Should the BCRA1/2-mutations healthy carriers be valid candidates for hematopoietic stem cell donation?

Abstract

It's still not clear whether the mutational status of BRCA-mutated healthy hematopoietic stem cells (HSCs) donors could have an impact on the engraftment. Comparing the studies present in literature, we focused on the correlation between BRCA mutations and the development of hematological malignancies and Fanconi anemia (FA); then, we explored HSCs types, frequencies, and functions in the presence of BRCA mutations, as well as the reconstitution of hematopoiesis after chemotherapy and radiation treatments. The role of BRCA mutations in the FA showed a possible involvement in the onset of the disease; the mutation carriers, indeed, did not show any sign of the typical phenotype of the FA. BRCA mutational status can be considered as a risk factor for hematological malignancies, but only for secondary malignancies and/or in the presence of bone marrow stress factors. Currently we don't know if a conditioning regimen could be compensated by BRCA mutated HSCs, even if murine models tried to show the possible differences between fully mutated, haploinsufficient and normal HSCs. Thus, given the downregulating effect of the mutations on hematopoiesis, it could be questionable to use the HSCs of a BRCA-mutated donor in the presence of another available donor with the same compatibility.