Gene amplification in myeloid leukemias elucidated by fluorescence in situ hybridization

Gene amplification in hematologic malignancies is uncommon. When karyotyping leukemia cells, gene amplification is generally seen as double-minute (dmin) chromosomes and homogeneously staining regions (hsr). One of the more commonly amplified regions is MYC at 8q24.21, but amplification of MLL at 11q23 and regions on 9p, 19q, and elsewhere on 11q have been reported. Increased copy number of these genes has been associated with poor prognosis. Over an 11-year period, we identified 31 cases of possible gene amplification, 27 of which had enough sample material for further investigations. A total of 17 cases had dmin only, 13 cases had hsr only, and 1 case had both dmin and hsr in the karyotype. Fluorescence in situ hybridization (FISH) analysis identified amplification of MYC in 12 cases, all on dmin, and amplification of MLL in eight cases, all on hsr. Regions other than MYC and MLL were amplified in eight cases and, using multicolor FISH and multicolor banding, we identified a number of novel regions of amplification: 13q11 approximately q12.1, 15q26.1 approximately q26.3, and 17q12. We also identified one case where two different chromosomal regions were simultaneously amplified in the same cell line.