108 例骨髓增殖性肿瘤患者基因突变与临床特征分析

OBJECTIVE: To analyze the genetic mutations and clinical features of the subtypes of classical BCR-ABL-negative myeloproliferative neoplasm (MPN). METHODS: Mutations of 108 newly diagnosed BCR-ABL-negative MPN patients [including 55 patients with essential thrombocytopenia (ET), 24 with polycythemia vera (PV), and 29 with primary myelofibrosis (PMF)] were identified using next-generation sequencing with 127-gene panel, and the relationship between gene mutations and clinical features were analyzed. RESULTS: Total 211 mutations in 32 genes were detected in 100 MPN patients (92.59%), per capita carried (1.96±1.32) mutations. 85.19% (92/108) patients carried the driver gene (JAK2, CALR, MPL) mutations, 69.56% (64/92) of these patients carried at least 1 additional gene mutation. In descending order of mutation frequency, the highest frequency was for activation signaling pathway genes (42.2%, 89/211), methylation genes (17.6%, 36/211), and chromatin-modified genes (16.1%, 34/211). There was a significant difference in the number of mutations in the activation signaling pathway genes, epigenetic regulatory genes, spliceosomes, and RNA metabolism genes among the three MPN subgroups. The average number of additional mutations in PMF patients was higher than that in ET and PV patients (1.69±1.39, 0.67±0.70, 0.87±1.22, χ(2)=13.445, P=0.001). MPN-SAF-TSS (MPN 10 score) (P=0.006) and myelofibrosis level (P=0.015) in patients with ≥3 mutant genes were higher and the HGB level (P=0.002) was lower than in those with<3 mutations. Twenty-six patients (24.1%) carried high-risk mutation (HMR), and patients with HMR had lower PLT (P=0.017), HGB levels (P<0.001), and higher myelofibrosis level (P=0.010) and MPN10 score (P<0.001). The frequency of ASXL1 mutations was higher in PMF than in PV patients (34.5% vs. 4.2%, P=0.005). PMF patients with ASXL1 had lower levels of PLT and HGB (P=0.029 and 0.019). CONCLUSION: 69.56% of MPN patients carry at least one additional mutation, and 24.1% patients had HMR. Each subgroup had different mutation patterns. PMF patients had a higher average number of additional gene mutations, especially a higher frequency of ASXL1 mutation; PLT and HGB levels were lower in ASXL1 mutation PMF patients.