Combination of myeloproliferative neoplasm driver gene activation with mutations of splice factor or epigenetic modifier genes increases risk of rapid blastic progression.
Eur J Haematol
; 106(4): 520-528, 2021 Apr.
Article
en En
| MEDLINE
| ID: mdl-33460496
ABSTRACT
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Oncogenes
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Activación Transcripcional
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Epigénesis Genética
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Genes Modificadores
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Factores de Empalme de ARN
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Mutación
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Trastornos Mieloproliferativos
Tipo de estudio:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Child, preschool
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Female
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Humans
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Infant
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Haematol
Asunto de la revista:
HEMATOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania