title: No evidence of cell cycle dysregulation in mantle cell lymphoma in vivo.
abstract: Mantle cell lymphoma (MCL) is characterized by the translocation t(11;14)(q13;q32) leading to an overexpression of cyclin D1, a mediator of G1-S phase transition. Thus MCL is regarded as a paradigm of lymphoma with a dysregulated cell cycle. The proliferation rate of MCL is in fact a strong predictor of outcome. We analyzed proteins that are expressed at defined cell cycle phases, such as Ki67, survivin and phosphorylated histone H3 as well as cyclin D1, p53 and p27, on the cellular level by immunofluorescence double stainings in MCL biopsy specimens. Unexpectedly, we did not detect a shortening of early phases in MCL in vivo. Despite the control of the immunoglobulin enhancer, cyclin D1 was expressed in a cell cycle-dependent manner. However, the proliferating Ki67-positive tumor cells expressed low amounts of cyclin D1. Therefore, the expression of cyclin D1 appears not to be the driving factor behind the total proliferation rate of MCL.
authors.affiliation: Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein , Campus Kiel, Kiel , Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Vogt
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Abramov
authors.forename: Karoline
authors.initials: K
authors.lastname: Koch
authors.forename: Neus
authors.initials: N
authors.lastname: Masqué-Soler
authors.forename: Monika
authors.initials: M
authors.lastname: Szczepanowski
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D020522:Lymphoma, Mantle-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C436291:CDKN1B protein, human; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D000077022:Survivin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Ki67; Mantle cell lymphoma; cell cycle; cyclin D1; immunofluorescence