J Korean Med Sci.  2015 Jul;30(7):882-888. 10.3346/jkms.2015.30.7.882.

JAK2 V617F, MPL, and CALR Mutations in Korean Patients with Essential Thrombocythemia and Primary Myelofibrosis

Affiliations
  • 1Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea. yucho@amc.seoul.kr
  • 2Department of Internal Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.
  • 3Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.

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.

Keyword

CALR; JAK2 V617F; MPL; Thrombocythemia, Essential; Primary Myelofibrosis

MeSH Terms

Adult
Aged
Aged, 80 and over
Calreticulin/*genetics
Disease-Free Survival
Female
Gene Frequency
Genetic Association Studies
Humans
Janus Kinase 2/*genetics
Male
Middle Aged
Mutation/genetics
Primary Myelofibrosis/*genetics/mortality
Receptors, Thrombopoietin/*genetics
Republic of Korea
Thrombocythemia, Essential/*genetics/mortality
Young Adult
Calreticulin
Janus Kinase 2
Receptors, Thrombopoietin
Full Text Links
  • JKMS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error