Cytogenetic and FISH studies of a single center consecutive series of 152 childhood acute lymphoblastic leukemias

Between 1977 and 1996, cytogenetic investigations were performed on 182 chi ldhood (less than or equal to 16 yr) acute lymphoblastic leukemias (ALL), c onstituting 94% (182 of 194) of all ALL patients diagnosed and treated at t he Departments of Pediatrics, Lund and Malmo University Hospitals, Sweden, during these two decades. The cytogenetic analyses were successful in 152 c ases (84%). The failure rate was higher for the ALL investigated before 198 7 (30% vs. 4%, p<0.0001), and also the incidence of cytogenetically normal cases was higher during 1977-86 (43% vs. 25%, p<0.05). Clonal chromosomal a bnormalities were found in 103 (68%) ALL. Structural rearrangements were de tected, by chromosome banding alone, in 76 cases (50%). Fluorescence in sit u hybridization (FISH) was used to identify cases with t(12;21), 11q23 rear rangements, and 9p deletions, using probes for ETV6/CBFA2, MLL, and CDKN2A/ B, in 72 cases from which cells in fixative and/or unstained metaphase prep arations were available. In total, the most common structural rearrangement s were del(9p) (17%), t(12;21) (15%), del(6q) (8%), and MLL rearrangements (4%). Six (32%) of nineteen cytogenetically normal ALL analyzed by FISH har bored cryptic abnormalities; three displayed t(12;21) and four had del(9p), one of which also carried a t(12;21). Five (45%) of the t(12;21)-positive ALL showed + der(21)t(12;21) or ider(21)(q10)t(12;21), resulting in the for mation of double fusion genes. Among the more rare aberrations, eight struc tural rearrangements were identified as novel recurrent ALL-associated abno rmalities, and nine cases harbored rearrangements previously not reported. Sixteen cases displayed karyotypically unrelated clones at different invest igations. Seven ALL (5%) showed simple chromosomal changes, unrelated to th e aberrations detected at diagnosis, during morphologic and clinical remiss ion, and in all but one instance the patients remained in remission, with t he abnormal clone disappearing in subsequent investigations. This indicates that the emergence of novel clonal chromosomal aberrations during remissio n in childhood ALL is rather common and does not by necessity predict a for thcoming relapse.