title: JAK2 V617F, MPL, and CALR Mutations in Korean Patients with Essential Thrombocythemia and Primary Myelofibrosis.
abstract: Mutations in the calreticulin gene, CALR, have recently been discovered in subsets of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). We investigated Korean patients with ET and PMF to determine the prevalence, and clinical and laboratory correlations of CALR/JAK2/MPL mutations. Among 84 ET patients, CALR mutations were detected in 23 (27.4%) and were associated with higher platelet counts (P=0.006) and lower leukocyte counts (P=0.035) than the JAK2 V617F mutation. Among 50 PMF patients, CALR mutations were detected in 11 (22.0%) and were also associated with higher platelet counts (P=0.035) and trended to a lower rate of cytogenetic abnormalities (P=0.059) than the JAK2 V617F mutation. By multivariate analysis, triple-negative status was associated with shorter overall survival (HR, 7.0; 95% CI, 1.6-31.1, P=0.01) and leukemia-free survival (HR, 6.3; 95% CI, 1.8-22.0, P=0.004) in patients with PMF. The type 1 mutation was the most common (61.1%) type among all patients with CALR mutations, and tended toward statistical predominance in PMF patients. All 3 mutations were mutually exclusive and were never detected in patients with other myeloid neoplasms showing thrombocytosis. CALR mutations characterize a distinct group of Korean ET and PMF patients. Triple-negative PMF patients in particular have an unfavorable prognosis, which supports the idea that triple-negative PMF is a molecularly high-risk disease.
authors.affiliation: Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Young-Uk
authors.initials: YU
authors.lastname: Cho
authors.affiliation: Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Bae
authors.affiliation: Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Seongsoo
authors.initials: S
authors.lastname: Jang
authors.affiliation: Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Eul-Ju
authors.initials: EJ
authors.lastname: Seo
authors.affiliation: Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Hyun-Sook
authors.initials: HS
authors.lastname: Chi
authors.affiliation: Department of Internal Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Yunsuk
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Park
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jong-Keuk
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Chan-Jeoung
authors.initials: CJ
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D037282:Calreticulin / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D055728:Primary Myelofibrosis / Q000235:genetics* / Q000401:mortality; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D056910:Republic of Korea; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000401:mortality; D055815:Young Adult
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: CALR; JAK2 V617F; MPL; Primary Myelofibrosis; Thrombocythemia, Essential