Characterization of additional genetic events in childhood acute lymphoblastic leukemia with TEL/AML1 gene fusion: a molecular cytogenetics study

TEL/AML1 gene fusion that results from a cryptic t(12;21) is the most commo n genetic aberration in childhood B-lineage acute lymphoblastic leukemia (A LL). While the translocation may initiate the leukemic process, critical se condary genetic events are currently believed to be pivotal for leukemogene sis. We investigated 12 cases of childhood ALL with TEL/AML1 gene fusion by fluorescence in situ hybridization (FISH) and comparative genomic hybridiz ation (CGH) and documented additional or secondary genetic changes in seven patients (58%). Three patients showed extra copies of chromosome 21 includ ing a case in which the trisomy 21 (+21) clone was distinct from the one ha rboring TEL/AML1 gene fusion. Interestingly, one patient without +21 showed amplification of the AML1 gene on chromosome 21q, supporting the contentio n that AML1 amplification may be an important additional genetic event. Gen e expression study by semi-quantitative reverse-transcription polymerase ch ain reaction (RT-PCR) in two of these four patients showed an increase in A ML1 transcripts that paralleled the increase in gene copy number. Deletion of the normal TEL allele was detected in two patients, with one of them sho wing loss of chromosome 12 together with duplication of the der(12)t(12;21) . Finally, one patient showed duplication of the fusion signal. Our finding s confirm that additional or secondary genetic changes including AML1 ampli fication are commonly encountered in childhood ALL with TEL/AML1 gene fusio n, which are envisaged to play significant roles in disease progression.