Recurrent Chromosome Abnormalities Define Nonoverlapping Unique Subgroups of Tumors in Patients With Chronic Lymphocytic Leukemia and Known Karyotypic Abnormalities

BackgroundA major conclusion drawn from the accumulated cytogenetic data on solid tumors and some hematologic malignancies is that tumors progress by the acquisition of chromosomal changes, as reflected by more aggressive tumors containing a larger number of chromosomal abnormalities. An additional observation is that some chromosomal changes appear early in the disease progression, and some others appear late.Material and MethodsOn the basis of this information, a model for karyotypic evolution in chronic lymphocytic leukemia (CLL) is presented. The Mitelman Database of Chromosomes in Cancer was searched, and 1749 abnormal karyotypes were assessed. The main clones were analyzed, and chromosomal gains and losses were used to design a model of genetic acquisition based on the calculation of a variable called time to occurrence (TO).ResultsOur comprehensive study of genetic abnormalities in a large number of CLL karyotypes revealed that most CLL has 2 chromosomal aberrations at diagnosis. Moreover, the temporal analysis suggests that trisomy 12 is an early event in the biological evolution of CLL.ConclusionThese results highlight the possibility of targeted therapies affecting the genes located on this chromosome (cyclin D, cyclin D2, cyclin-dependent kinase 2, and cyclin-dependent kinase 4).