Recipient-driven metabolic and epigenetic remodeling of donor hematopoietic cells after transplantation in Fanconi Anemia.

Donor-derived hematopoietic cells after HCT in Fanconi anemia retain a dysfunctional metabolic and redox phenotype, with impaired mitochondrial oxidative phosphorylation and persistent lipid/protein oxidation.

• Why it matters: HCT restores donor haematopoiesis in Fanconi anemia but leaves the recipient microenvironment genetically uncorrected, leaving unclear how persistent FA stromal signals shape donor-cell biology.
• What they did: Peripheral blood and available bone marrow samples from FA patients before and after HCT, plus SAA transplant controls, were profiled for mitochondrial function, energy status, oxidative damage, cytokines, DNA methylation, and ex vivo persistence after 96 h.
• The result: A pro-inflammatory, pro-oxidative recipient environment after HCT was linked to donor-cell mitochondrial/energy dysfunction and an intermediate FA-associated DNA methylation episignature; conditioned media from FANCA-deficient stromal cells reproduced these abnormalities, and targeting inflammatory pathways or mitochondrial oxidative stress improved energy homeostasis and reduced oxidative damage.