1. Natural gene therapy by reverse mosaicism leads to improved hematology in <scp>Fanconi</scp> anemia patients
- Author
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Cristina Beléndez, Jonathan D. Schwartz, Monica Lopez, Estela Carrasco, Gayatri R Rao, Jordi Minguillón, Judith Balmaña, Roser Pujol, Eileen Nicoletti, José A. Casado, María José Ramírez, Massimo Bogliolo, Jordi Surrallés, Albert Català, Julián Sevilla, Cristina Díaz de Heredia, Susana Navarro, Juan A. Bueren, Paula Río, Bienvenida Argilés, Juan Pablo Trujillo-Quintero, and Isabel Badell
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Adolescent ,SOMATIC MOSAICISM ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Fanconi anemia ,Internal medicine ,medicine ,Humans ,Progenitor cell ,Child ,Hematology ,Mosaicism ,business.industry ,Bone marrow failure ,Hematopoietic stem cell ,Genetic Therapy ,medicine.disease ,Leukemia ,Fanconi Anemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,CELLS ,Cohort ,Bone marrow ,business ,030215 immunology - Abstract
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 to evaluate the clinical course of a cohort of FA mosaic patients followed at referral centers in Spain over a 30-year period. This cohort includes patients with a majority of T cells without chromosomal aberrations in the DEB-chromosomal breakage test. Relative to non-mosaic FA patients, we observed a higher proportion of adult patients in the cohort of mosaics, with a later age of hematologic onset and a milder evolution of (BMF). Consequently, the requirement for hematopoietic stem cell transplant (HSCT) was also lower. Additional studies allowed us to identify a sub-cohort of mosaic FA patients in whom the reversion was present in bone marrow (BM) progenitor cells leading to multilineage mosaicism. These multilineage mosaic patients are older, have a lower percentage of aberrant cells, have more stable hematology and none of them developed leukemia or myelodysplastic syndrome when compared to non-mosaics. In conclusion, our data indicate that reverse mosaicism is a good prognostic factor in FA and is associated with more favorable long-term clinical outcomes.
- Published
- 2021