Related Experiment Video

Updated: Jan 24, 2026

VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma

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Single-cell proteogenomic analysis of clonal evolution in PDX models of AML treated with IDH inhibitors

Alex C H Liu1,2, Severine Cathelin1, Dhanoop Manikoth Ayyathan1

  • 1Princess Margaret Cancer Centre, Toronto, ON, Canada.

Blood Neoplasia
|January 23, 2026
PubMed

Insights

Single-cell analysis of acute myeloid leukemia (AML) in patient-derived xenografts reveals how IDH inhibitors impact clonal evolution. This study identifies resistance mechanisms and informs new therapeutic strategies against AML.

Area of Science:

  • Hematology
  • Molecular Biology
  • Cancer Research

Background:

  • Clonal heterogeneity in acute myeloid leukemia (AML) contributes to treatment resistance.
  • Understanding clonal evolution under therapeutic pressure is crucial for overcoming drug resistance.

Purpose of the Study:

  • To monitor clonal evolution and differentiation in IDH-mutated AML using patient-derived xenografts (PDX) treated with IDH inhibitors.
  • To investigate drug resistance mechanisms and inform therapeutic strategies through single-cell proteogenomic analysis.

Main Methods:

  • Employed single-cell proteogenomic analysis in IDH-mutated AML patient-derived xenografts (PDX).
  • Utilized mixed PDX models with coengrafted leukemic samples and single-cell DNA sequencing.
  • Tracked clonal evolution under selective pressure from IDH inhibitors and combination therapies.

Main Results:

  • Identified an association between WT1 mutations and resistance to ivosidenib monotherapy in IDH1-mutated AML.
  • Observed antagonism between ivosidenib and enasidenib when tested in IDH1-mutated cells.
  • Demonstrated the utility of single-cell proteogenomic analysis in PDX models for studying drug resistance.

Conclusions:

  • Single-cell proteogenomic analysis of PDX models provides insights into AML clonal evolution and drug resistance.
  • Findings illuminate resistance mechanisms to IDH inhibitors and inform the development of effective therapeutic strategies.

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