Non-driver mutations landscape in different stages of primary myelofibrosis determined ASXL1 mutations play a critical role in disease progression
Xin Yan, Zefeng Xu, Peihong Zhang, Qi Sun, Yujiao Jia, Tiejun Qin, Shiqiang Qu, Lijuan Pan, Zhanqi Li, Jinqin Liu, Zhen Song, Qingyan Gao, Meng Jiao, Jingye Gong, Huijun Wang, Bing Li, Zhijian Xiao
Abstract
In primary myelofibrosis (PMF), there is a stepwise evolution from an initial prefibrotic (Pre)/early stage, characterized by hypercellular bone marrow with absent or minimal reticulin fibrosis, to an overt fibrotic (Overt) stage with marked reticulin or collagen fibrosis in the bone marrow [ 1 ] and 5–30% of patients develop to blast phase [ 2 , 3 , 4 , 5 , 6 ]. Although gene mutations were confirmed as the important prognostic factor in PMF [ 7 , 8 , 9 , 10 , 11 , 12 ], whether or not these gene mutations can predict fibrosis progression and leukemic transformation is still unclear. The aim of this study was to explore if some non-driver mutations play a key role in disease progression based on the mutational landscape in the progression of PMF. Through analyzing the non-driver mutations in different stages of PMF patients, we found that ASXL1 mutations were significantly associated with both the exacerbation of fibrosis and the leukemic transformation.