title: No increase of JAK2 46/1 haplotype frequency in essential thrombocythemia with CALR mutations: Functional effect of the haplotype limited to allele with JAK2V617F mutation but not CALR mutation.
abstract: The true frequency of the JAK2 46/1 haplotype in patients of myeloproliferative neoplasms (MPN) with CALR mutations was unknown. Totally 187 MPN cases with diagnosis of polycythemia vera (PV) and essential thrombocythemia (ET) were recruited. The frequency of 46/1 haplotype was significantly higher in JAK2V617F-positive PV (51%, p < 0.001) and ET (41%, p = 0.005) compared to normal controls. The exact location of JAK2V617F mutation was located at the cis-46/1 haplotype in 86.4% (32/37) PV patients and 87.5% (28/32) ET patients, respectively. Among the 51 patients of ET without JAK2V617F mutation, 38 (75%) patients harbored CALR mutations and 3 patients had MPL mutation. The frequency of 46/1 haplotype in the 38 ET patients with CALR mutations was 27%, which is not significantly different from that of normal control (p value = 0.879). Compared to non-46/1 haplotype, the presence of 46/1 haplotype had a trend to have higher white blood cell count in JAK2V617F-mutated PV and ET patients but not in CALR-mutated ET. We conclude that the 46/1 haplotype could have functioning effect but only in the context of JAK2V617F mutation.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, Taipei, Taiwan. Electronic address: gau.jyhpyng@gmail.com.
authors.forename: Jyh-Pyng
authors.initials: JP
authors.lastname: Gau
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan. Electronic address: ccchen1968@gmail.com.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
authors.affiliation: National Yang-Ming University School of Medicine, Taipei, Taiwan; Lotung Poh-Ai Hospital, Yilan, Taiwan.
authors.forename: Yi-Sheng
authors.initials: YS
authors.lastname: Chou
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, Taipei, Taiwan; Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Yuan-Bin
authors.initials: YB
authors.lastname: Yu
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Liang-Tsai
authors.initials: LT
authors.lastname: Hsiao
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, Taipei, Taiwan; Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Jin-Hwang
authors.initials: JH
authors.lastname: Liu
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Tzeon-Jye
authors.initials: TJ
authors.lastname: Chiou
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Po-Min
authors.initials: PM
authors.lastname: Chen
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Cheng-Hwai
authors.initials: CH
authors.lastname: Tzeng
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D037282:Calreticulin / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D011087:Polycythemia Vera / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000473:pathology
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: CALR mutation; Genetic polymorphism; Haplotype; JAK2 mutation; Myeloproliferative neoplasms