title: Spectral karyotyping in patients with acute myeloid leukemia and a complex karyotype shows hidden aberrations, including recurrent overrepresentation of 21q, 11q, and 22q.
abstract: We used spectral karyotyping (SKY) to study 29 adults with acute myeloid leukemia and a complex karyotype containing one to nine abnormalities that were not fully identifiable by G-banding. SKY showed the origin of rings and unidentified material in unbalanced translocations in all cases and the origin of markers in most, allowing reinterpretation of 136 aberrations and discovery of three aberrations hidden in normal chromosomes. SKY confirmed 10 and refined the interpretation of three balanced aberrations recognized by G-banding and identified another nine balanced aberrations, including a novel translocation involving the RUNX1 gene. Eleven of 32 deletions found by G-banding were shown to be cryptic translocations or insertions, including three of four chromosome 3 deletions, two of three del(7q), and two of 12 del(5q). Of the 92 chromosomes deemed lost entirely by G-banding, 63 (68%) were shown to be involved in structural aberrations. This was especially true for -21 (eight of eight patients), -5 (five of six patients), -20 (seven of nine patients), and -18 (six of 12 patients). Unexpectedly, SKY uncovered a hidden overrepresentation of segments from at least one chromosome in 21 patients. The most frequently overrepresented was 21q, found in eight patients, including four with high-level 21q amplification. Fluorescence in situ hybridization showed that the RUNX1 gene was not the target of amplification in seven of these patients. Also frequently gained were 11q (in seven patients, including three with high-level MLL gene amplification) and 22q (in seven patients). We conclude that SKY considerably enhances the accuracy of karyotype interpretation, and that amplification of chromosomal material may play a greater role in leukemogenesis than has been recognized.
authors.affiliation: Division of Hematology and Oncology and the Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210-1228, USA. Mrozek-1@medctr.osu.edu
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Kristiina
authors.initials: K
authors.lastname: Heinonen
authors.forename: Karl S
authors.initials: KS
authors.lastname: Theil
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance / Q000235:genetics; D002869:Chromosome Aberrations; D002871:Chromosome Banding / Q000379:methods; D020223:Chromosome Painting / Q000379:methods; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007621:Karyotyping / Q000379:methods; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged