title: Myeloid lineage-selective growth of revertant cells in Fanconi anaemia.
abstract: Fanconi anaemia (FA) is a genetically heterogeneous chromosome instability syndrome characterised by bone marrow failure and congenital anomalies. Although an increasing number of reports suggest that reversion mosaicism noted in peripheral blood lymphocytes (PBLs) is associated with mild haematopoietic failure in FA, myeloid cells are rarely directly examined. We here report a patient with prolonged mild pancytopenia in whom proliferation of revertant cells was detected in mature myeloid cells but not in PBLs. While this patient had inherited heterozygous mutations, 2546delC and 3720-3724del, in the major FA gene FANCA, Epstein-Barr virus-immortalised lymphoblastoid cells from the patient had 2546C > T instead of 2546delC, resulting in expression of a functional missense protein. As the identical reversion was detected in polymorphonuclear granulocytes and mononuclear phagocytes, sustained haematopoiesis in the patient can be attributed to a selective growth advantage of revertant myeloid cells. It is noteworthy that such a myeloid lineage-selective mosaicism is overlooked in routine examination of PBLs. Recognition of this status will expand the role of reversion mosaicism in the pathophysiology of FA.
authors.affiliation: Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hamanoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagasaki
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Tsuruta
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Oda
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yabe
authors.forename: Miharu
authors.initials: M
authors.lastname: Yabe
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000473:pathology*; D049109:Cell Proliferation; D005199:Fanconi Anemia / Q000473:pathology*; D005260:Female; D006579:Heterozygote; D006801:Humans; D020125:Mutation, Missense; D022423:Myeloid Cells / Q000473:pathology; D010198:Pancytopenia / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology