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Cancer

Inflammation drives pressure on TP53 mutant clones in myeloproliferative neoplasms

Nature Genetics volume 55, pages 1432–1434 (2023)Cite this article

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Transformation of a myeloproliferative neoplasm to a secondary acute myeloid leukemia is rare but devastating. Single-cell, multi-omic characterization of hematopoietic stem and progenitor cells now shows the role of inflammation in transformation driven by mutations in TP53, with effects on the mutant clone but also non-mutant counterparts.

Myeloproliferative neoplasms (MPNs) are hematological disorders that are driven by mutated hematopoietic stem cells. These disorders are characterized by excessive production of erythroid cells (in polycythemia vera), platelets (in essential thrombocythemia) or white blood cells (in primary myelofibrosis). A subset of MPNs progress to secondary acute myeloid leukemia (sAML), which resists treatments used for de novo AML and is associated with a dismal outcome1,2. Secondary AML also displays a mutational profile that is distinct from that of de novo AML, and should be considered a distinct disease entity2.

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Fig. 1: Genetic evolution of HSPCs during leukemic transformation driven by TP53 mutations.

References

  1. Rampal, R. et al. Proc. Natl Acad. Sci. USA 111, E5401–E5410 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dunbar, A. J., Rampal, R. K. & Levine, R. Blood 136, 61–70 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lundberg, P. et al. Blood 123, 2220–2228 (2014).

    Article  CAS  PubMed  Google Scholar 

  4. Kubesova, B. et al. Leukemia 32, 450–461 (2018).

    Article  CAS  PubMed  Google Scholar 

  5. Bernard, E. et al. Nat. Med. 26, 1549–1556 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Luque Paz, D. et al. Blood Adv. 4, 4887–4897 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Rodriguez-Meira, A. et al. Nat. Genet. https://doi.org/10.1038/s41588-023-01480-1 (2023).

    Article  PubMed  Google Scholar 

  8. Rodriguez-Meira, A. et al. Mol. Cell 73, 1292–1305.e8 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mesa, R. A. et al. Blood 105, 973–977 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Walter, D. et al. Nature 520, 549–552 (2015).

    Article  CAS  PubMed  Google Scholar 

  11. Tefferi, A. Am. J. Hematol. 96, 145–162 (2021).

    Article  CAS  PubMed  Google Scholar 

  12. Stubbins, R. J., Platzbecker, U. & Karsan, A. Blood 140, 1067–1074 (2022).

    Article  CAS  PubMed  Google Scholar 

  13. Nam, A. S. et al. Nature 571, 355–360 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Van Egeren, D. et al. Cell Stem Cell 28, 514–523.e9 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Myers, R. M. et al. Preprint at bioRxiv https://doi.org/10.1101/2022.05.11.491515 (2022).

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Authors and Affiliations

  1. Oncode Institute, Erasmus MC, Rotterdam, The Netherlands

    Adam Benabid & Rebekka K. Schneider

  2. Department of Cell and Tumor Biology; Medical Faculty, RWTH Aachen University, Aachen, Germany

    Adam Benabid & Rebekka K. Schneider

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  1. Adam Benabid
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  2. Rebekka K. Schneider
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Correspondence to Rebekka K. Schneider.

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Benabid, A., Schneider, R.K. Inflammation drives pressure on TP53 mutant clones in myeloproliferative neoplasms. Nat Genet 55, 1432–1434 (2023). https://doi.org/10.1038/s41588-023-01479-8

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