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December 8, 2025BloodOpen Access

Prognostic impact of co-occurring mutations in NPM1-mutated Acute Myeloid Leukemia

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Authors

RSRafeh SafdarUniversity of KentuckyHDHardik DandUniversity of KentuckyYAYanal AlnimerUniversity of Kentucky

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Overview

Retrospective review shows co-mutations, especially dnmt3a, reduce remission rates in npm1-mutated aml.

Key Points

  • Assess the prognostic impact of co-occurring mutations in patients with NPM1-mutated acute myeloid leukemia (AML).
  • Retrospective review of adult AML patients diagnosed at the University of Kentucky Markey Cancer Center.
  • Co-mutation analysis performed using a 97-gene next-generation sequencing panel.
  • Treatment response assessed per ELN 2022 criteria, with survival analyses conducted using Kaplan–Meier.
  • Among 457 patients, 104 had NPM1 mutations; 79% achieved complete remission/CR with incomplete hematologic recovery.
  • Higher co-mutation burden was linked to lower odds of achieving remission and poorer RFS and OS.
  • Specific mutations in ASXL1 and TET2 were associated with significantly worse outcomes.

Cite This Study

Safdar et al. (2025) studied this question.

synapsesocial.com/papers/69362f6e4fa91c937236e0aahttps://doi.org/10.1182/blood-2025-1729
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Co-mutation landscape and its prognostic impact on newly diagnosed adult patients with <i>NPM1</i> mutated de novo acute myeloid leukemia.2024
  2. 2Prognostic covariates associated with outcomes in patients with <i>NPM1</i>-mutated acute myeloid leukemia2025 · 3 citations
  3. 3Prognostic Value of Molecular and Clinical Features in Patients with NPM1 Gene Mutation in Acute Myeloid Leukemia.2025 · 1 citations
  4. 4RAS mutations negate the favorable impact of NPM1 in older patients with newly diagnosed Acute Myeloid Leukemia treated with ven/HMA2025 · 1 citations
  5. 5Co-mutation signatures are age-dependent and impact the prognosis in &lt;i&gt;NPM1&lt;/i&gt;-mutated acute myeloid leukemia: a PETHEMA multicenter study2026