The impact of clonal diversity and mosaicism on haematopoietic function in Fanconi anaemia

Recent advances have facilitated studies of the clonal architecture of the aging haematopoietic system, and provided clues to the mechanisms underlying the origins of hematopoietic malignancy. Much less is known about the clonal composition of haematopoiesis and its impact in bone marrow failure (BMF) disorders, including Fanconi anaemia (FA). Understanding clonality in FA is likely to inform both the marked predisposition to cancer and the rapid erosion of regenerative reserve seen with this disease. This may also hold broader lessons for haematopoietic stem cell biology in other diseases with a clonal restriction. In this review, we focus on the conceptual basis and available tools to study clonality, and highlight insights in somatic mosaicism and malignant evolution in FA in the context of haematopoietic failure and gene therapy.

Automated summary

Recent advances have led to a better understanding of the clonal architecture of the aging hematopoietic system and its impact on bone marrow failure disorders, including Fanconi anemia (FA). Studying clonality in FA may provide insights into the predisposition to cancer and rapid decline in regenerative reserve. These findings could also have broader implications for hematopoietic stem cell biology in other diseases with clonal restrictions.