TEL/AML-1 fusion gene: its frequency and prognostic significance in childhood acute lymphoblastic leukemia

TEL gene rearrangement due to the 12;21 chromosome translocation is believe d to be the most common molecular genetic abnormality in childhood acute ly mphoblastic leukemia (ALL). A study was conducted to investigate the freque ncy and prognostic significance of TEL/AML-1 fusion gene resulting from a c ryptic t(12;21)(p13;q22). Bone marrow samples from 86 patients diagnosed ov er the past 5 years at Columbus Children's Hospital were analyzed by fluore scence in situ hybridization (FISH) technique for TEL/AML-1 fusion gene, us ing LSI(R) DNA probes. The positive cases were analyzed for clinical outcom e. Patients in this study received treatment according to Children's Cancer Group (CCG) protocols. Fifteen of the 86 cases (17%) were positive for the fusion gene. All were B-cell lineage and except for one, all were CD10 pos itive. TEL/AML-1 was not found in any T-cell ALL. The mean overall survival (OS) following diagnosis for the TEL/AML-1-positive group was significantl y longer than for the TEL/AML-1-negative group by log-rank = 7.83, P = 0.00 5. Similarly, the event-free survival (EFS) after remission for the positiv e group (median 94.5 months) was longer than the negative group (median 57 months) by log-rank = 7.19, P = 0.007, This study confirms that the TEL/AML -1 fusion gene may be the most common genetic event in childhood ALL, occur ring in 17% of the patients. It appears restricted to the B-cell lineage, I n this study, the presence of a TEL/AML-1 fusion gene was statistically sig nificant in predicting both OS and EFS, indicating a favorable clinical out come for these patients. Screening for TEL/AML-1 should become routine at d iagnosis and a useful biological variable for risk stratification in future clinical trials. (C) 2000 Elsevier Science Inc. All rights reserved.