RESUMO
No abstract available.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fatores Etários , Sequência de Aminoácidos , Calreticulina/genética , DNA/química , Éxons , Janus Quinase 2/genética , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Receptores de Trombopoetina/genética , Análise de Sequência de DNA , Fatores Sexuais , Trombocitemia Essencial/diagnósticoRESUMO
Mutations in the calreticulin gene, CALR, have recently been discovered in subsets of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). We investigated Korean patients with ET and PMF to determine the prevalence, and clinical and laboratory correlations of CALR/JAK2/MPL mutations. Among 84 ET patients, CALR mutations were detected in 23 (27.4%) and were associated with higher platelet counts (P=0.006) and lower leukocyte counts (P=0.035) than the JAK2 V617F mutation. Among 50 PMF patients, CALR mutations were detected in 11 (22.0%) and were also associated with higher platelet counts (P=0.035) and trended to a lower rate of cytogenetic abnormalities (P=0.059) than the JAK2 V617F mutation. By multivariate analysis, triple-negative status was associated with shorter overall survival (HR, 7.0; 95% CI, 1.6-31.1, P=0.01) and leukemia-free survival (HR, 6.3; 95% CI, 1.8-22.0, P=0.004) in patients with PMF. The type 1 mutation was the most common (61.1%) type among all patients with CALR mutations, and tended toward statistical predominance in PMF patients. All 3 mutations were mutually exclusive and were never detected in patients with other myeloid neoplasms showing thrombocytosis. CALR mutations characterize a distinct group of Korean ET and PMF patients. Triple-negative PMF patients in particular have an unfavorable prognosis, which supports the idea that triple-negative PMF is a molecularly high-risk disease.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Calreticulina/genética , Intervalo Livre de Doença , Frequência do Gene , Estudos de Associação Genética , Janus Quinase 2/genética , Mutação/genética , Mielofibrose Primária/genética , Receptores de Trombopoetina/genética , República da Coreia , Trombocitemia Essencial/genéticaRESUMO
BACKGROUND: Calreticulin (CALR) mutations were recently discovered in patients with myeloproliferative neoplasms (MPNs). We studied the frequency and type of CALR mutations and their hematological characteristics. METHODS: A total of 168 MPN patients (36 polycythemia vera [PV], 114 essential thrombocythemia [ET], and 18 primary myelofibrosis [PMF] cases) were included in the study. CALR mutation was analyzed by the direct sequencing method. RESULTS: CALR mutations were detected in 21.9% of ET and 16.7% of PMF patients, which accounted for 58.5% and 33.3% of ET and PMF patients without Janus kinase 2 (JAK2) or myeloproliferative leukemia virus oncogenes (MPL) mutations, respectively. A total of five types of mutation were detected, among which, L367fs*46 (53.6%) and K385fs*47 (35.7%) were found to be the most common. ET patients with CALR mutation had lower leukocyte counts and ages compared with JAK2-mutated ET patients. CONCLUSION: Genotyping for CALR could be a useful diagnostic tool for JAK2-or MPL-negative ET or PMF patients. CALR mutation may be a distinct disease group, with different hematological characteristics than that of JAK2-positive patients.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Sequência de Aminoácidos , Sequência de Bases , Calreticulina/genética , Análise Mutacional de DNA , Éxons , Janus Quinase 2/genética , Contagem de Leucócitos , Dados de Sequência Molecular , Mutação , Transtornos Mieloproliferativos/diagnóstico , Receptores de Trombopoetina/genéticaRESUMO
No abstract available.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Medula Óssea/patologia , Calreticulina/genética , Eritropoetina/sangue , Proteínas de Fusão bcr-abl/genética , Hematócrito , Hemoglobinas/análise , Janus Quinase 2/genética , Mutação , Transtornos Mieloproliferativos/diagnóstico , Policitemia Vera/diagnóstico , Receptores de Trombopoetina/genética , Trombocitemia Essencial/diagnóstico , Organização Mundial da SaúdeAssuntos
Humanos , Masculino , Feminino , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/genética , Mielofibrose Primária/tratamento farmacológico , Eritropoetina/uso terapêutico , Fatores Imunológicos/uso terapêutico , /genética , Mutação , Prognóstico , Receptores de Trombopoetina/genética , Translocação GenéticaRESUMO
JAK2 V617F and MPL W515L/K mutations have been reported in approximately 50% and 5% of the patients with essential thrombocythemia (ET), respectively. We investigated the frequency of MPL W515L/K mutations in a series of consecutive patients with ET and post-essential thrombocythemia myelofibrosis (post-ET MF). The study subjects were 63 patients diagnosed either with ET (N=59) or post-ET MF (N=4) at our institution between June 2006 and February 2010. Among them, 35 (55.6%) had the JAK2 V617F mutation. MPL W515L/K mutations were detected by direct sequencing analyses of exon 10, and 2 patients were found to harbor the following MPL mutations: W515L in 1 patient with ET and W515K in 1 patient with post-ET MF. Neither of the patients had the JAK2 V617F mutation. The frequencies of the MPL W515L/K and JAK2 V617F-negative mutations in our subjects with ET/post-ET MF were 3.2% (2/63) and 7.1% (2/28), respectively. This is the first study to report the frequency of JAK2 V617F and MPL W515L/K mutations in Korean patients with ET/post-ET MF.