Abstract: Objective To study the spectrum of gene mutation and its clinical significance in myeloid malignancy patients with ASXL1 mutation. Methods The 112-gene targeted sequencing was used to analyze 1 335 patients with myeloid malignancies. The impact of gene mutation on clinical characteristics and prognosis of patients with ASXL1 mutations was analyzed. Results There were 138 (9.2%) patients with ASXL1 mutation including myelodysplastic syndromes (MDS, n=52, 37.68%), myeloproliferative neoplasms (MPN, n=29, 21.01%), MDS/MPN (n=10, 7.25%), and acute myeloid leukemia (AML, n=47, 34.06%). Eighty-nine mutation genes were found in 138 patients, and 96.4% (133) of the patients were accompanied by more than one gene mutation. Among them, epigenetic genes were 55.8% (77 / 138), signal transduction pathway gene, spliceosome 65.9% (91/138), transcription factor 36.9% (51/138), and cell cycle and apoptosis related genes 18.8% (26 / 138). The most common co-mutation genes were RAS 25.4%, SETBP1 21.7%, FAT1 18.8%,CREBBP 15.9% and TET2 15.2%. Compared with patients with ASXL1+RAS-, patients with ASXL1+RAS+ showed a worse prognosis, with decreased hemoglobin and platelet, increased chromosome karyotype abnormality rate, and significantly lower survival. There were no significant differences in the clinical features and prognosis between patients with SETBP1,FAT1, CREBBP and TET2 mutation combined with ASXL1. Conclusion We provide a comprehensive overview of the spectrum, clinical associations and prognostic relevance of gene co-mutations with ASXL1 in patients with myeloid malignancies. Patients with co-mutation of ASXL1 and RAS pathway gene have a worse prognosis.

Key words: leukemia, ASXL1 mutation, myeloid malignancies, next generation sequencing, co-mutation