title: Clinical features of Japanese polycythemia vera and essential thrombocythemia patients harboring CALR, JAK2V617F, JAK2Ex12del, and MPLW515L/K mutations.
abstract: The risk of complication of polycythemia vera (PV) and essential thrombocythemia (ET) by thrombosis in Japanese patients is clearly lower than in western populations, suggesting that genetic background such as race may influence the clinical features. This study aimed to clarify the relationship between genetic mutations and haplotypes and clinical features in Japanese patients with PV and ET. Clinical features were assessed prospectively among 74 PV and 303 ET patients. There were no clinical differences, including JAK2V617F allele burden, between PV patients harboring the various genetic mutations. However, CALR mutation-positive ET patients had a significantly lower WBC count, Hb value, Ht value, and neutrophil alkaline phosphatase score (NAP), and significantly more platelets, relative to JAK2V617F-positive ET patients and ET patients with no mutations. Compared to normal controls, the frequency of the JAK246/1 haplotype was significantly higher among patients with JAK2V617F, JAK2Ex12del, or MPL mutations, whereas no significant difference was found among CALR mutation-positive patients. CALR mutation-positive patients had a lower incidence of thrombosis relative to JAK2V617F-positive patients. Our findings suggest that JAK2V617F-positive ET patients and CALR mutation-positive patients have different mechanisms of occurrence and clinical features of ET, suggesting the potential need for therapy stratification in the future.
authors.affiliation: Department of Hematology, Nippon Medical School, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okabe
authors.affiliation: Department of Hematology, Nippon Medical School, Japan. Electronic address: y-hiroki@fd6.so-net.ne.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Hematology, NTT Medical Center Tokyo, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Usuki
authors.affiliation: Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Kawata
authors.affiliation: Division of Hematology and Oncology, Kyoto Prefectural University of Medicine, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroda
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Department of Hematology, Yokohama Minami Kyousai Hospital, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tajika
authors.affiliation: Department of Hematology, Yokohama Minami Kyousai Hospital, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Gomi
authors.affiliation: Department of Hematology, Kitano Hospital, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Arima
authors.affiliation: Hemato-Oncology Department, St Luke's International Hospital, Japan.
authors.forename: Sinichiro
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Hematology, Iwate Medical University, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Gastroenterology, Asahi General Hospital, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Koizumi
authors.affiliation: Department of Hematology, Tokyo Medical University, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Hematology, Nippon Medical School, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Wakita
authors.affiliation: Department of Hematology, Nippon Medical School, Japan.
authors.forename: Kunihito
authors.initials: K
authors.lastname: Arai
authors.affiliation: Department of Hematology, Nippon Medical School, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kitano
authors.affiliation: Department of Hematology, Nippon Medical School, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kosaka
authors.affiliation: Department of Hematology, Nippon Medical School, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Dan
authors.affiliation: Department of Hematology, Nippon Medical School, Japan.
authors.forename: Koiti
authors.initials: K
authors.lastname: Inokuchi
mesh_terms: D037282:Calreticulin / Q000235:genetics*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D007564:Japan; D009154:Mutation; D011087:Polycythemia Vera / Q000235:genetics*; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics*
chemical_list: D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D053614:Janus Kinase 2
keywords: CALR mutation; Essential thrombocythemia; JAK2 mutation; MPL mutation; Polycythemia vera