title: Frequencies of SF3B1, NOTCH1, MYD88, BIRC3 and IGHV mutations and TP53 disruptions in Chinese with chronic lymphocytic leukemia: disparities with Europeans.
abstract: We studied 307 consecutive Chinese with chronic lymphocytic leukemia (CLL) in diverse disease-stages before and after diverse therapies for mutations in several CLL-related genes. Mutation frequencies were SF3B1, 5%, NOTCH1, 8%, MYD88, 8%, BIRC3, 2%, TP53, 15% and IGHV, 60%. Several of these frequencies differ from those reported in persons of predominately European descent with CLL. Biological and clinical associations were detected including SF3B1 and NOTCH1 mutations with un-mutated IGHV, MYD88 mutations with mutated IGHV, SF3B1 mutations with fludarabine-resistant CLL and NOTCH1 mutation with advanced Binet disease stage and with +12. The NOTCH1 correlation with briefer survival was confirmed in multivariate analyses but the SF3B1 correlation was confounded by concurrent mutations in TP53 and germline IGHV. We show differences in incidence and prognostic impact of mutations in Chinese and CLL compared with persons of predominately European descent with CLL. These data may give insights into the etiology and biology of CLL and suggests different risk stratification models may be needed for different CLL populations.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Hematology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Yao-Yu
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D014408:Biomarkers, Tumor / Q000235:genetics*; D002681:China / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000235:genetics; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D054624:Health Status Disparities; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1 / Q000235:genetics; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051034:Inhibitor of Apoptosis Proteins; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C497761:NOTCH1 protein, human; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases
keywords: MYD88; NOTCH1; SF3B1; chronic lymphocytic leukemia; mutation