Acute lymphoblastic leukemias with normal karyotypes are not without genomic aberrations.

Current cytogenetic techniques have enabled more accurate definition of genetic aberrations in the lymphoblasts of patients with acute lymphoblastic leukemia (ALL), at least in most cases. Detecting the cryptic aberrations undetected by conventional cytogenetic methods is important for disease classification, evaluation of prognosis, and minimal residual disease follow-up. We have studied DNA copy number alterations of 27 adolescent ALL patients with normal (n=26) or failed (n=1) karyotype at diagnosis using microarray comparative genomic hybridization (CGH). Aberrations were detected in 85% of cases, deletions being more frequent (39 in 19 patients) than gains (14 in 10 patients). Deletions of 9p21.3 were the most common aberration, and 41% of deletions were cryptic and <5 Mb in size. We conclude that ALL without any form of genetic alteration probably does not exist. Microarray CGH is a powerful tool to reveal otherwise cryptic aberrations in adolescent ALL.