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The variety of leukemic stem cells in myeloid malignancy

Oncogene volume 33, pages 3091–3098 (2014)Cite this article

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Abstract

Human acute myeloid leukemias (AMLs) are sustained by leukemic stem cells (LSCs) that generate through aberrant differentiation the blast cells that make up the bulk of the malignant clone. LSCs were first identified as rare cells with an immunophenotype shared with normal hematopoietic stem cells (HSCs). However, refinements of xenotransplantation assays, alternative methods of quantitation and syngeneic murine models have all led to an appreciation that LSCs display marked variability in frequency, immunophenotype and differentiation potential, both between and even within leukemias. Insights from next-generation sequencing efforts have dramatically extended understanding of the mutational landscape and clonal organization of AML and have added an additional layer of complexity to the biology of LSCs: a requirement to consider the effect of the various recurrently occurring genetic lesions in AML on the initiation and maintenance of leukemic subclones. Despite these advances, cure rates in AML remain substantially unchanged in recent years. A renewed focus on the biological properties of chemotherapy-resistant LSCs, a cellular entity of prime clinical importance, will be required to develop additional therapeutic strategies to enhance patient outcomes.

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Acknowledgements

We apologize to the many clinicians and scientists who have contributed to this field whose work we were unable to cite because of space constraints. DW and BG are recipients of Leukaemia and Lymphoma Research Clinical Training Fellowships. TS is supported by Cancer Research UK grant number C5759/A12328.

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  1. Cancer Research UK Leukaemia Biology Laboratory, Paterson Institute for Cancer Research, The University of Manchester, Manchester, UK

    D H Wiseman, B F Greystoke & T C P Somervaille

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Wiseman, D., Greystoke, B. & Somervaille, T. The variety of leukemic stem cells in myeloid malignancy. Oncogene 33, 3091–3098 (2014). https://doi.org/10.1038/onc.2013.269

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