed the relative abundance of the aberrant spliced forms Caspase-9b and PP2Acα2 in several cell lines and chronic lymphocytic leukemia patients and correlated it with several parameters of the disease. Despite 40 % of the patients presented Caspase-9b dysregulation, there was no direct association between alterations in Caspase-9b relative abundance and the parameters analyzed in medical records. More importantly, PP2Acα2 dysregulation was observed in 88 % of CLL patients and was related with advanced stages of the malignancy.
  
  
  CONCLUSIONS
  Caspase-9b dysregulation seemed to be associated with the disease, although the differences between healthy donors and CLL patients were not statistically significant. However, PP2Acα2 dysregulation was significantly different between healthy donors and CLL patients and correlated with Binet B and C stages; therefore, we propose the use of PP2Acα2 dysregulation as a potential biomarker for advanced stages of chronic lymphocytic leukemia.
authors.affiliation: Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC), c/ Jaime Roig 11, 46010 Valencia, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Domínguez-Berrocal
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1135, 83, Université Pierre et Marie Curie, 91 bd de l'Hôpital, 75013 Paris, France.
authors.forename: Xiguang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Saint Louis, 1 avenue Claude Vellefaux, 75010 Paris, France.
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Zini
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1135, 83, Université Pierre et Marie Curie, 91 bd de l'Hôpital, 75013 Paris, France.
authors.forename: Jesús
authors.initials: J
authors.lastname: Fominaya
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1135, 83, Université Pierre et Marie Curie, 91 bd de l'Hôpital, 75013 Paris, France.
authors.forename: Angelita
authors.initials: A
authors.lastname: Rebollo
authors.affiliation: Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC), c/ Jaime Roig 11, 46010 Valencia, Spain.
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Bravo
keywords: Alternative splicing; Biomarker; Caspase-9; Caspase-9b; Chronic lymphocytic leukemia; PP2Acα; PP2Acα2