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

IF 2 4区 医学 Q3 ONCOLOGY
Alberto Fresa, Simona Sica
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引用次数: 0

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.

bcra1 /2突变健康携带者是否可以作为造血干细胞捐献的有效候选者?
brca突变的健康造血干细胞(hsc)供体的突变状态是否会对移植产生影响尚不清楚。比较现有的文献研究,我们关注BRCA突变与血液恶性肿瘤和范可尼贫血(FA)发展之间的相关性;然后,我们探讨了BRCA突变存在下造血干细胞的类型、频率和功能,以及化疗和放疗后造血功能的重建。BRCA突变在FA中的作用表明可能参与了该疾病的发病;突变携带者确实没有表现出FA的任何典型表型。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,即使小鼠模型试图显示完全突变、单倍不足和正常造血干细胞之间的可能差异,我们也不知道BRCA突变的造血干细胞是否可以补偿一种调节方案。因此,考虑到突变对造血功能的下调作用,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突变供体的造血干细胞可能是有问题的。
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来源期刊
CiteScore
3.10
自引率
5.90%
发文量
38
审稿时长
>12 weeks
期刊介绍: Hereditary Cancer in Clinical Practice is an open access journal that publishes articles of interest for the cancer genetics community and serves as a discussion forum for the development appropriate healthcare strategies. Cancer genetics encompasses a wide variety of disciplines and knowledge in the field is rapidly growing, especially as the amount of information linking genetic differences to inherited cancer predispositions continues expanding. With the increased knowledge of genetic variability and how this relates to cancer risk there is a growing demand not only to disseminate this information into clinical practice but also to enable competent debate concerning how such information is managed and what it implies for patient care. Topics covered by the journal include but are not limited to: Original research articles on any aspect of inherited predispositions to cancer. Reviews of inherited cancer predispositions. Application of molecular and cytogenetic analysis to clinical decision making. Clinical aspects of the management of hereditary cancers. Genetic counselling issues associated with cancer genetics. The role of registries in improving health care of patients with an inherited predisposition to cancer.
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