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The secrets of the bone marrow niche: Metabolic priming for AML

Nature Medicine volume 18, pages 865–867 (2012)Cite this article

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Cancer survivors have recovered from a brush with death, but their battle is often not over. The rigors of their initial bout with the disease predispose them to a second round, often with a more lethal foe in the form of secondary acute myeloid leukemia (AML). The risk of these events is high after particular types of cancer therapy and in people with 'premalignant' myleodysplastic syndrome (MDS) and myeloproliferative disorder, indicating that patient groups can therefore be assessed for markers that may predict for the fight to come. Approximately 15% of all AML develops secondary to cancer chemotherapy with alkylating agents or topoisomerase inhibitors1. Alkylating agents function by adding alkyl groups to DNA, causing DNA damage. Ideally, this would result in cancer cell death; however, it can also lead to incorrect chromosome segregation in cancer cells that escape apoptosis and frequent loss of portions of chromosomes 5q and 7q (ref. 2). DNA topoisomerase inhibitors result in DNA cleavage and chromosome breakage, leading to apoptosis. However, in cancer cells where this process does not go as planned, translocations, often involving the mixed-lineage leukemia gene (MLL), can lead to secondary AML3.

Historically, secondary AML was thought to be essentially untreatable. However, it is now clear that it comprises a heterogeneous group of disorders, and prognosis and choice of treatment depends upon the cytogenetic and molecular changes found in the particular case under consideration4. The study of those at risk for secondary AML provides a unique opportunity for capturing the molecular events driving clonal dominance that eventuates in leukemia.

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Authors and Affiliations

  1. Department of Stem Cell and Regenerative Biology, Rushdia Z. Yusuf, Ying-Hua Wang and David T. Scadden are at the Massachusetts General Hospital Center for Regenerative Medicine and Cancer Center, Harvard Stem Cell Institute, Harvard University, Boston, Massachusetts, USA.,

    Rushdia Z Yusuf, Ying-Hua Wang & David T Scadden

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  1. Rushdia Z Yusuf
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  2. Ying-Hua Wang
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  3. David T Scadden
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Correspondence to David T Scadden.

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Competing interests

D.T.S. is a consultant to and stockholder of Fate Therapeutics.

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Yusuf, R., Wang, YH. & Scadden, D. The secrets of the bone marrow niche: Metabolic priming for AML. Nat Med 18, 865–867 (2012). https://doi.org/10.1038/nm.2831

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