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‘CHIP’ping away at clonal hematopoiesis

Leukemia volume 30, pages 1633–1635 (2016)Cite this article

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There is emerging evidence that treatment with myeloablative chemotherapy provides a competitive fitness advantage to HSPCs carrying certain CHIP-associated mutations. We observed that TP53 mutations present in the dominant clone at the time of therapy-related AML (t-AML) diagnosis were detectable at extremely low levels in hematopoietic cells years before cytotoxic chemotherapy exposure.12 This suggests that TP53 mutant cells may be relatively resistant to chemotherapy compared with non-mutant cells (Figure 2). Indeed, we showed that Tp53 mutant cells expand relative to wild-type cells following cytotoxic chemotherapy exposure using an in vivo mouse model.12 The data suggests that rare HSPCs carrying age-related TP53 mutations are resistant to chemotherapy and expand preferentially after treatment. Similarly, our group recently reported the preferential expansion of clonal hematopoietic cells following induction chemotherapy for AML (that is, ‘rising clones’).13 These non-leukemic hematopoietic cells harbored mutations commonly associated with CHIP that were not present in the AML cells, indicating that these mutations identify distinct non-leukemic cells that are different from ‘pre-leukemic’ cells that can persist during AML remission.14, 15

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Figure 1
Figure 2

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Acknowledgements

This work was supported by a Leukemia and Lymphoma Society Scholar Award (MJW). We are grateful to Tim Ley for helpful scientific discussions.

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  1. Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA

    D C Link & M J Walter

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Correspondence to M J Walter.

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Link, D., Walter, M. ‘CHIP’ping away at clonal hematopoiesis. Leukemia 30, 1633–1635 (2016). https://doi.org/10.1038/leu.2016.130

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