The application of comparative genomic hybridization as an additional toolin the chromosome analysis of acute myeloid leukemia and myelodysplastic syndromes

In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) there a re frequently complex karyotypes with multiple structurally altered chromos omes, many of which are marker chromosomes of unknown origin. The aim of th is study was to apply comparative genomic hybridization (CGH) to cases of A ML or MDS in transformation submitted for routine cytogenetic analysis to i nvestigate whether this approach would yield any further information and. i f possible, to predict which cases would benefit from CGH analysis. Ninetee n casts with AML or MDS in transformation were analyzed. CGH revealed nine cases with gains or losses of chromosomal material. In six of these cases t he chrornosomal location of this material was not apparent from cytogenetic analysis especially when multiple markers were present. By using fluoresce nce in situ hybridization (FISH) with specific Libraries for the chromosome regions that showed discordance between CGH and conventional cytogenetics, we were able to identify the chromosome location of material within the ka ryotype. In this group of six patients, four cases of an unbalanced translo cation involving regions of chromosomes 5 and 17 were characterized. Three of these cases had additional abnormalities, including two cases with regio ns of amplification in which oncogenes are located (MYC, MLL) and one case with a dic(7;21)(p10:p10). In all six cases it was possible to characterize complex chromosomal aberrations such as derivative chromosomes, marker chr omosomes, and ring chromosomes. This study demonstrates that CGH can detect true gain and loss of critical chromosome regions more accurately than con ventional karyotyping in cases with very complex karyotypes, and can thus p rove useful in predicting prognosis and pinpointing areas of the genome tha t require further study. Also, CGH can be a useful technique to identify th e origin of marker chromosomes, and it can assist in choice of probes for c onfirmatory FISH, when there is no clue provided from the analysis of G-ban ded chromosomes. (C) 2001 Elsevier Science Inc. All rights reserved.