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Combination of myeloproliferative neoplasm driver gene activation with mutations of splice factor or epigenetic modifier genes increases risk of rapid blastic progression.
Bartels, Stephan; Vogtmann, Julia; Schipper, Elisa; Büsche, Guntram; Schlue, Jerome; Lehmann, Ulrich; Kreipe, Hans.
Afiliação
  • Bartels S; Institut für Pathologie, Medizinische Hochschule Hannover, Hannover, Germany.
  • Vogtmann J; Institut für Pathologie, Medizinische Hochschule Hannover, Hannover, Germany.
  • Schipper E; Institut für Pathologie, Medizinische Hochschule Hannover, Hannover, Germany.
  • Büsche G; Institut für Pathologie, Medizinische Hochschule Hannover, Hannover, Germany.
  • Schlue J; Institut für Pathologie, Medizinische Hochschule Hannover, Hannover, Germany.
  • Lehmann U; Institut für Pathologie, Medizinische Hochschule Hannover, Hannover, Germany.
  • Kreipe H; Institut für Pathologie, Medizinische Hochschule Hannover, Hannover, Germany.
Eur J Haematol ; 106(4): 520-528, 2021 Apr.
Article em En | MEDLINE | ID: mdl-33460496
OBJECTIVES: Myeloproliferative neoplasms (MPN) comprising polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) follow a bi-phasic course of disease with fibrotic and/or blastic progression. At presentation in the chronic phase, currently there are only insufficient tools to predict the risk of progression in individual cases. METHODS: In this study, chronic phase MPN (16 PMF, 11 PV, and 11 MPN unclassified) with blastic transformation during course of disease (n = 38, median follow-up 5.3 years) were analyzed by high-throughput sequencing. MPN cases with a comparable follow-up period and without evidence of blast increase served as control (n = 63, median follow-up 5.8 years). RESULTS: Frequent ARCH/CHIP-associated mutations (TET2, ASXL1, DNMT3A) found at presentation were not significantly associated with blastic transformation. By contrast, mutations of SRSF2, U2AF1, and IDH1/2 at first presentation were frequently observed in the progression cohort (13/38, 34.2%) and were completely missing in the control group without blast transformation during follow-up (P = .0007 for SRSF2; P = .0063 for U2AF1 and IDH1/2). CONCLUSION: Unlike frequent ARCH/CHIP alterations (TET2, ASXL1, DNMT3A), mutations in SRSF2, IDH1/2, and U2AF1 when manifest already at first presentation provide an independent risk factor for rapid blast transformation of MPN.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oncogenes / Ativação Transcricional / Epigênese Genética / Genes Modificadores / Fatores de Processamento de RNA / Mutação / Transtornos Mieloproliferativos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Child, preschool / Female / Humans / Infant / Male / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oncogenes / Ativação Transcricional / Epigênese Genética / Genes Modificadores / Fatores de Processamento de RNA / Mutação / Transtornos Mieloproliferativos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Child, preschool / Female / Humans / Infant / Male / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article