REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
This article is part of the Research TopicDiagnostic, Prognostic and Predictive Markers in LeukemiaView all 13 articles
Flow Cytometric Evaluation of Leukemic Stem Cells in Acute Myeloid Leukemia: Ready for Clinical Diagnostics?
Provisionally accepted
- Pathology, New York University Grossman School of Medicine, New York, United States
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The assessment of measurable residual disease (MRD) plays a critical role in acute myeloid leukemia (AML) treatment response evaluation and prognosis. However, current AML MRD detection by flow cytometry (FC) is limited in sensitivity due to immunophenotypic variability, similarities to normal hematopoietic stem/progenitor cells, and the lack of stable leukemia-associated immunophenotypes. A significant proportion of AML patients classified as MRD-negative by FC eventually relapse, likely due to the persistence of therapy-resistant leukemic stem cells (LSCs) that are not sensitively detected by routine clinical flow panels. Flow cytometry panels designed to detect LSC antigens, while promising, face challenges like immunophenotypic heterogeneity across AML subtypes, lack of standardized marker panels across laboratories, and limited validation. Here, we summarize the current state of FC-based LSC detection in AML, discussing commonly used markers, immunophenotypic variability, assay setup challenges, and we review recent clinical studies on LSCs measurement, outlining their main findings and implications for prognosis and MRD integration. We also consider advances in spectral flow cytometry for improved LSC detection.
Keywords: AML - acute myeloid leukemia, LSC - leukemic stem cells, flow cyometry, MRD - measurable residual disease, Therapeutic targeting biomarkers
Received: 14 Oct 2025; Accepted: 14 Nov 2025.
Copyright: © 2025 Youssef and Park. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mariam Youssef, mariam.youssef@nyulangone.org
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