[Analysis of ASXL1 gene variant in patients with myelodysplastic syndrome]

To detect ASXL1 gene variants among patients with myelodysplastic syndrome (MDS) and explore their correlation with variants of other genes and clinical features of patients.

For 149 patients with MDS, genomic DNA was amplified by PCR and subject to direct sequencing to identify variants of ASXL1, U2AF1, SF3B1, DNMT3A, TET2, IDH1/2, NPM1, FLT3-ITD and C-KIT genes.

ASXL1 variants were found among 37 patients (24.8%). Other commonly mutated genes included U2AF1 (22.8%), TET2 (11.4%), DNMT3A (9.4%), NPM1 (8.1%) and SF3B1 (6.0%). The frequency of concurrent U2AF1 and TET2 variants among patients with ASXL1 variants was slightly higher than that of wild-type patients. No significant difference was found in median age, MDS subtype, karyotype, peripheral leukocytes, hemoglobin, platelet levels, and bone marrow blast counts between the ASXL1-variant and the wild-type groups (P> 0.05). Twenty-nine patients harboring ASXL1 variants were followed up, 37.9% progressed to acute myeloid leukemia (AML). The rate of transformation in ASXL1-variant group was significantly higher than the wild-type group (37.9% vs. 14.1%, P< 0.01).

ASXL1 showed a high frequency of variant among MDS patients, which was frequently accompanied with U2AF1 and TET2 variants. Compared with the wild type group, patients with ASXL1 variants were more likely to progress to AML.