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ASXL1 Mutations Associated With Worse Prognosis in MDS and AML


A recent meta-analysis found ASXL1 mutations to be independent risk factors for worse overall survival and transformation to acute myeloid leukemia in patients with myelodysplastic syndromes (MDS), as well as worse overall survival in acute myeloid leukemia (AML).

Many studies have identified additional sex combs-like 1 (ASXL1) mutations in patients with myelodysplastic syndrome (MDS), but data on their potential prognostic value have not been definitive. A recent meta-analysis published in the Asia-Pacific Journal of Clinical Oncology found ASXL1 mutations to be independent risk factors for worse overall survival (OS) and transformation to acute myeloid leukemia (AML).

MDS encompasses a group of hematopoietic stem cell diseases that cause peripheral cytopenia and can potentially transform into AML. ASXL1 is often found to be mutated in cases of bone marrow tumors such as MDS and AML, but the role of these mutations is not clear. The goal of the meta-analysis was to examine the relationship between ASXL1 mutations and prognosis in MDS.

To study the prognostic impact of ASXL1 in patients with MDS, researchers initially identified a total of 2364 studies in the PubMed, Embase, and Cochrane Library databases. After excluding repetitive articles, review articles, case reports, laboratory studies, meeting minutes, studies that did not focus on the prognostic value of ASXL1 mutations in MDS, and articles with insufficient data, 10 studies were included in the meta-analysis.

Of the 10 studies reporting on ASXL1 in MDS, 9 reported on multivariate hazard ratios (HRs) for overall survival (OS), 3 reported on univariate HRs for OS, and 2 reported on multivariate HRs for transformation to AML.

ASXL1 mutations were found to have an adverse prognostic impact on OS in patients with MDS (HR, 1.68; 95% CI, 1.45-1.94, P < .0001). They were also associated with AML transformation (HR, 2.20; 95% CI, 1.68-2.87, P < .0001). The association between mutations and OS was similar regardless of age group.

A total of 2416 studies were initially identified to explore the impact of ASXL1 mutations on AML prognosis. After a similar exclusion process, 10 studies were included in the final meta-analysis of ASXL1 in AML. Of these studies, 7 reported multivariable HRs for OS, 4 reported univariate HRs for OS, 3 provided multivariable HRs for OS when patients were aged 60 years of age or older, and 3 studies provided HRs for OS of cytogenetically normal AML (CN-AML).

In patients with AML, ASXL1 mutations were associated with poorer OS (HR, 1.37; 95% CI, 1.20-1.56, P < .0001). In the cohort of patients aged 60 years or older, the association was especially strong (HR, 2.86; 95% CI, 1.34-6.08; P = .006). In CN-AML, there was still an association between mutations and poorer OS (HR, 1.78; 95% CI, 1.27-2.49; P = .001).

“The results of our meta-analysis show that patients with MDS and ASXL1 mutations had a shorter OS than those without the mutation. This result is consistent with a previous meta-analysis,” the authors wrote. “… When exploring the effect of ASXL1 mutations on the prognosis of patients with AML, we found that patients with AML and ASXL1 mutations had shorter OS than patients without mutations, which is consistent with previous studies.”

In addition to prognostic value regarding OS, the findings suggest that ASXL1 mutations in MDS also increase the likelihood of transformation to AML. Only 2 studies were included in the meta-analysis for this specific outcome, but the authors conclude that the results are significant.

Taken together, the meta-analysis suggests that ASXL1 mutations are independently associated with worse OS in MDS and AML, as well as transformation to AML in patients with MDS. These findings could apply to prognostication for MDS and AML patients, as well as help guide treatment strategies. Prospective randomized controlled trials would be beneficial to assess the impact of ASXL1 mutations in tandem with other clinical characteristics.


Zhang A, Wang S, Ren Q, Wang Y, Jiang Z. Prognostic value of ASXL1 mutations in patients with myelodysplastic syndromes and acute myeloid leukemia: A meta-analysis. Asia Pac J Clin Oncol. Published online December 5, 2022. doi:10.1111/ajco.13897.

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