The deficiencies cause increased risk of hemorrhage and recurrent infections, respectively.As FA is now known to affect DNA repair, specifically homologous recombination, and given the current knowledge about dynamic cell division in the bone marrow, patients are consequently more likely to develop bone marrow failure, myelodysplastic syndromes, and acute myeloid leukemia (AML). Myelodysplastic syndromes
MDSs, formerly known as preleukemia, are a group of bone marrow neoplastic diseases that share many of the morphologic features of AML, with some important differences. First, the percentage of undifferentiated progenitor cells, blast cells, is always less than 20%, with considerably more dysplasia, defined as cytoplasmic and nuclear morphologic changes in erythroid, granulocytic, and megakaryocytic precursors, than what is usually seen in cases of AML. These changes reflect delayed apoptosis or a failure of programmed cell death. When left untreated, MDS can lead to AML in about 30% of cases. Due to the nature of the FA pathology, MDS diagnosis cannot be made solely through cytogenetic analysis of the marrow. Indeed, it is only when morphologic analysis of marrow cells is performed, that a diagnosis of MDS can be ascertained. Upon examination, MDS-affected FA patients will show many clonal variations, appearing either prior or subsequent to the MDS. Furthermore, cells will show chromosomal aberrations, the most frequent being monosomy 7 and partial trisomies of chromosome 3q 15.
Clinical trial number NCT03070392 for "Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma" at ClinicalTrials.gov