Twenty-four-color spectral karyotyping reveals chromosome aberrations in cytogenetically normal acute myeloid leukemia

Multicolor spectral karyotyping allows simultaneous visualization of all hu man chromosomes and screening for chromosomal rearrangements without a prio ri knowledge of any abnormalities involved. Based on this potentially incre ased sensitivity, we investigated, in a preliminary manner, whether spectra l karyotyping could detect cytogenetic aberrations in karyotypically normal leukemia. The test population was comprised of 28 cryopreserved, cytogenet ically normal acute myeloid leukemia (AML) samples from patients registered to a randomized trial for previously untreated AML (SWOC 9031). Two normal and 12 samples with known cytogenetic aberrations were used to validate an d establish the diagnostic accuracy of the spectral karyotyping assay and i nstrumentation in a clinical setting. Enumeration and region-specific DNA f luorescence in situ hybridization (FISH) probes verified discrepant results . In the validation data set, spectral karyotyping refined complex karyotyp ic rearrangements in six cases and defined the chromosomal origin of a "jum ping" homogeneously staining region; however, the technology was less sensi tive in the detection of subtelomeric rearrangements and double minute chro mosomes. In the test population, spectral karyotyping identified previously undetected cytogenetic aberrations In two cases (7%) of karyotypically nor mal AML: a cryptic 11q23 translocation in 20/20 cells and a minor monosomy 7 clone in 3/21 cells (FISH, 10.5%). Both of these abnormalities are consid ered to confer a poor prognosis when based on classical cytogenetic prognos tic criteria. As an adjunct to classical cytogenetics and standard FISH ana lyses, the additive resolution of spectral karyotyping, in particular, with chromosome paints spiked with subtelomeric and/or locus-specific probes, m ay allow significant gains to be made in diagnostic accuracy and recognitio n of genotype/phenotype prognostic relationships, and in defining underlyin g biologic mechanisms in cancer. (C) 2000 Wiley-Liss, Inc.