Overview of inherited bone marrow failure syndrome

Abstract

The 2016 revision of the WHO classification of tumors of hematopoietic and lymphoid tissues proposed a section on myeloid tumors with a germline predisposition. In inherited bone marrow failure syndrome, the differentiation and proliferation of hematopoietic cells are impaired by a genetic predisposition, resulting in single-line cytopenia and pancytopenia. Its clinical diagnosis has been made on the basis of the characteristic physical findings. Prototype diseases include the following. Fanconi anemia is a disorder of genomic instability in DNA cross-linking. Dyskeratosis congenita is a disorder of poor telomere maintenance. Diamond-Blackfan anemia and Shwachman-Diamond syndrome are disorders of ribosome dysfunction. In recent years, owing to advances in genetic analysis, novel inherited bone marrow failure syndromes have been established, whose causative genes are SAMD9, SAMD9L, MECOM, and ERCC6L2. Biallelic mutation in ADH5 combined with polymorphism in ALDH2 has also been identified. Environmental factors in the presence of genetic predisposition modify disease courses, and DNA damage causes additional abnormalities in hematopoietic stem cells, resulting in oncogenesis. On the other hand, reversion mutation is occasionally acquired and the condition is improved in such cases. Hematopoietic cell transplantation is an important treatment for the cure of inherited bone marrow failure syndrome; however, there remain many issues such as its indication and timing, selection of donors, preconditioning, post-transplant complications, and secondary cancer. Appropriate medical care should be provided on the basis of the characteristics of each type of inherited bone marrow failure syndrome.