title: Coexistence of JAK2 and CALR mutations and their clinical implications in patients with essential thrombocythemia.
abstract: Janus kinase 2 (JAK2) and calreticulin (CALR) constitute the two most frequent mutations in essential thrombocythemia (ET), and both are reported to be mutually exclusive. Hence, we examined a cohort of 123 myeloproliferative neoplasm (MPN) patients without BCR-ABL1 rearrangement and additional ET patients (n=96) for coexistence of JAK2 and CALR mutations. The frequency of CALR mutations was 20.3% in 123 MPN patients; 31.1% in ET (n=74), 25% in primary myelofibrosis (n=4) and 2.2% in polycythemia vera (n=45). JAK2 and CALR mutations coexisted in 7 (4.2%) of 167 ET patients. Clinical characteristics, progression-free survival (PFS), and elapsed time to achieve partial remission across 4 groups (JAK2+/CALR+, JAK2+/CALR-, JAK2-/CALR+, JAK2-/CALR-) were reviewed. The JAK2+/CALR- group had higher leukocyte counts and hemoglobin levels and more frequent thrombotic events than JAK2-/CALR- group. JAK2 mutations have a greater effect on the disease phenotype and the clinical features of MPN patients rather than do CALR mutation. JAK2+ groups showed a tendency of poor PFS than JAK2- groups regardless of CALR mutation. CALR+ was a predictor of late response to the treatment. Our study also showed that thrombosis was more frequent in ET patients with type 2 CALR mutations than in those with type 1 CALR mutations.
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea.|Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: Min-Gu
authors.initials: MG
authors.lastname: Kang
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea.
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Choi
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea.
authors.forename: Jun Hyung
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea.
authors.forename: Yong Jun
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea.
authors.forename: Soon-Pal
authors.initials: SP
authors.lastname: Suh
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Szardenings
authors.affiliation: College of Korean Medicine, Dongshin University, Naju, Jeollanam-do, South Korea.
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea.|Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, South Korea.|Environmental Health Center for Childhood Leukemia and Cancer, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea.
authors.forename: Myung-Geun
authors.initials: MG
authors.lastname: Shin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D037282:Calreticulin / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D055728:Primary Myelofibrosis / Q000235:genetics*; D012074:Remission Induction; D013920:Thrombocythemia, Essential / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; D006454:Hemoglobins; D016044:Fusion Proteins, bcr-abl; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: calreticulin; coexistence; essential thrombocythemia; myeloproliferative disorders; Janus kinase 2