Trisomy 21 is a recurrent secondary aberration in childhood acute lymphoblastic leukemia with TEL/AMLI gene fusion

TEL/AML1 gene fusion is the most frequent genetic lesion in pediatric acute lymphoblastic leukemia (ALL). It occurs as a consequence of the cryptic ch romosomal translocation t(12;21)(p13;q22). In a cohort of 50 RT-PCR-positiv e TEL/AML1 patients, karyotype examination by GTG banding and fluorescence in situ hybridization (FISH) allowed us to identify chromosome anomalies in addition to the already existing t( 12;21). Secondary aberrations were fou nd in 29 out of 41 patients (71%) at initial diagnosis and in all 9 patient s with relapse. Structural rearrangements affected chromosome arms 2p, 2q, 5q, 9p, 12p (n = 2), 6q, 11p (n = 3), and 21q (n = 4). An extra chromosome 21 was found to be the most frequent anomaly. It was detected in 6 out of 4 1 patients at initial diagnosis (15%) and in 7 out of the 9 patients at rel apse. No karyotype with trisomy 21 exceeded 47 chromosomes. Gain of chromos ome 21 was the sole anomaly in GTG-banding analysis in 2/41 patients at ini tial diagnosis and in 4/9 at relapse. Notably, chromosome painting analysis performed in 11 out of the 13 patients with an extra chromosome 21 reveale d duplication of the normal chromosome 21 in 8, and duplication of der(21)t (12;21) in 3 patients. Furthermore, gain of der(21)t(12;21) chromosome was confined exclusively to the relapse patients. Genes Chromosomes Cancer 24:2 72-277 1999. (C) 1999 Wiley-Liss, Inc.