Does immune destruction drive all forms of bone marrow failure?
editorial · Level V
Where this comes from
- Record sourced from PubMed, PMID 35912855.
- Also identified by DOI 10.1172/JCI161288 and PMC identifier 9337821.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Current paradigms of bone marrow failure (BMF) pathophysiology suggest that immune-mediated destruction of hematopoietic stem and progenitor cells (HSPCs) drives acquired aplastic anemia. In contrast, loss of HSPCs due to senescence and/or apoptosis causes BMF in inherited BMF syndromes. In this issue of the JCI, Casado and colleagues challenge this dichotomous conception by demonstrating that NK cell-dependent, immune-mediated hematopoietic suppression and HSPC clearance drive BMF in Fanconi anemia (FA). They show that genotoxic stress upregulates natural killer group 2 member D ligands (NKG2D-L) on FA HSPCs leading to NK cell cytotoxicity through NKG2D receptor activation. Inhibition of NKG2D-NKG2D-L interactions enhanced FA HSPC clonogenic potential and improved cytopenias in vivo. These results provide alternative targets for the development of immunosuppressive therapies to reduce HSPC loss and mitigate the risk of hematologic malignancies in FA.
Medical subject headings
- Anemia, Aplastic
- Fanconi Anemia