RESUMO
AIMS: The purpose of this study was to compare the DNA-methylation signature in classic chronic Philadelphia negative myeloproliferative neoplasms (MPN), polycythaemia vera (PV) and essential thrombocythaemia (ET), in order to obtain a global insight into DNA-methylation changes associated with these malignancies. METHODS: Thirty-five MPN samples from 11 ET JAK2 V617F, 12 ET JAK2 wild type (WT) and 12 PV JAK2 V617F patients as well as 12 from healthy donors were analysed. DNA samples extracted from whole peripheral blood were hybridised to the 'HumanMethylation27 DNA Analysis BeadChip.' RESULTS: All groups showed a very homogeneous methylation pattern. Only the ZNF577 gene showed a differential methylation profile between PV JAK2 V617F positive and controls. This aberrant methylation was correlated with a differential gene expression of ZNF577. No aberrant hypermethylation was found in the SOCS-1 and SOCS-3 genes. CONCLUSIONS: According to our results, an aberrant methylation pattern does not seem to play a crucial role in MPN pathogenesis; nor does it justify phenotypical differences between PV and ET.
Assuntos
Metilação de DNA/genética , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Policitemia Vera/genética , Trombocitemia Essencial/genética , Adulto , Idoso , DNA de Neoplasias/genética , Proteínas de Ligação a DNA/genética , Epigenômica , Feminino , Humanos , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Proteína 1 Supressora da Sinalização de Citocina , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Fatores de Transcrição/genéticaRESUMO
Several cases of systemic amyloidosis associated with polymyalgia rheumatica (PMR) or giant-cell arteritis (GCA) have been described. Nevertheless, the type of amyloid deposit has not been characterized in most of them. Here we report on two patients with PMR (one with associated GCA) who developed nephrotic syndrome and end-stage renal failure caused by massive amyloid deposition. Immunohistochemical analysis showed that the amyloid deposits were of AA type (secondary amyloidosis) in both cases.
