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Stem cell divisions and cancer

Leukemia volume 29, page 1959 (2015)Cite this article

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The intriguing work by Tomasetti and Vogelstein1 implicates number of stem cell divisions in cancer risk. The authors proposed ‘the lifetime risk of cancers on many different types is strongly correlated (0.81) with total number of divisions of normal self-renewing cells maintaining that tissues homeostasis.’ Their results suggested that ‘only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions.’ They focused on the ‘extreme variation in cancer incidence across different tissues’ and identified 31 tissue types to assess stem cell numbers and proliferative rate. They further clustered cancer types into deterministic or replicative. Deterministic referred to cancers caused by deterministic factors ‘such as environmental mutagens or hereditary predispositions.’ Replicative referred to cancers related to ‘errors during DNA replication.’ This, of course, depends entirely on the validity of input data. We recently reported that previous estimates of proliferative rates of bone marrow hematopoietic stem cells are wrong.2 Prior studies suggested primitive bone marrow stem cells were dormant in GO, but we found virtually all primitive bone marrow stem cells are proliferating and the previously defined G0 stem cells rapidly transit cycle in vivo.3 The problem in prior estimates was that most proliferating stem cells were discarded by the standard stem cell purifications.

The bone marrow hematopoietic stem cell is probably the best, most extensively studied stem cell; other stem cell systems are generally poorly defined and determination of their replicative rates borders on the fanciful, including chronic lymphocytic leukemia, Glioblastoma multiforme, head and neck squamous cell carcinoma, lung adenocarcinoma and osteosarcoma. In the latter instance the authors state that ‘stem cells divide every 15 years.’ This is quite extraordinary. Finally, one might consider that every lymphocyte is a potential stem cell when it encounters its antigen. Altogether estimates of stem cell proliferation in all of these cell systems are unreliable.

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  1. Department of Hematology/Oncology, Brown University/Rhode Island Hospital, Providence, RI, USA

    P J Quesenberry & L R Goldberg

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  1. P J Quesenberry
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  2. L R Goldberg
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Correspondence to P J Quesenberry.

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Quesenberry, P., Goldberg, L. Stem cell divisions and cancer. Leukemia 29, 1959 (2015). https://doi.org/10.1038/leu.2015.166

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