Correlation between epigenetic modifier gene mutations and prognosis of patients with acute lymphoblastic leukemia: a systematic review and meta-analysis.
Rui-Qi Wang, Bing Han, Hai-Yu Song et al.
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In 30 seconds
This systematic review and meta-analysis assessed whether epigenetic modifier gene mutations are associated with survival in acute lymphoblastic leukemia (ALL). Across 19 studies, DNMT3A mutation was associated with worse overall survival (OS) in ALL (HR, 4.143; P < 0.001), including adult T-ALL and early T-ALL. IDH mutations were also associated with poorer OS in ALL and adult T-ALL. PHF6 and KMT2A mutations showed adverse associations in specified patient groups, while other assessed mutations had no reported prognostic impact.
Key findings
- DNMT3A mutation was associated with worse OS in ALL (HR, 4.143; P < 0.001), adult T-ALL (HR, 3.746; P < 0.001), and early T-ALL (HR, 3.523; P = 0.001).
- IDH mutation was associated with unfavorable OS in ALL (HR, 3.583; P < 0.001) and adult T-ALL (HR, 3.562; P < 0.001).
- In pediatric patients, PHF6 mutation was associated with worse OS in B-ALL (HR, 3.194; P = 0.026) and T-ALL (HR, 2.125; P = 0.033).
- KMT2A mutation was associated with shorter OS than wild type (HR, 4.605; P = 0.045); PHF6 had no prognostic impact in adult T-ALL.
Why it matters
The findings suggest that the prognostic relevance of epigenetic modifier mutations in ALL varies by gene and patient subtype. Identifying these associations may help refine prognostic assessment and inform research into risk stratification, although the pooled results do not establish that mutation status should determine treatment.