# High-Throughput Proteomic Profiling to Evaluate Differentiation Syndrome With Menin Inhibition

## TL;DR

This study uses a new high-throughput proteomic method to track inflammatory proteins in children with AML treated with menin inhibitors, aiming to better understand and manage a dangerous side effect called differentiation syndrome.

## Contribution

The novel NULISAseq technology enables ultrasensitive detection of soluble inflammatory proteins in AML patients treated with menin inhibitors.

## Key findings

- NULISAseq identified dynamic changes in soluble proteins during menin inhibitor treatment.
- The method can distinguish differentiation syndrome biomarkers from leukemia-related proteins.
- Proteomic profiling may improve outcomes by guiding treatment response in AML patients.

## Abstract

High-throughput proteomic profiling provides a comprehensive analysis of systemic cancer effects and tumor microenvironment interactions. Characterizing soluble proteins driving inflammation in acute myeloid leukemia (AML) offers insight into inflammatory diseases like differentiation syndrome related to AML therapies like menin inhibitors. We present our application of nucleic acid-linked immuno-sandwich assay, a novel technology leveraging next-generation sequencing for high-throughput, ultrasensitive characterization of secreted inflammatory proteins in plasma or serum. Here, we report its use to identify dynamic soluble protein changes during treatment and at the time of suspected differentiation syndrome in pediatric AML patients treated with the menin inhibitor revumenib (NCT04065399 and NCT05360160).

•Menin inhibitors are novel targeted therapies for rare-mutated acute myeloid leukemia.•Differentiation syndrome and cytokine imbalance related to menin inhibition may be lethal.•NULISAseq analysis of protein markers of differentiation syndrome may improve outcomes.•NULISAseq may distinguish differentiation biomarkers from leukemia to guide treatment response.

Menin inhibitors are novel targeted therapies for rare-mutated acute myeloid leukemia.

Differentiation syndrome and cytokine imbalance related to menin inhibition may be lethal.

NULISAseq analysis of protein markers of differentiation syndrome may improve outcomes.

NULISAseq may distinguish differentiation biomarkers from leukemia to guide treatment response.

High-throughput proteomics using NULISAseq enables ultrasensitive detection of inflammatory proteins in acute myeloid leukemia. This NGS-based assay was utilized to identify dynamic protein changes during treatment and suspected differentiation syndrome in pediatric patients with acute myeloid leukemia receiving the menin inhibitor revumenib.