Related Experiment Video
Updated: May 8, 2026
11:15
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
24.3K
Genotype-immunophenotype relationships in NPM1-mutant AML clonal evolution uncovered by single cell multiomic
Morgan Drucker1, Darren Lee2, Xuan Zhang3
1Division of Hematology/Oncology, Cancer & Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati OH USA.
Biorxiv : the Preprint Server for Biology
|November 28, 2024
Summary
Single cell analysis reveals that Acute myeloid leukemia (AML) clonal architecture is similar at diagnosis and relapse, but mutations increase diversity upon relapse. Genotype-specific relationships guide leukemia cell states during treatment.
Area of Science:
- Hematology
- Cancer Biology
- Genomics
Background:
- Acute myeloid leukemia (AML) is a complex multi-clonal disease.
- Bulk sequencing methods limit the understanding of AML clonal architecture and evolution during therapy.
- Interrogating clonal evolution requires advanced single-cell techniques.
Purpose of the Study:
- To investigate the clonal evolution and genotype-immunophenotype relationships in NPM1-mutant AML.
- To analyze dynamic changes in clonal, transcriptomic, and immunophenotypic profiles during therapy.
Main Methods:
- Simultaneous single-cell molecular profiling and immunophenotyping.
- Analysis of 43 samples from 32 NPM1-mutant AML patients at diagnosis, relapse, and during therapy.
- Longitudinal sampling to track dynamic changes.
Main Results:
- Diagnosis and relapsed AML samples show similar clonal architecture.
- Signaling mutations drive increased clonal diversity at relapse.
- Unique genotype-immunophenotype relationships were identified, suggesting mutation-driven lineage trajectories.
- Dynamic clonal, transcriptomic, and immunophenotypic changes were observed in patients undergoing therapy.
Conclusions:
- Single-cell profiling provides a resolved understanding of leukemic clonal evolution in AML.
- Genotype significantly influences cell state and lineage trajectories in AML.
- Therapy induces dynamic changes in AML clonal and cellular states.
