[Correlation between ASXL1 Gene Mutation Characteristics and Clinical Manifestations and Prognosis in Patients with...

To explore the correlation between ASXL1 gene mutation characteristics and clinical manifestations and prognosis in patients with myelodysplastic syndrome (MDS).

The clinical date of 264 patients with MDS in Xuzhou Central Hospital, Southeast University from August 2010 to April 2024 was retrospectively analyzed. The patients were divided into ASXL1 ^wt group and ASXL1^mut group according to the presence of ASXL1 gene mutation, and the correlation between gene mutation characteristics and clinical manifestations and prognosis was analyzed.

Compared with ASXL1^wt group, the ASXL1 ^mut group had a higher age of onset (P < 0.05), a higher proportion of males (P < 0.05), while the incidence of del(5q) was lower (P < 0.01). The mutation frequency of ASXL1 in MDS patients was 21.97%, and most of them were frameshift mutations. The p.Gly646fs was the most common amino acid variant, with a mutation frequency of 20.69%. The median overall survival (OS) and leukemia-free survival of patients with this sequence variant was 18.1 and 23.8 months, respectively, while in those without this sequence variant was 30 months and not reached, and the differences were statistically significant (P < 0.05). The results of multivariate analysis showed that the mutation of NRAS, WT1, KIT gene and the p.Gly646fs sequence mutation of ASXL1 gene were independent prognostic factors for OS in ASXL1^mut patients. The median OS of ASXL1^wt and ASXL1^mut patients was 27.9(21.3-40.4) and 23.7(18.6-NA) months, respectively (P >0.05). Among 58 ASXL1^mut patients, 5 cases (8.6%) transformed to acute leukemia, including 3 cases with RUNX1 mutation and 3 cases with TET2 mutation. Among 206 ASXL1^wt patients, 28 cases (13.6%) transformed to acute leukemia. The difference in leukemia transformation rate between the two groups was not statistically significant (P >0.05). The efficacy of different treatment regimens was similar in the ASXL1^mut group, while in the ASXL1^wt group, patients receiving allogeneic hematopoietic stem cell transplantation had a significantly better prognosis than those receiving other treatment regimens (P < 0.001). The overall response rate to demethylation therapy was 68.7% and 67.6% in ASXL1^mut and ASXL1^wt group, respectively, and the difference between the two groups was not significant (P >0.05).

The overall survival of MDS patients with ASXL1^mut is poor. The patients with p.Gly646fs sequence mutation have a higher proportion of bone marrow blasts and a worse prognosis. There are no statistical differences in efficacy of different treatment strategies in ASXL1^mut group. ASXL1 mutation shows no significant effect on the response of MDS to hypomethylating agent therapy.