title: Diversities of Calreticulin Gene Mutations in Macedonian Patients With Essential Thrombocythemia.
abstract: Acquired calreticulin (CALR) gene mutations are one of the molecular hallmarks of essential thrombocythemia (ET). It has been suggested that patients with ET with CALR mutations are associated with a distinct clinical phenotype.
  
  
  
  We evaluated the clinical and molecular features of 150 patients with ET followed over a period of 15 years. The screening for the presence of insertion/deletion mutations in CALR exon 9 was done with a fluorescent polymerase chain reaction/capillary electrophoresis procedure. Sanger sequencing of CALR exon 9 was used for the characterization of mutations and for the analysis of triple-negative patients.
  
  
  
  CALR mutations were detected in 42 (28%) patients. The most common CALR mutations were type 1 and type 2, which were present in 11 (26.2%) and 20 (47.6%) patients, respectively. Additionally, 10 different small insertion/deletions (3 known and 7 new) were detected in 11 patients, resulting in an altered calreticulin C-terminal end. The clinical characteristics of all CALR+ patients with ET were in line with previously published data for this subset of patients.
  
  
  
  Our results showed that a wide range of different CALR mutations are associated with a distinct ET clinical phenotype that is associated with the male gender, younger age at diagnosis, higher platelet and lower leukocyte and erythrocyte counts and lower hemoglobin level, and a milder clinical course. The relatively high frequency of new insertion/deletion mutations indicate that the use of fluorescent polymerase chain reaction followed by capillary electrophoresis is the method of choice for the analysis of these defects.
authors: University Clinic for Hematology, Faculty of Medicine, University Saints Cyril and Methodius, Skopje, Republic of Macedonia. Electronic address: dr_irina@yahoo.com.
authors: Irina
authors: I
authors: Panovska-Stavridis
authors: Center of Biomolecular Sciences, Faculty of Pharmacy, University Saints Cyril and Methodius, Skopje, Republic of Macedonia.
authors: Aleksandar
authors: A
authors: Eftimov
authors: University Clinic for Hematology, Faculty of Medicine, University Saints Cyril and Methodius, Skopje, Republic of Macedonia.
authors: Martin
authors: M
authors: Ivanovski
authors: University Clinic for Hematology, Faculty of Medicine, University Saints Cyril and Methodius, Skopje, Republic of Macedonia.
authors: Aleksandar
authors: A
authors: Stojanovic
authors: University Clinic for Hematology, Faculty of Medicine, University Saints Cyril and Methodius, Skopje, Republic of Macedonia.
authors: Borce
authors: B
authors: Georgievski
authors: University Clinic for Hematology, Faculty of Medicine, University Saints Cyril and Methodius, Skopje, Republic of Macedonia.
authors: Lidija
authors: L
authors: Cevreska
authors: Center of Biomolecular Sciences, Faculty of Pharmacy, University Saints Cyril and Methodius, Skopje, Republic of Macedonia.
authors: Aleksandar J
authors: AJ
authors: Dimovski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001772:Blood Cell Count; D037282:Calreticulin / Q000235:genetics*; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D053628:Receptors, Thrombopoietin / Q000235:genetics; D016019:Survival Analysis; D013920:Thrombocythemia, Essential / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality
chemical_list: D015415:Biomarkers; D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D053614:Janus Kinase 2
keywords: CALR deletion; CALR insertion; Fluorescent PCR; KDEL motif; MPNs