Clonal Chromosomal Aberrations in Bone Marrow Cells of Fanconi Anemia Patients: Results and Implications

Fanconi anemia patients have a high risk for bone marrow failure, aplastic anemia, myelodysplastic syndrome, and acute myeloid leukemia. Many FA patients acquire chromosomal aberrations in their bone marrow (BM) cells. The significance and predictive value of these somatic aberrations for hematopoietic function and malignant progress are not fully understood. Therefore, we initiated in cooperation with the ‘Deutsche Fanconi-Anamie-Hilfe e.V.’ a prospective cytogenetic follow-up in BM cells of FA patients utilizing systematically molecular cytogenetic techniques. The most frequent clonal aberrations are gains of material of the long arm of chromosome 3, loss of most of the long arm of chromosome 7 or loss of one entire copy of chromosome 7, and gains of the long arm of chromosome 1. The available data suggest that these clonal chromosome aberrations in bone marrow cells of FA patients represent an important step in the initiation of MDS and AML. Our data of patients with 3q aberrations revealed that gains of 3q are an adverse risk factor. The overall survival in the 3q group was extremely poor compared to FA patients without such aberrations. None of the FA patients with 3q gains survived without undergoing HSCT. Because of the high MDS/AML risk and the significantly higher mortality in the group of FA patients with 3q aberrations, we recommend a systematic evaluation of all FA patients by molecular cytogenetics in order to detect aberrations, including subtle aberrations, as early as possible. Such clonal aberrations are a very strong clinical warning sign. All available evidence suggests that the finding of any chromosomal abnormality in bone marrow cells, especially abnormalities involving chromosomes 3 and 7, warrant very close clinical follow-up, as they may signal the development of MDS or AML.