Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis

S. Avagyan; J. E. Henninger; W. P. Mannherz; M. Mistry; J. Yoon; S. Yang; M. C. Weber; J. L. Moore; L. I. Zon

doi:10.1126/science.aba9304

journal article Nov 05, 2021

Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis

S. Avagyan J. E. Henninger

W. P. Mannherz

M. Mistry

J. Yoon S. Yang

M. C. Weber J. L. Moore

L. I. Zon

Science Vol. 374 No. 6568 pp. 768-772 · American Association for the Advancement of Science (AAAS)

View at Publisher Save 10.1126/science.aba9304

Abstract

Colorful clones in the blood

Stem cells in regenerating tissues such as the blood can acquire mutations that enable a growth advantage, increasing the chance of developing cancer. It is unclear how such diverse mutations promote clonal fitness. Avagyan
et al
. generated a platform in zebrafish to label clones with unique hues while inducing mutations in genes implicated in human blood disorders. Mutations in some genes caused clones to expand over time, resulting in clonal dominance. Progenitors in the dominant clone expressed anti-inflammatory factors to resist the inflammatory environment produced by their own mature progeny, leading to a self-perpetuating cycle promoting clonal fitness. Targeting these resistance pathways may be used to abate clonal hematopoiesis and prevent its associated pathology. —BAP

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Citations

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References

Details

Published: Nov 05, 2021
Vol/Issue: 374(6568)
Pages: 768-772

Authors

S

S. Avagyan

Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, USA.

J

J. E. Henninger

Whitehead Institute for Biomedical Research, Cambridge, MA, USA.

W

W. P. Mannherz

Harvard Medical School, Boston, MA, USA.

M

M. Mistry

Harvard Chan Bioinformatics Core, Boston, MA, USA.

J

J. Yoon

Harvard Chan Bioinformatics Core, Boston, MA, USA.

S

S. Yang

Boston Children’s Hospital, Boston, MA, USA.

M

M. C. Weber

Boston Children’s Hospital, Boston, MA, USA.

J

J. L. Moore

Boston Children’s Hospital, Boston, MA, USA.

L

L. I. Zon

Boston Children’s Hospital, Boston, MA, USA.; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA.

Cite This Article

S. Avagyan, J. E. Henninger, W. P. Mannherz, et al. (2021). Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis. Science, 374(6568), 768-772. https://doi.org/10.1126/science.aba9304

Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis

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