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Pre-leukemic evolution of hematopoietic stem cells: the importance of early mutations in leukemogenesis

Leukemia volume 28, pages 2276–2282 (2014)Cite this article

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Abstract

Cancer has been shown to result from the sequential acquisition of genetic alterations in a single lineage of cells. In leukemia, increasing evidence has supported the idea that this accumulation of mutations occurs in self-renewing hematopoietic stem cells (HSCs). These HSCs containing some, but not all, leukemia-specific mutations have been termed as pre-leukemic. Multiple recent studies have sought to understand these pre-leukemic HSCs and determine to what extent they contribute to leukemogenesis. These studies have elucidated patterns in mutation acquisition in leukemia, demonstrated resistance of pre-leukemic cells to standard induction chemotherapy and identified these pre-leukemic cells as a putative reservoir for the generation of relapsed disease. When combined with decades of research on clonal evolution in leukemia, mouse models of leukemogenesis, and recent massively parallel sequencing-based studies of primary patient leukemia, studies of pre-leukemic HSCs begin to piece together the evolutionary puzzle of leukemogenesis. These results have broad implications for leukemia treatment, targeted therapies, minimal residual disease monitoring and early detection screening.

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Acknowledgements

M.R.C.Z. is supported by the Stanford University Smith Fellowship, the NSF GRFP, and the NIH F31 Pre-doctoral fellowship (F31CA180659). R.M. holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund and is a New York Stem Cell Foundation Robertson Investigator.

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  1. Program in Cancer Biology, Stanford Cancer Institute, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center, Stanford, CA, USA

    M R Corces-Zimmerman & R Majeti

  2. Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

    R Majeti

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Correspondence to R Majeti.

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Corces-Zimmerman, M., Majeti, R. Pre-leukemic evolution of hematopoietic stem cells: the importance of early mutations in leukemogenesis. Leukemia 28, 2276–2282 (2014). https://doi.org/10.1038/leu.2014.211

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