The ribosomopathy Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive inherited bone marrow failure syndrome (IBMFS) caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene, that is associated with an increased risk of myeloid malignancy. Tracking how hematopoietic stem cell (HSC) clonal dynamics change over time, assessing whether somatic genetic rescue mechanisms affect these dynamics, and mapping out when leukemic driver mutations are acquired is important to understand which individuals with SDS may go on to develop leukemia. In this review, we will discuss how new technologies that allow researchers to map mutations at the level of single HSC clones are generating important insights into genetic rescue mechanisms and their relative risk for driving evolution to leukemia, and how these data can inform the future development of personalized medicine approaches in SDS and other IBMFSs.
Research Article|
June 21, 2024
Emerging genetic technologies informing personalized medicine in SDS and other inherited bone marrow failure disorders
Alyssa H. Cull,
Alyssa H. Cull
University of York, York, United Kingdom
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David G. Kent,
University of York, York, United Kingdom
* Corresponding Author; email: david.kent@york.ac.uk
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Alan J. Warren
Alan J. Warren
University of Cambridge, Cambridge, United Kingdom
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Blood blood.2023019986.
Article history
Submitted:
April 2, 2024
Revision Received:
June 11, 2024
Accepted:
June 11, 2024
Citation
Alyssa H. Cull, David G. Kent, Alan J. Warren; Emerging genetic technologies informing personalized medicine in SDS and other inherited bone marrow failure disorders. Blood 2024; blood.2023019986. doi: https://doi.org/10.1182/blood.2023019986
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