Next-generation sequencing with a 54-gene panel identified unique mutational profile and prognostic markers in Chinese patients with myelofibrosis

• Published in: Annals of hematology Vol. 98; no. 4; pp. 869 - 879
• Main Authors: Gill, Harinder, Ip, Ho-Wan, Yim, Rita, Tang, Wing-Fai, Pang, Herbert H., Lee, Paul, Leung, Garret M. K., Li, Jamilla, Tang, Karen, So, Jason C. C., Leung, Rock Y. Y., Li, Jun, Panagioutou, Gianni, Lam, Clarence C. K., Kwong, Yok-Lam
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2019; Springer Nature B.V
• Subjects: Gender; Hematology; Hemoglobin; Medical prognosis; Medicine; Medicine & Public Health; Mutation; Oncology; Original Article; Secondary; Myelofibrosis; Next-generation sequencing; Prognosis; Primary
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-018-3563-7

Current prognostication in myelofibrosis (MF) is based on clinicopathological features and mutations in a limited number of driver genes. The impact of other genetic mutations remains unclear. We evaluated for mutations in a myeloid panel of 54 genes using next-generation sequencing. Multivariate Cox regression analysis was used to determine prognostic factors for overall survival (OS) and leukaemia-free survival (LFS), based on mutations of these genes and relevant clinical and haematological features. One hundred and one patients (primary MF, N  = 70; secondary MF, N  = 31) with a median follow-up of 49 (1–256) months were studied. For the entire cohort, inferior OS was associated with male gender ( P  = 0.04), age > 65 years ( P  = 0.04), haemoglobin < 10 g/dL ( P  = 0.001), CUX1 mutation ( P  = 0.003) and TP53 mutation ( P  = 0.049); and inferior LFS was associated with male gender ( P  = 0.03), haemoglobin < 10 g/dL ( P  = 0.04) and SRSF2 mutations ( P  = 0.008). In primary MF, inferior OS was associated with male gender ( P  = 0.03), haemoglobin < 10 g/dL ( P  = 0.002), platelet count < 100 × 10 9 /L ( P  = 0.02), TET2 mutation ( P  = 0.01) and CUX1 mutation ( P  = 0.01); and inferior LFS was associated with haemoglobin < 10 g/dL ( P  = 0.02), platelet count < 100 × 10 9 /L ( P  = 0.02), TET2 mutations ( P  = 0.01) and CUX1 mutations ( P  = 0.04). These results showed that clinical and haematological features and genetic mutations should be considered in MF prognostication.