Detection of MEN1 resistance mutations in cell-free DNA from acute leukemia patients treated with menin inhibitors - Report - MDSpire

Detection of MEN1 resistance mutations in cell-free DNA from acute leukemia patients treated with menin inhibitors

  • By

  • Neerav Shukla

  • Karmelina Charalambous

  • Shanita Li

  • Kaitlyn H. Ko

  • Hilary Casanova

  • Eric Buehler

  • Cassidy Cobbs

  • Ruchi Patel

  • Angela Rose Brannon

  • Mark D. Ewalt

  • Maria Luisa Sulis

  • William L. Carroll

  • Maria E. Arcila

  • Neeman Mohibullah

  • Michael Berger

  • Ross L. Levine

  • Eytan M. Stein

  • Ronak Shah

  • Sheng F. Cai

  • June 16, 2026

  • 0 min

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Identification of MEN1 Resistance Mutations in Circulating Cell-Free DNA

Overview

This study evaluates the feasibility of detecting MEN1 resistance mutations in acute leukemia patients using a novel NGS assay on plasma-derived cell-free DNA.

Background

Menin inhibitors have been approved for treating acute leukemias associated with KMT2A rearrangements and NPM1 mutations. However, the emergence of resistance mutations, particularly in the MEN1 gene, poses a challenge to treatment efficacy. Current detection methods rely on invasive bone marrow aspirates, highlighting the need for alternative, less invasive monitoring techniques.

Data Highlights

No numerical data or trial data provided in the source material.

Key Findings

  • MEN1 mutations are a recurrent mechanism of resistance to menin inhibitors in acute leukemia.
  • The MSK-ACCESS MEN1 assay was developed to detect MEN1 mutations from plasma-derived cfDNA.
  • Concordance between MSK-ACCESS MEN1 and marrow-based MSK-IMPACT Heme assays was high, with a Pearson correlation coefficient of 0.979.
  • Plasma cfDNA analysis may allow for the detection of MEN1 mutations even in cases of minimal or absent circulating disease.
  • This approach may facilitate serial monitoring of resistance mutations.

Clinical Implications

The use of plasma-derived cfDNA for detecting MEN1 resistance mutations could enhance the ability to monitor treatment response in acute leukemia patients. This method may be particularly beneficial in pediatric populations where bone marrow aspiration is more challenging.

Conclusion

The study demonstrates the feasibility of using cfDNA analysis to detect MEN1 resistance mutations.

Related Resources & Content

  1. Blood Cancer Journal, 2023 -- Enhancing the Efficacy of Menin Inhibitors in AML with MLL1-r or Mutant NPM1 by Targeting Epigenetic Co-Dependencies
  2. Blood Cancer Journal, 2022 -- Single-Cell Analysis of Hematopoietic Differentiation in NPM1-Mutated Acute Myeloid Leukemia
  3. Blood Cancer Journal, 2021 -- Combination Therapies Utilizing Menin Inhibitors Show Efficacy in AML with MLL Rearrangements or NPM1c Mutations
  4. Menin inhibitors in the treatment of acute myeloid leukemia | Blood | American Society of Hematology
  5. MEN1 mutations mediate clinical resistance to Menin inhibition - PMC
  6. Blood Cancer Journal — Characterization of Targeted T-cell Responses and T-cell Receptor Specificity for Shared Neoantigens in Acute Myeloid Leukemia
  7. Menin inhibitors in the treatment of acute myeloid leukemia | Blood | American Society of Hematology
  8. Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101) - PubMed
  9. MEN1 mutations mediate clinical resistance to Menin inhibition - PMC

Original Source(s)

Detection of MEN1 resistance mutations in cell-free DNA from acute leukemia patients treated with menin inhibitors

  • by Neerav Shukla, Karmelina Charalambous, Shanita Li, Kaitlyn H. Ko, Hilary Casanova, Eric Buehler, Cassidy Cobbs, Ruchi Patel, Angela Rose Brannon, Mark D. Ewalt, Maria Luisa Sulis, William L. Carroll, Maria E. Arcila, Neeman Mohibullah, Michael Berger, Ross L. Levine, Eytan M. Stein, Ronak Shah, Sheng F. Cai

  • June 16, 2026

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