Genomic profiling in high hyperdiploid acute myeloid leukemia: a retrospective study of 19 cases

Among patients with acute myeloid leukemia (AML), the rare group of complex aberrant karyotypes characterized by high hyperdiploidy (HH) is a subset with poor prognosis. Because of their rarity, few conventional cytogenetic studies have specifically addressed these patients. To identify DNA copy number aberrations at the submicroscopic level, we applied array-based comparative genomic hybridization (aCGH) to samples from 19 AML patients with complex karyotypes characterized by HH (≥49 chromosomes). We found a total of 155 imbalances (average: 8.2 per patient), and a high proportion of these imbalances involved whole chromosomes (n = 75). The chromosomes most commonly gained were chromosomes 8 (58%), 21 (42%), and 19 (32%). We identified 80 segmental genomic aberrations, and losses (n = 47) were more frequent than gains (n = 33). We identified common deleted regions at 5q, 15q, 18p, and 19p. The tumor suppressor gene L3MBTL4 and zinc finger proteins reside within 18p and 19p, respectively. The aCGH analysis added new information to the karyotypic interpretations in 16 of the 19 HH AML cases (84%), leading to a significantly higher detection rate of abnormalities.