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.

中文翻译：

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BCRA1 / 2突变健康携带者是否应该成为造血干细胞捐赠的有效候选人？

尚不清楚BRCA突变的健康造血干细胞（HSCs）供体的突变状态是否会影响植入。比较文献中的研究，我们关注BRCA突变与血液系统恶性肿瘤和Fanconi贫血（FA）的发展之间的相关性。然后，我们探讨了在存在BRCA突变的情况下HSC的类型，频率和功能，以及化疗和放射治疗后造血功能的重建。BRCA突变在FA中的作用表明可能与疾病的发作有关。实际上，突变携带者没有显示出FA的典型表型的任何迹象。BRCA突变状态可被认为是血液系统恶性肿瘤的危险因素，但仅适用于继发性恶性肿瘤和/或存在骨髓应激因素的情况。目前，即使鼠模型试图显示完全突变的，单倍剂量不足的和正常的HSC之间可能存在的差异，我们也不知道是否可以通过BRCA突变的HSC来补偿条件疗法。因此，考虑到突变对造血作用的下调作用，在另一个具有相同相容性的可用供体存在的情况下，使用BRCA突变的供体的HSC可能会产生问题。