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

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  • 1Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

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This study introduces NUcleic acid-Linked Immuno-Sandwich Assay (NULISA) for tracking inflammatory proteins in acute myeloid leukemia (AML). NULISA identified key protein changes during treatment and differentiation syndrome (DS) in pediatric AML patients.

Keywords:
acute myeloid leukemiadifferentiation syndromemenin inhibitorspediatricproteomicsrelapsed refractory AML

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Area of Science:

  • Oncology
  • Immunology
  • Biotechnology

Background:

  • High-throughput proteomic profiling aids in understanding cancer's systemic effects and tumor microenvironment.
  • Inflammatory soluble proteins in acute myeloid leukemia (AML) are crucial for understanding diseases like differentiation syndrome (DS).
  • Menin inhibitors are a therapeutic strategy for AML, but can induce DS.

Purpose of the Study:

  • To apply a novel high-throughput proteomic technology, NULISA, for characterizing secreted inflammatory proteins.
  • To identify dynamic soluble protein changes in pediatric AML patients during treatment with the menin inhibitor revumenib.
  • To detect protein alterations associated with differentiation syndrome (DS) in these patients.

Main Methods:

  • Development and application of NUcleic acid-Linked Immuno-Sandwich Assay (NULISA), a next-generation sequencing (NGS)-based technology.
  • Analysis of plasma or serum samples from pediatric AML patients undergoing treatment with revumenib.
  • Monitoring protein expression profiles during therapy and at the onset of suspected DS.

Main Results:

  • NULISA enabled ultra-sensitive, high-throughput characterization of secreted inflammatory proteins.
  • Dynamic changes in soluble protein levels were identified during revumenib treatment.
  • Specific protein signatures were observed at the time of suspected differentiation syndrome (DS).

Conclusions:

  • NULISA is a powerful tool for dissecting inflammatory mechanisms in AML and related conditions.
  • The study provides insights into the molecular underpinnings of differentiation syndrome (DS) in pediatric AML.
  • This proteomic approach can inform therapeutic monitoring and the development of targeted treatments for AML.