title: CALR mutations screening in wild type JAK2(V617F) and MPL(W515K/L) Brazilian myeloproliferative neoplasm patients.
abstract: Some myeloproliferative neoplasm (MPN) patients harbor JAK2(V617F) mutation, and CALR mutations were recently discovered in wild type (WT) JAK2(V617F). We evaluated the frequency and type of CALR mutations, and clinical and hematological characteristics in WT JAK2(V617F) and MPL(W515K/L) MPN patients. Sixty-five patients were included: 21 with primary myelofibrosis (PMF), 21 with myelofibrosis post-essential thrombocythemia (MPET) and 23 with essential thrombocythemia (ET). Screening for JAK2(V617F) and MPL(W515K/L) were performed using real-time PCR, while CALR mutations were analyzed by fragment analysis and Sanger sequencing. JAK2(V617F) was the most frequent mutation (54.5%) and one patient (1.5%) harbored MPL(W515L). CALR mutations were present in 38.1% of PMF, 12.5% of ET and 33.3% of MPET patients. Five types of CALR mutations were detected, among which type 1 (32.1%) and type 2 (21.4%) were found to be the most common. A novel CALR mutation in a PMF patient was found. Patients carrying CALR mutations had higher platelet count and less presence of splenomegaly than JAK2(V617F), while triple negatives had higher C-reactive protein levels than CALR mutant carriers. Screening for CALR mutations and its correlation with clinical features could be useful for the characterization of MPN patients and result in its incorporation into a new prognostic score.
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Daniela Prudente Teixeira
authors.initials: DP
authors.lastname: Nunes
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Luciene Terezina de
authors.initials: LT
authors.lastname: Lima
authors.affiliation: Departamento de Hematologia e Hemoterapia da Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Maria de Lourdes
authors.initials: Mde L
authors.lastname: Chauffaille
authors.affiliation: Grupo Fleury, Pesquisa e Desenvolvimento, São Paulo, Brazil.
authors.forename: Miguel
authors.initials: M
authors.lastname: Mitne-Neto
authors.affiliation: Grupo Fleury, Pesquisa e Desenvolvimento, São Paulo, Brazil.
authors.forename: Marcos Tadeu dos
authors.initials: MT
authors.lastname: Santos
authors.affiliation: Departamento de Hematologia, Complexo Hospitalar de Sorocaba, Universidade Católica de São Paulo, Sorocaba, São Paulo, Brazil.
authors.forename: Marcelo Gil
authors.initials: MG
authors.lastname: Cliquet
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, São Paulo, Brazil. Electronic address: emguerra@usp.br.
authors.forename: Elvira Maria
authors.initials: EM
authors.lastname: Guerra-Shinohara
mesh_terms: D001938:Brazil; D037282:Calreticulin / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D059645:Mutation Rate; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism*; D010976:Platelet Count; D060888:Real-Time Polymerase Chain Reaction; D013926:Thrombopoietin / Q000378:metabolism
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; D013926:Thrombopoietin; D053614:Janus Kinase 2
keywords: CALR; Essential thrombocythemia; JAK2(V617F); Myelofibrosis; Myeloproliferative neoplasms