Cytogenetics, JAK2 and MPL mutations in polycythemia vera, primary myelofibrosis and essential thrombocythemia

Cytogenetics, JAK2 and MPL mutations in polycythemia vera, primary myelofibrosis and essential thrombocythemia

Autor Santos, Leonardo Caires dos Autor UNIFESP Google Scholar
Ribeiro, Juliana Corrêa da Costa Autor UNIFESP Google Scholar
Silva, Neusa Pereira da Autor UNIFESP Google Scholar
Cerutti, Janete Maria Autor UNIFESP Google Scholar
Silva, Maria Regina Regis da Autor UNIFESP Google Scholar
Chauffaille, Maria de Lourdes Lopes Ferrari Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo BACKGROUND: The detection of molecular and cytogenetic alterations is important for the diagnosis, prognosis and classification of myeloproliferative neoplasms. OBJECTIVE: The aim of this study was to detect the following mutations: JAK2 V617F, JAK2 exon 12 and MPL W515K/L, besides chromosomal abnormalities. Furthermore, molecular and cytogenetic alterations were correlated with the leukocyte and platelet counts, hemoglobin levels and age in all patients and with the degree of fibrosis in primary myelofibrosis cases. METHODS: Twenty cases of polycythemia vera, 17 of essential thrombocythemia and 21 of primary myelofibrosis were selected in the Hematology Department of the Universidade Federal de São Paulo (UNIFESP) between February 2008 and December 2009. The JAK2 V617F, JAK2 exon 12 mutations, MPL W515K and MPL W515L mutations were investigated by real-time PCR and direct sequencing. G-band karyotyping and fluorescence in situ hybridization were used to detect chromosomal abnormalities. RESULTS: Chromosomal abnormalities were observed only in polycythemia vera (11.8%) and primary myelofibrosis cases (17.6%), without correlation to clinical data. Chromosomal abnormalities were not detected by fluorescence in situ hybridization. The JAK2 V617F mutation was observed in polycythemia vera (90%), primary myelofibrosis (42.8%) and essential thrombocythemia (47%). Patients with JAK2 V617F-negative polycythemia vera had lower platelet and leukocyte counts compared to V617F-positive polycythemia vera (p-value = 0.0001 and p-value = 0.023, respectively). JAK2 V617F-positive and MPL W515L-positive primary myelofibrosis cases had a higher degree of fibrosis than V617F-negative cases (p-value = 0.022). JAK2 exon 12 mutations were not detected in polycythemia vera patients. The MPL W515L mutation was observed in one case of primary myelofibrosis and in one of essential thrombocythemia. The MPL W515K mutation was not found in patients with essential thrombocythemia or primary myelofibrosis. The MPL W515L-positive patient with primary myelofibrosis had more severe anemia than other patients with primary myelofibrosis. CONCLUSIONS: This study demonstrates that karyotyping for JAK2 and MPL mutations is useful in the diagnosis of myeloproliferative neoplasms. The precise pathogenetic contribution of these alterations is still unclear. However, this study adds more information about the pathophysiology of polycythemia vera, essential thrombocythemia and primary myelofibrosis.
Palavra-chave Myeloproliferative disorders
Cytogenetic analysis
Karyotype
Molecular biology, Thrombocythemia, essential
Polycythemia vera
Idioma Inglês
Data de publicação 2011-12-01
Publicado em Revista Brasileira de Hematologia e Hemoterapia. Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular, v. 33, n. 6, p. 417-424, 2011.
ISSN 1516-8484 (Sherpa/Romeo)
Publicador Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular
Extensão 417-424
Fonte http://dx.doi.org/10.5581/1516-8484.20110116
Direito de acesso Acesso aberto Open Access
Tipo Artigo
SciELO S1516-84842011000600009 (estatísticas na SciELO)
Endereço permanente http://repositorio.unifesp.br/handle/11600/6774

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