title: Distinct molecular genetics of chronic lymphocytic leukemia in Taiwan: clinical and pathogenetic implications.
abstract: Differences in chronic lymphocytic leukemia between the Asian and the Western population are widely known. To further clarify these ethnic differences, we profiled the molecular genetics in a cohort of 83 newly diagnosed patients from Taiwan. In detail, we assessed: (i) the usage and the mutational status of the clonotypic immunoglobulin heavy-chain variable region (IgHV) genes, (ii) the presence of VH CDR3 stereotypes, and (iii)TP53, NOTCH1, SF3B1, BIRC3, andMYD88mutations. TheIgHVgene repertoire was biased and distinct from that observed in the West with the most commonIgHVgenes beingIgHV3-23, IgHV3-7, andIgHV3-48In terms ofIgHVgene mutational status, 63.8% of patients carried mutated rearrangements, whereas 22.4% of patients were assigned to stereotyped subsets (6.9% to major subsets and 15.5% to minor ones). The frequencies ofNOTCH1,SF3B1, BIRC3andMYD88mutations were 9.6%, 7.2%, 1.2%, and 2.4%, respectively; however, the frequency ofTP53mutations was significantly higher (20.5%). Patients withTP53mutations or del(17p),SF3B1mutations and unmutatedIgHVhad a worse outcome compared to the other patients. In conclusion, the differences observed inIgHVproperties suggest different pathogenetic factors implicated in the development of chronic lymphocytic leukemia, while the high frequency ofTP53mutations could in part explain the dismal outcome of these patients in Taiwan.
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Shang-Ju
authors.initials: SJ
authors.lastname: Wu
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Tai-Cheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan.
authors.forename: Chien-Ting
authors.initials: CT
authors.lastname: Lin
authors.affiliation: Strategic Research Program on CLL and B-cell Neoplasia Unit, Division of Experimental Oncology, Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Andreas
authors.initials: A
authors.lastname: Agathangelidis
authors.affiliation: Department of Clinical Laboratory Science and Medical Technology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Liang-In
authors.initials: LI
authors.lastname: Lin
authors.affiliation: Graduate Institution of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yuan-Yeh
authors.initials: YY
authors.lastname: Kuo
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan hftien@ntu.edu.tw ghia.paolo@hsr.it.
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
authors.affiliation: Strategic Research Program on CLL and B-cell Neoplasia Unit, Division of Experimental Oncology, Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan, Italy hftien@ntu.edu.tw ghia.paolo@hsr.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
mesh_terms: D044466:Asian People / Q000235:genetics; D022801:Complementarity Determining Regions / Q000235:genetics*; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000208:ethnology* / Q000235:genetics*; D009154:Mutation; D059645:Mutation Rate; D011379:Prognosis; D013624:Taiwan / Q000208:ethnology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D022801:Complementarity Determining Regions; D016159:Tumor Suppressor Protein p53