The hematopoietic saga of clonality in sickle cell disease
Aaron J. Stonestrom, Ross L. Levine
Aaron J. Stonestrom, Ross L. Levine
Published March 1, 2022
Citation Information: J Clin Invest. 2022;132(5):e158251. https://doi.org/10.1172/JCI158251.
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The hematopoietic saga of clonality in sickle cell disease

Abstract

Sickle cell disease (SCD) is associated with an increased risk of vascular-occlusive events and of leukemia. Clonal hematopoiesis (CH) may increase both risks. In turn, physiologic abnormalities in SCD may modify the incidence and/or distribution of genetic alterations in CH. In a recent issue of the JCI, Liggett et al. found no difference in CH rate between individuals with versus without SCD. Here we contextualize this report and discuss the complex interplay between CH and SCD with particular attention to consequences for emerging gene therapies. We further consider the limitations in our current understanding of these topics that must be addressed in order to optimize therapeutic strategies for SCD.

Authors

Aaron J. Stonestrom, Ross L. Levine

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Figure 1

Clonal dynamics in sickle cell disease and its therapy.

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Clonal dynamics in sickle cell disease and its therapy. (A) High-output ...
(A) High-output erythropoiesis and the inflammatory state of sickle cell disease may create an environment that favors hematopoietic clones with specific mutations. Mutant hematopoietic clones may also have increased potential to trigger sickling and inflammation. (B) Hematopoietic stem cell harvest and expansion may cause a bottleneck in the hematopoietic progenitor population followed by an expansion phase, both of which may favor mutant cells. This expanded proportion of mutant stem cells may place patients at high risk of leukemic transformation.