# Decoding Leukemic Stem Cells in AML: From Identification to Targeted Eradication

## TL;DR

This review explores how leukemic stem cells in AML resist treatment and how they can be targeted for eradication.

## Contribution

The paper provides a comprehensive synthesis of recent advances in understanding and targeting leukemic stem cells in AML.

## Key findings

- Leukemic stem cells differ from normal stem cells in function and phenotype.
- Epigenetic and metabolic programs support LSC survival during chemotherapy.
- Therapeutic strategies targeting LSCs include antibodies, apoptosis inhibitors, and epigenetic agents.

## Abstract

Acute myeloid leukemia (AML) continues to pose significant therapeutic challenges, with high relapse rates driven largely by leukemic stem cells (LSCs), a rare, therapy-resistant population with self-renewal capacity, niche adaptation, and the ability to re-initiate disease. In this state-of-the-art review, we synthesize recent advances in LSC biology, addressing (i) how LSCs differ functionally and phenotypically from normal hematopoietic stem cells (HSCs), (ii) practical approaches for LSC quantification using multiparameter flow cytometry and LSC-enriched marker panels, (iii) the dysregulated signaling, metabolic and epigenetic programs that enable LSC persistence under chemotherapy and contribute to measurable residual disease, and (iv) current therapeutic strategies targeting LSC eradication, including antibody-based therapies, apoptosis and metabolic inhibitors, and emerging epigenetic agents. We also examine the key translational barriers, particularly antigen overlap with normal progenitors, microenvironmental protection, and the need for assay harmonization, while proposing a practical framework for integrating LSC assessment into risk stratification and therapeutic development.