ArticleNature communications2021
Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 168 citations in OpenAlex.
- Csnk1a1 E98 mutations rewire signaling and metabolism in del(5q) myelodysplastic neoplasms.Leukemia · 2026Article
- Genetic influences on haematopoiesis.Nature reviews. Genetics · 2026Review
- Distinct stem cell identities converge into shared erythroid stress in ERCC6L2 disease and Shwachman-Diamond syndrome.HemaSphere · 2026Article
- Article
- Clonal hematopoiesis and its progression to myeloid neoplasms: insights into risk, biology, and therapeutic strategies.Haematologica · 2026Review
- High-resolution single-cell mapping of clonal hematopoiesis and structural variation in aplastic anemia.Nature genetics · 2026Article
- Article
- Functional impact of the eIF6 N106S mutation on ribosome biogenesis in wild type and Shwachman-Diamond syndrome cells.Molecular medicine (Cambridge, Mass.) · 2026Article
- Somatic mutations and clonal evolution in normal tissues and cancer development.Experimental & molecular medicine · 2026Review
- CDK4/6 inhibition mitigates chemotherapy-induced expansion of TP53-mutant clonal hematopoiesis.Nature genetics · 2026Article
- From ribosomopathies to therapeutic targets: ribosomal alterations in pediatric leukemogenesis and tumorigenesis.Frontiers in oncology · 2026Review
- Established and emerging non-cellular therapies in inherited bone marrow failure syndromes.Frontiers in immunology · 2026Review
- Molecular diagnostics 101: how to use genetic tests in classical hematology.Hematology. American Society of Hematology. Education Program · 2025Review
- Global comprehensive transcriptomic and proteomic analyses of murine terminal erythroid differentiation.Global medical genetics · 2025Article
- Beyond Hematologic Malignancies: Colorectal Cancer as a Solid Tumor Manifestation of Inherited Bone Marrow Failure Syndromes.International journal of molecular sciences · 2025Review
- Review
- Genetic Predisposition to Hematologic Malignancies.Cold Spring Harbor perspectives in medicine · 2025Review
- Germline and somatic genetic landscape of pediatric myelodysplastic syndromes.Haematologica · 2025Review
- The TP53 tumor suppressor gene: From molecular biology to clinical investigations.Journal of internal medicine · 2025Review
- Germline genetic variation impacts clonal hematopoiesis landscape and progression to malignancy.Nature genetics · 2025Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
43 authors at 20 institutions in 2 countries.
Funding
Abstract
To understand the mechanisms that mediate germline genetic leukemia predisposition, we studied the inherited ribosomopathy Shwachman-Diamond syndrome (SDS), a bone marrow failure disorder with high risk of myeloid malignancies at an early age. To define the mechanistic basis of clonal hematopoiesis in SDS, we investigate somatic mutations acquired by patients with SDS followed longitudinally. Here we report that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations in EIF6 or TP53. We show that germline SBDS deficiency establishes a fitness constraint that drives selection of somatic clones via two distinct mechanisms with different clinical consequences. EIF6 inactivation mediates a compensatory pathway with limited leukemic potential by ameliorating the underlying SDS ribosome defect and enhancing clone fitness. TP53 mutations define a maladaptive pathway with enhanced leukemic potential by inactivating tumor suppressor checkpoints without correcting the ribosome defect. Subsequent development of leukemia was associated with acquisition of biallelic TP53 alterations. These results mechanistically link leukemia predisposition to germline genetic constraints on cellular fitness, and provide a rational framework for clinical surveillance strategies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.