title: Alterations in TP53, cyclin D2, c-Myc, p21WAF1/CIP1 and p27KIP1 expression associated with progression in B-CLL.
abstract: B-cell chronic lymphocytic leukaemia (B-CLL) originates from B lymphocytes that may differ in the activation level, maturation state or cellular subgroups in peripheral blood. Tumour progression in CLL B cells seems to result in gradual accumulation of the clone of resting B lymphocytes in the early phases (G0/G1) of the cell cycle. The G1 phase is impaired in B-CLL. We investigated the gene expression of five key cell cycle regulators: TP 53, c-Myc, cyclin D2, p21WAF1/CIP1 and p27KIP1, which primarily regulate the G1 phase of the cell cycle, or S-phase entry and ultimately control the proliferation and cell growth as well as their role in B-CLL progression. The study was conducted in peripheral blood CLL lymphocytes of 40 previously untreated patients. Statistical analysis of correlations of TP53, cyclin D2, c-Myc, p21WAF1/CIP1 and p27KIP1 expressions in B-CLL patients with different Rai stages demonstrated that the progression of disease was accompanied by increases in p53, cyclin D2 and c-Myc mRNA expression. The expression of p27KIP1 was nearly statistically significant whereas that of p21 WAF1/CIP1 showed no such correlation. Moreover, high expression levels of TP53 and c-Myc genes were found to be closely associated with more aggressive forms of the disease requiring earlier therapy.
authors.affiliation: Department of Clinical Genetics, Medical University of Lublin, Lublin, Poland. hagenetyka@wp.pl
authors.forename: Antosz
authors.initials: A
authors.lastname: Halina
authors.forename: Paterski
authors.initials: P
authors.lastname: Artur
authors.forename: Marzec-Kotarska
authors.initials: MK
authors.lastname: Barbara
authors.forename: Sajewicz
authors.initials: S
authors.lastname: Joanna
authors.forename: Dmoszyńska
authors.initials: D
authors.lastname: Anna
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056742:Cyclin D2 / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27