Non-dysplastic myelodysplasia?
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.
Cachia
P G
PG
Leukemia Research Fund Preleukemia Unit, Hematology Department, University of Wales College of Medicine, Cardiff, UK.
Taylor
C
C
Thompson
P W
PW
Tennant
G B
GB
Masters
G
G
Pettersson
T
T
Whittaker
J A
JA
Burnett
A K
AK
Jacobs
A
A
Padua
R A
RA
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