title: Non-dysplastic myelodysplasia?
abstract: Patients successfully treated for a malignancy with cytotoxic therapy have an increased risk of developing secondary myelodysplasia (MDS) and acute myeloid leukemia (AML). We report a patient in remission from Hodgkin's disease (HD) who remains hematologically normal 4 years after combination chemotherapy, but who has biological and genetic abnormalities characteristic of myelodysplasia. X-inactivation analysis using a 5' phosphoglycerate kinase (PGK) probe demonstrates polyclonal hematopoiesis, but cytogenetic analysis reveals a clonal population with a minority of metaphases having a 7q-deletion. NRAS mutations are not detectable 1 year after treatment, but are present in two separate clones (at codons 12 and 15) analyzed by single-stranded conformational polymorphism (SSCP), followed by cloning and sequencing 4 years after treatment. The presence of an activated NRAS with the same codon 12 mutation was independently confirmed by the nude mouse tumorigenicity assay. In vitro peripheral blood granulocyte-macrophage colony-forming units (CFU-GM) have changed from normal to undetectable levels while erythroid burst forming units (BFU-E) were significantly reduced on two occasions during the period of observation. These abnormalities are characteristic of MDS. Continued clinical follow-up will determine whether these evolving genetic and biological abnormalities pre-date the onset of clinical and morphological features of MDS.
authors.affiliation: Leukemia Research Fund Preleukemia Unit, Hematology Department, University of Wales College of Medicine, Cardiff, UK.
authors.forename: P G
authors.initials: PG
authors.lastname: Cachia
authors.forename: C
authors.initials: C
authors.lastname: Taylor
authors.forename: P W
authors.initials: PW
authors.lastname: Thompson
authors.forename: G B
authors.initials: GB
authors.lastname: Tennant
authors.forename: G
authors.initials: G
authors.lastname: Masters
authors.forename: T
authors.initials: T
authors.lastname: Pettersson
authors.forename: J A
authors.initials: JA
authors.lastname: Whittaker
authors.forename: A K
authors.initials: AK
authors.lastname: Burnett
authors.forename: A
authors.initials: A
authors.lastname: Jacobs
authors.forename: R A
authors.initials: RA
authors.lastname: Padua
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D003131:Combined Modality Therapy; D004303:Dosage Compensation, Genetic; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006689:Hodgkin Disease / Q000628:therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000235:genetics; D017354:Point Mutation