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Ann Hematol. 2019 Apr;98(4):869-879. doi: 10.1007/s00277-018-3563-7. Epub 2018 Dec 4.

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

Author information

1
Department of Medicine, The University of Hong Kong, Hong Kong, China.
2
Department of Pathology, Queen Mary Hospital, Hong Kong, China.
3
School of Public Health, The University of Hong Kong, Hong Kong, China.
4
The Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong, China.
5
Systems Biology Group, School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
6
Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.
7
Department of Medicine, The University of Hong Kong, Hong Kong, China. ylkwong@hkucc.hku.hk.
8
Department of Medicine, Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong, China. ylkwong@hkucc.hku.hk.

Abstract

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 × 109/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 × 109/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.

KEYWORDS:

Myelofibrosis; Next-generation sequencing; Primary; Prognosis; Secondary

PMID:
30515541
DOI:
10.1007/s00277-018-3563-7
[Indexed for MEDLINE]

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