title: Calreticulin mutations in Chinese with primary myelofibrosis.
abstract: We tested 357 Chinese with primary myelofibrosis for mutations in CALR, JAK2 and MPL. CALR mutations were detected in 76 subjects (21%). There were 24 (32%) type-1 (L367fs*46) and 49 (64%) type-2 (K385fs*47) mutations. Seventy-two of 168 subjects (43%) without a JAK2 or MPL mutation had a CALR mutation. Subjects with a type-2 CALR mutation had lower hemoglobin concentrations (P=0.001), lower WBC counts (P<0.001), a higher percentage of blood blasts (P=0.009), and higher conventional (P<0.001) and Chinese-adjusted Dynamic International Prognostic Scoring System (P<0.001) scores compared with subjects with JAK2 mutations. Subjects with a type-2 CALR mutation were also likely to have abnormal platelet levels (<100 × 10(9)/L, P=0.01 or >450 × 10(9)/L, P=0.042) and no splenomegaly (P=0.004). Type-2 CALR mutation or no detectable mutation was an independent high-risk factor for survival in multivariate analyses. These data suggest the ratio between type-1 and type-2 mutations is reversed in Chinese with primary myelofibrosis compared with populations of subjects with primary myelofibrosis of predominately European descent. The unfavorable prognostic impact of CALR mutations in Chinese with primary myelofibrosis is only seen in those with type-2 mutations. These data underscore the need to evaluate the prognostic impact of genetic mutations in different populations.
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Xu
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Jingya
authors.initials: J
authors.lastname: Wang
authors.affiliation: Haematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, UK.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Zefeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Ruixian
authors.initials: R
authors.lastname: Xing
authors.affiliation: Molecular Diagnostic Laboratory, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Ai
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Qin
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Peihong
authors.initials: P
authors.lastname: Zhang
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China zjxiao@hotmail.com.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D037282:Calreticulin / Q000235:genetics*; D002681:China; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D055815:Young Adult
chemical_list: D037282:Calreticulin; D053614:Janus Kinase 2