title: Do somatic mutations in de novo MDS predict for response to treatment?
abstract: A 68-year-old male with history of hypertension and arthritis presented with bruising and increasing fatigue over several months. He was found to be thrombocytopenic (platelets 30), WCB 2.0 K/mm(3), Hg 11.6 g/dL, ANC 870, and 1% circulating blasts. Bone marrow biopsy revealed 40%-50% cellular with multilineage dysplasia and 10% blasts. Cytogenetic genetic studies showed trisomy 2, and translocation (3;21). FISH studies for 5q, 7p, 8, 17p, and 20q abnormalities were negative. Molecular diagnostics were sent to a commercial laboratory to aid in prognostication. These studies showed mutations in TET2 (exons 1- 9 tested) and PHF6 (exons 1-9 tested). No abnormalities in other epigenetic regulators (DNMT3A, ASXL1), RNA splicing (SF3B1, SRSF2, URAF1, ZRSR2), transcription factors (RUNX1 or ETV6), or signaling (CBL, NRAS, KIT, JAK2, MPL) were detected. He was referred for consultation regarding initial treatment. In this elderly patient with preserved organ function and good performance status who is being considered for reduced intensity conditioned allogeneic hematopoietic cell transplant, what should the initial treatment be and can we use the molecular diagnostic results to guide therapy?
authors.affiliation: Washington University Medical School, St Louis, MO; and.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schroeder
authors.affiliation: The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Amy E
authors.initials: AE
authors.lastname: DeZern
mesh_terms: D000368:Aged; D044127:Epigenesis, Genetic; D005091:Exons; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000628:therapy*; D011379:Prognosis; D012326:RNA Splicing; D015398:Signal Transduction; D014184:Transplantation, Homologous; D016896:Treatment Outcome