Progression of myelodysplastic syndrome: allelic loss on chromosomal arm 1p.
Myelodysplastic syndrome (MDS) is a common neoplasm of haematopoietic pluripotent stem cells. Although one third of MDS patients evolve to acute myeloid leukaemia (AML), little is understood about the mechanisms responsible for this progression. We have previously detected the frequent loss of heterozygosity (LOH) on the short arm of chromosome 1 in blast crisis of chronic myelocytic leukaemia. In this study, we examined the chromosomal arm 1p for allelic loss in the progression of MDS to AML, using 17 microsatellite markers spanning chromosome 1 in 20 patients who progressed from MDS to AML. DNA was extracted from slides of bone marrow smears. In each patient, DNA from MDS was analysed alongside DNA from AML. Allelic loss on 1p was observed in six of the 20 individuals (30%). Serial cytogenetic information was available in five of the six patients with LOH on 1p; no deletions in this region were detected. Three samples showed LOH at all informative loci on 1p. The other three samples showed LOH on at least one but not all loci on 1p with consensus regions of LOH located distal to D1S253 (1p36.3) and probably proximal to D1S496 (1p32-). Our results suggest that tumour suppressor genes that play an important role in the progression of MDS to AML may reside in at least two different regions on 1p.
Mori
Naoki
N
Department of Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA.
Morosetti
Roberta
R
Mizoguchi
Hideaki
H
Koeffler
H Phillip
HP
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D002878:Chromosomes, Human, Pair 1; D020732:Cytogenetic Analysis; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*