Natural gene therapy by reverse mosaicism leads to improved hematology in <scp>Fanconi</scp> anemia patients

Fanconi anemia (FA) is characterized by chromosome fragility, bone marrow failure (BMF) and predisposition to cancer. As reverse genetic mosaicism has been described as “natural gene therapy” in patients with FA, we sought evaluate the clinical course of a cohort FA mosaic followed at referral centers Spain over 30-year period. This includes majority T cells without chromosomal aberrations DEB-chromosomal breakage test. Relative non-mosaic patients, observed higher proportion adult mosaics, later age hematologic onset milder evolution (BMF). Consequently, requirement for hematopoietic stem cell transplant (HSCT) was also lower. Additional studies allowed us identify sub-cohort whom reversion present (BM) progenitor leading multilineage mosaicism. These are older, have lower percentage aberrant cells, more stable hematology none them developed leukemia or myelodysplastic syndrome when compared non-mosaics. In conclusion, our data indicate that good prognostic factor associated favorable long-term outcomes.