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Acute Myeloid Leukemia Stem Cells: Origin, Characteristics, and Clinical Implications

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Abstract

The stem cells of acute myeloid leukemia (AML) are the malignancy initiating cells whose survival ultimately drives growth of these lethal diseases. Here we review leukemia stem cell (LSC) biology, particularly as it relates to the very heterogeneous nature of AML and to its high disease relapse rate. Leukemia ontogeny is presented, and the defining functional and phenotypic features of LSCs are explored. Surface and metabolic phenotypes of these cells are described, particularly those that allow distinction from features of normal hematopoietic stem cells (HSCs). Opportunities for use of this information for improving therapy for this challenging group of diseases is highlighted, and we explore the clinical needs which may be addressed by emerging LSC data. Finally, we discuss current gaps in the scientific understanding of LSCs.

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Funding

This work is supported by the NIH award 2P01CA171983-06A1 and funds from the Kenneth Noel Memorial Foundation – to Dr. Claxton.

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Authors and Affiliations

  1. Penn State College of Medicine, Hershey, PA, USA

    Nathaniel A. Long

  2. Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA, USA

    Upendarrao Golla, Arati Sharma & David F. Claxton

  3. Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA, USA

    Upendarrao Golla, Arati Sharma & David F. Claxton

  4. Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA, USA

    Arati Sharma

  5. Division of Hematology and Oncology, Penn State Cancer Institute, Cancer Institute, Next-Generation Therapies, 500 University, Hershey, PA, 17033, USA

    David F. Claxton

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NL and DC researched the literature and wrote the manuscript. UG prepared figures and revised the manuscript. AS revised and refined the manuscript.

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Correspondence to David F. Claxton.

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Long, N.A., Golla, U., Sharma, A. et al. Acute Myeloid Leukemia Stem Cells: Origin, Characteristics, and Clinical Implications. Stem Cell Rev and Rep 18, 1211–1226 (2022). https://doi.org/10.1007/s12015-021-10308-6

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