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 gene, which 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 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.
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August 29, 2024
Emerging genetic technologies informing personalized medicine in Shwachman-Diamond syndrome and other inherited BMF disorders
Alyssa H. Cull,
Alyssa H. Cull
1Department of Biology, Centre for Blood Research, York Biomedical Research Institute, University of York, York, United Kingdom
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David G. Kent,
David G. Kent
1Department of Biology, Centre for Blood Research, York Biomedical Research Institute, University of York, York, United Kingdom
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Alan J. Warren
Alan J. Warren
2Cambridge Institute for Medical Research, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom
3Wellcome Trust-Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom
4Department of Hematology, School of Clinical Medicine, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom
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Blood (2024) 144 (9): 931–939.
Article history
Submitted:
April 2, 2024
Accepted:
June 11, 2024
First Edition:
June 21, 2024
Citation
Alyssa H. Cull, David G. Kent, Alan J. Warren; Emerging genetic technologies informing personalized medicine in Shwachman-Diamond syndrome and other inherited BMF disorders. Blood 2024; 144 (9): 931–939. doi: https://doi.org/10.1182/blood.2023019986
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August 29 2024
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