title: CALR mutation screening in pediatric primary myelofibrosis.
abstract: BACKGROUND
  Primary myelofibrosis (PMF) is quite rare in children. Mutations of JAK2(V617F) or MPL(W515K/L) were absent in pediatric patients with PMF according to previous studies. Recently, mutations in calreticulin (CALR) were described in adult patients with JAK2/MPL-unmutated PMF. Our study aimed to analyze the clinical and genetic features of Chinese pediatric patients with PMF.
  
  
  METHODS
  We retrospectively investigated 14 pediatric patients diagnosed as PMF according to WHO 2008 criteria. Direct sequencing was performed for the existence of genetic alterations in JAK2, MPL, TET2, CBL, ASXL1, IDH1, IDH2, SRSF2, EZH2, DNMT3A and CALR.
  
  
  RESULTS
  In our cohort, all patients had anemia, three patients (21%) had splenomegaly, six patients (43%) had micromegakaryocytes at time of diagnosis. No patient had spontaneous remission and six patients (43%) transformed to acute myelocytic leukemia. In nine patients with evaluable cytogenetic information, three subjects (33%) had abnormal karyotypes. The median survival from time of diagnosis was 28 months. Seven patients (50%) had type 2 mutations of CALR. No patient had mutations in the other candidate genes. There was no statistical differences in age, gender, hemoglobin, WBC, neutrophil and platelet counts, percentage of circulating blast, overall survival and leukemia transformation between patients with and without CALR mutation.
  
  
  CONCLUSIONS
  Our study documented that Chinese pediatric patients with PMF in our cohort had its own clinical characteristics and poor outcome. CALR mutations were detected in 50% of our pediatric patients with PMF. Based on our study, CALR mutations screening could be used as molecular marker for diagnosis of pediatric patients with PMF.
authors.affiliation: Pediatric Blood Diseases Centre, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: An
authors.forename: Yang
authors.initials: Y
authors.lastname: Wan
authors.forename: Ye
authors.initials: Y
authors.lastname: Guo
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chen
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ren
authors.forename: Jingliao
authors.initials: J
authors.lastname: Zhang
authors.forename: Lixian
authors.initials: L
authors.lastname: Chang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Peihong
authors.initials: P
authors.lastname: Zhang
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D037282:Calreticulin / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D055728:Primary Myelofibrosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: C576483:CALR protein, human; D037282:Calreticulin
keywords: CALR; mutation; pediatric; primary myelofibrosis