ArticleThe Journal of clinical investigation2022
Mutant Samd9l expression impairs hematopoiesis and induces bone marrow failure in mice.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- A unified multimodal single-cell framework reveals a discrete state model of hematopoiesis in mice.Nature immunology · 2025Article
- Normal Immune Function in a Newborn With Early Identification of aClinical case reports · 2025Article
- Genomic landscape and clonal architecture in pediatric myeloid neoplasms with chromosome 7 deletions.Blood neoplasia · 2025Article
- SAMD9 senses cytosolic double-stranded nucleic acids in epithelial and mesenchymal cells to induce antiviral immunity.Nature communications · 2025Article
- Review
- Non-Malignant Granulocyte and Monocyte Disorders: An Update.British journal of biomedical science · 2025Review
- Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications.Annual review of pathology · 2025Review
- Germline variants in acquired aplastic anemia: current knowledge and future perspectives.Haematologica · 2024Review
- Overexpression of human SAMD9 inhibits protein translation and alters MYC signaling resulting in cell cycle arrest.Experimental hematology · 2024Article
- Malignant progression of preleukemic disorders.Blood · 2024Review
- Functional characterization of cooperating MGA mutations in RUNX1::RUNX1T1 acute myeloid leukemia.Leukemia · 2024Article
- 5G2 mutant mice model loss of a commonly deleted segment of chromosome 7q22 in myeloid malignancies.Leukemia · 2024Article
- ETV6 represses inflammatory response genes and regulates HSPC function during stress hematopoiesis in mice.Blood advances · 2023Article
- The Molecular and Genetic Mechanisms of Inherited Bone Marrow Failure Syndromes: The Role of Inflammatory Cytokines in Their Pathogenesis.Biomolecules · 2023Review
- Sticky, Adaptable, and Many-sided: SAM protein versatility in normal and pathological hematopoietic states.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- Inflammation fuels bone marrow exhaustion caused by Samd9l mutation.The Journal of clinical investigation · 2022Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
SAMD9 and SAMD9L germline mutations have recently emerged as a new class of predispositions to pediatric myeloid neoplasms. Patients commonly have impaired hematopoiesis, hypocellular marrows, and a greater risk of developing clonal chromosome 7 deletions leading to MDS and AML. We recently demonstrated that expressing SAMD9 or SAMD9L mutations in hematopoietic cells suppresses their proliferation and induces cell death. Here, we generated a mouse model that conditionally expresses mutant Samd9l to assess the in vivo impact on hematopoiesis. Using a range of in vivo and ex vivo assays, we showed that cells with heterozygous Samd9l mutations have impaired stemness relative to wild-type counterparts, which was exacerbated by inflammatory stimuli, and ultimately led to bone marrow hypocellularity. Genomic and phenotypic analyses recapitulated many of the hematopoietic cellular phenotypes observed in patients with SAMD9 or SAMD9L mutations, including lymphopenia, and pinpointed TGF-β as a potential targetable pathway. Further, we observed nonrandom genetic deletion of the mutant Samd9l locus on mouse chromosome 6, mimicking chromosome 7 deletions observed in patients. Collectively, our study has enhanced our understanding of mutant Samd9l hematopoietic phenotypes, emphasized the synergistic role of inflammation in exaggerating the associated hematopoietic defects, and provided insights into potential therapeutic options for patients.
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Registered trials
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.