title: High expression of PI3K core complex genes is associated with poor prognosis in chronic lymphocytic leukemia.
abstract: Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in the Western world. Autophagy is a highly conserved process in eukaryotic cells. In CLL autophagy is involved in mediating the effect of chemotherapy but the role of autophagy in CLL pathogenesis remains unknown. In the present study, we used real-time RT-PCR to analyze expression of the PIK3C3, PIK3R4, and BECN1 genes. These genes encode the components of the PI3K core complex, which is central to initiation of autophagy. A consecutive series of 149 well-characterized CLL cases from Region of Southern Denmark were included in the study. All three genes were observed to be independent markers of prognosis in CLL with high expression being associated with more aggressive disease. With this clear association with outcome in CLL, these genes thereby represent promising candidates for future functional studies on the role of autophagy in CLL, and they may further represent targets of treatment.
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Kristensen
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kristensen
authors.affiliation: Department of Hematology, Odense University Hospital, Odense, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Abildgaard
authors.affiliation: Department of Genetics, Odense University Hospital, Odense, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Thomassen
authors.affiliation: Department of Hematology, Haderslev Hospital, Haderslev, Denmark.
authors.forename: Mikael
authors.initials: M
authors.lastname: Frederiksen
authors.affiliation: Department of Hematology, Hospital of Southwestern Jutland, Esbjerg, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Mourits-Andersen
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark. Electronic address: Michael.boe.moeller@rsyd.dk.
authors.forename: Michael Boe
authors.initials: MB
authors.lastname: Møller
mesh_terms: D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D000071186:Beclin-1; D018572:Disease-Free Survival; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000401:mortality; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D008875:Middle Aged; D015996:Survival Rate; D058571:Vacuolar Sorting Protein VPS15 / Q000096:biosynthesis*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; C546851:PIK3R4 protein, human; D058571:Vacuolar Sorting Protein VPS15
keywords: Autophagy; BECN1; Chronic lymphocytic leukemia; PIK3C3; PIK3R4; Prognosis