Towards Improved Decision-Making Based on Genomics in Bone Marrow Failure

Inherited and acquired bone marrow failure syndromes (BMF) may be difficult to distinguish due to heterogeneity and overlap of clinical phenotypes. Genomic screening has been increasingly used to identify mutations in BMF-related genes that are known to be etiologic in inherited BMF. However, genomic testing is expensive, results may not return for several seeks, and findings can be difficult to interpret as some reported variants are of unclear clinical significance. To guide the decision-making for genetic testing and results interpretation, we aimed to identify clinical and molecular parameters associated with a higher probability of patients having an inherited disease. We screened 323 BMF patients from two independent cohorts for germline mutations in BMF-related genes using a targeted next-generation sequencing (NGS) assay, and correlated the results with patients' prior diagnosis, family history, telomere length (TL), karyotype, and the presence of a paroxysmal nocturnal hemoglobinuria (PNH) clones.Patients were followed at the Hematology Branch of NHLBI (NHLBI, n=179) and the Ribeirão Preto Medical School, University of São Paulo (USP, n=144). Diagnoses included were severe (SAA) and moderate aplastic anemia (MAA), isolated cytopenias, myelodysplastic syndrome (MDS), hypocellular MDS (HypoMDS), dyskeratosis congenita (DC), and Diamond-Blackfan anemia (DBA). Patients were classified as suspected to have inherited BMF (phenotype suggestive for constitution...
Source: Blood - Category: Hematology Authors: Tags: 508. Bone Marrow Failure: Poster II Source Type: research