Related Experiment Video
Updated: Sep 20, 2025
Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia
Maria Sirenko1, Soobeom Lee2, Zhengxi Sun3
1Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Mutations in Isocitrate Dehydrogenase (IDH) drive acute myeloid leukemia (AML) with distinct cellular phenotypes and treatment responses. Understanding these mutations aids in developing precision medicine for AML patients.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Isocitrate dehydrogenase (IDH) mutations are early drivers in acute myeloid leukemia (AML).
- IDH-mutant AML exhibits complex clonal architecture and cellular heterogeneity, leading to varied clinical outcomes.
- Understanding the cellular phenotypes and molecular programs in IDH-mutant AML is crucial for targeted therapies.
Purpose of the Study:
- To characterize the stem-like and inflammatory phenotype of IDH-mutant AML.
- To identify clone-specific programs associated with co-mutations (NPM1, NRAS, SRSF2).
- To analyze treatment responses and relapse mechanisms in IDH-mutant AML.
Main Methods:
- Integration of single-cell genotyping and transcriptomics.
- Phenotypic and molecular analysis of IDH-mutant AML at diagnosis, during treatment, and at relapse.
- Investigation of pre-leukemic stages.
Main Results:
- IDH-mutant AML displays stem-like and inflammatory characteristics.
- Co-mutations define distinct clone-specific programs and differential treatment responses to IDH inhibitors and chemotherapy.
- Relapse following IDH inhibitor monotherapy is associated with upregulated stemness, inflammation, mitochondrial metabolism, anti-apoptotic factors, and downregulated MHC class II antigen presentation.
- Pre-leukemic stages show upregulated IDH2-associated inflammatory pathways.
Conclusions:
- IDH mutations contribute to a distinct AML phenotype with implications for treatment strategy.
- Clone-specific programs and heterogeneity influence therapeutic outcomes in IDH-mutant AML.
- Detailed phenotyping provides a framework for precision medicine approaches in AML, particularly at relapse.
