Inherited bone marrow failure syndromes in 2012.

Inherited bone marrow failure syndromes (CBMFS) are a heterogeneous group of genetic disorders characterized by bone marrow failure, congenital anomalies, and an increased risk of malignant disease. The representative diseases with trilineage involvement are Fanconi anemia and dyskeratosis congenita, while the disease with the single lineage cytopenia is Diamond-Blackfan anemia. Recent advances in our understanding of these diseases have come from the identification of genetic lesions responsible for the disease and their pathways. Although recent studies have identified many causative genes, mutations of these genes have only been found in less than half of the patients. Next-generation sequencing technologies may reveal new causative genes in these patients. Also, induced pluripotent stem cells derived from patients with CBMFS will be useful to study the pathophysiology of the diseases. The only long-term curative treatment for bone marrow failure in patients with inherited bone marrow failure syndromes is allogeneic hematopoietic stem cell transplantation, although this procedure has a risk of severe adverse effects. Multicenter prospective studies are warranted to establish appropriate conditioning regimens aimed at reducing transplant-related mortality.