title: Role of ZNF224 in cell growth and chemoresistance of chronic lymphocitic leukemia.
abstract: Chronic lymphocytic leukaemia (CLL) is associated with apoptosis resistance and defective control of cell growth. Our study describes for the first time a critical role in CLL for the KRAB-zinc finger protein ZNF224. High ZNF224 transcript levels were detected in CLL patients with respect to control cells. Moreover, ZNF224 expression was significantly lowered after conventional chemotherapy treatment in a subset of CLL patients. By in vitro experiments we confirmed that ZNF224 expression is suppressed by fludarabine and demonstrated that ZNF224 is involved in apoptosis resistance in CLL cells. Moreover, we showed that ZNF224 positively modulates cyclin D3 gene expression. Consistently, we observed that alteration of ZNF224 expression leads to defects in cell cycle control. All together, our results strongly suggest that in CLL cells high expression level of ZNF224 can lead to inappropriate cell growth and apoptosis resistance, thus contributing to CLL progression. Targeting ZNF224 could thus improve CLL response to therapy.
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini 5 80131, Naples, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Busiello
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini 5 80131, Naples, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Ciano
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini 5 80131, Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Romano
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini 5 80131, Naples, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Sodaro
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini 5 80131, Naples, Italy.
authors.forename: Olgavalentina
authors.initials: O
authors.lastname: Garofalo
authors.affiliation: Department of Public Health, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Bruzzese
authors.affiliation: Division of Hematology, Department of Clinical and Experimental Medicine, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.
authors.forename: Luigia
authors.initials: L
authors.lastname: Simeone
authors.affiliation: Division of Hematology, Department of Clinical and Experimental Medicine, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Chiurazzi
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini 5 80131, Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Fiammetta Romano
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini 5 80131, Naples, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Costanzo
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini 5 80131, Naples, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cesaro
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D056743:Cyclin D3 / Q000096:biosynthesis / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: C534696:CCND3 protein, human; D056743:Cyclin D3; D012097:Repressor Proteins; C470003:ZNF224 protein, human; D014740:Vidarabine; C024352:fludarabine