title: Frequencies, Laboratory Features, and Granulocyte Activation in Chinese Patients with CALR-Mutated Myeloproliferative Neoplasms.
abstract: Somatic mutations in the CALR gene have been recently identified as acquired alterations in myeloproliferative neoplasms (MPNs). In this study, we evaluated mutation frequencies, laboratory features, and granulocyte activation in Chinese patients with MPNs. A combination of qualitative allele-specific polymerase chain reaction and Sanger sequencing was used to detect three driver mutations (i.e., CALR, JAK2V617F, and MPL). CALR mutations were identified in 8.4% of cases with essential thrombocythemia (ET) and 5.3% of cases with primary myelofibrosis (PMF). Moreover, 25% of polycythemia vera, 29.5% of ET, and 48.1% of PMF were negative for all three mutations (JAK2V617F, MPL, and CALR). Compared with those patients with JAK2V617F mutation, CALR-mutated ET patients displayed unique hematological phenotypes, including higher platelet counts, and lower leukocyte counts and hemoglobin levels. Significant differences were not found between Chinese PMF patients with mutants CALR and JAK2V617F in terms of laboratory features. Interestingly, patients with CALR mutations showed markedly decreased levels of leukocyte alkaline phosphatase (LAP) expression, whereas those with JAK2V617F mutation presented with elevated levels. Overall, a lower mutant rate of CALR gene and a higher triple-negative rate were identified in the cohort of Chinese patients with MPNs. This result indicates that an undiscovered mutant gene may have a significant role in these patients. Moreover, these pathological features further imply that the disease biology varies considerably between mutants CALR and JAK2V617F.
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China; Department of Microbiology and Immunology, School of Basic Medicine, Shanxi Medical University, Taiyuan, China.
authors.forename: Haixiu
authors.initials: H
authors.lastname: Guo
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Ruiyuan
authors.initials: R
authors.lastname: Tian
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Chang
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Jianlan
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Fanggang
authors.initials: F
authors.lastname: Ren
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Jianxia
authors.initials: J
authors.lastname: He
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Wanfang
authors.initials: W
authors.lastname: Yang
authors.affiliation: Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D037282:Calreticulin / Q000235:genetics*; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006098:Granulocytes / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D053628:Receptors, Thrombopoietin / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2