Impact of ASXL1 Gene Alterations on Myelodysplastic Syndrome With Isolated 20q Deletion

作者：Yanan Chang, Linlin Liu, Chenghua Cui, Jiange He, Chengwen Li, Yujiao Jia, Ruixue Zhang, W.J. Wu, Ji Zhou, Jigang Xiao, Zefeng Xu, Tiejun Qin, Qi Sun, Huijun Wang, Zhijian Xiao · 发表于：Cancer Medicine · 年份：2025 · DOI：10.1002/cam4.70747 · 研究领域：Acute Myeloid Leukemia Research、Genomic variations and chromosomal abnormalities、Genetic factors in colorectal cancer

ABSTRACT Background Isolated 20q deletion [del(20q)] is a recurrent favorable abnormality in myelodysplastic syndrome (MDS) and may cause deletion of the ASXL1 gene. Meanwhile, ASXL1 mutations are also common in individuals with MDS. This study aimed to describe the biological and clinical implications of ASXL1 mutations and deletion in newly diagnosed MDS patients with isolated del(20q). Methods Gene mutation and copy number alterations in 178 newly diagnosed MDS patients with isolated del(20q) were analyzed using DNA next generation sequencing. Results Twenty‐five (14%) of 178 patients were found to have ASXL1 mutations, which exhibited lower absolute neutrophil counts (ANC) ( p = 0.006), a higher percentage of bone marrow blasts ( p = 0.001), more mutant genes ( p < 0.001), higher IPSS‐R ( p = 0.038) and IPSS‐M ( p = 0.001) risk groups. Furthermore, ASXL1 mutations were preferentially associated with mutations in U2AF1 , and most ASXL1 mutations (68%) were observed as subclonal lesions. ASXL1 frameshift mutations were associated with a worse prognosis in MDS patients with low blasts (MDS‐LB) ( p = 0.043), but not in those with increased blasts (MDS‐IB). Twenty‐two (26.8%) of 82 patients were found to have ASXL1 deletion, which exhibited a lower IPSS‐M risk group, lower platelet counts, higher ANC levels, and higher hemoglobin levels compared to ASXL1 patients only‐mut and ASXL1 wt patients. Two (2.4%) of the 82 patients exhibited biallelic ASXL1 inactivation ( ASXL1 mut...