Late appearance of the 11q22.3-23.1 deletion involving the ATM locus in B-cell chronic lymphocytic leukemia and related disorders. Clinico-biological significance

Background and Objectives. Chromosome 11q22.3-23.1 deletions involving the ataxia-teleangiectasia mutated (ATM) locus (11q-/ATM+/-) are detected at diagnosis in 10-20% of cases of B-cell chronic lymphocytic leukemia (CLL) and are associated with a relatively aggressive disease. The aim of this study was to ascertain whether 11q-/ATM+/- may appear late during the course of the disease and to analyze its possible correlation with disease evolution. Design and Methods. Eighty-two patients with CLL and related disorders, i.e. CLL/PL and prolymphocytic leukemia (PLL), without 11q- at diagnosis were sequentially ascertained at 1-2 year intervals by conventional cytogenetic analysis (CCA) and fluorescence in situ hybridization (FISH), using an ATM-specific probe. Results. Eight patients acquired a submicroscopic 11q deletion 13-43 months after diagnosis: the diagnosis at presentation was CLL in 3 cases, CLL/PL in 3 cases and PLL in 2 cases. A 13q14 deletion preceded the development of 11q- in four patients; additional aberrations included +12 (three cases), 17p13 deletion and 6q21 deletion (one case each). The acquisition of the 11q deletion was more frequently found in those patients presenting with CLL/PL and PLL than typical CLL (p=0.0016) and with splenomegaly (p=0.003). Follow-up data showed that karyotype evolution (p=0.009) and cytological transformation (p