Fluorescence in situ hybridization study of TEL/AML1 fusion and other abnormalities involving TEL and AML1 genes. Correlation with cytogenetic findings and prognostic value in children with acute lymphoblastic leukemia

Background and Objectives. The TEL/AML1 fusion is the most common genetic a bnormality found in childhood acute lymphoblastic leukemias (ALL). Although it is very difficult to identify by conventional cytogenetic techniques it can be readily detected using fluorescence in situ hybridization (FISH). W e carried out cytogenetic and FISH studies on 42 children with ALL in order to know the frequency of this translocation in our population, the inciden ce of TEL and/or AML1 gene alterations, and their correlation with clinical evolution and prognosis. In addition, we performed reverse transcription p olymerase chain reaction (RT-PCR) in some cases, confirming the feasibility of FISH techniques in the detection of this translocation. Design and Methods. Bone marrow samples were obtained from 42 childhood ALL patients. The copy number of AML1 and TEL genes were studied using fluores cent in situ hybridization with a dual color DNA probe specific for the AML 1 and TEL genes. Results. We found a frequency of TEL/AML1 fusion of 17% in our sample, Doub le TEL/AML1 fusion, lack of TEL signal and extra AML1 signals were frequent additional FISH abnormalities. Duplication of a chromosomal complement, de letion of chromosome 12p arm, and polysomies of chromosome 21 are plausible explanations for these additional FISH findings. However, a relatively hig h proportion of our cases (9.5%) presented specific amplification of AML1. A statistically significant difference in prognosis was found between patie nts with and without these additional AML1 or TEL FISH alterations (p<0.02) , which could be related to the presence of specific karyotypes. Interpreta tions and Conclusions. The frequency of TEL/AML1 fusion is similar to that found in o ther populations (17%). We found that FISH analysis of AML and TEL is relat ed to the evolution of the disease. The absence of alterations in these gen es revealed by FISH could be indicative of bad prognosis, while the presenc e of alterations is related to a good evolution. Our results suggest that i nterphase FISH analysis to search for alterations in AML and TEL genes coul d be extremely useful for complementing cytogenetic studies and for providi ng additional information about the possible outcome of the disease in pati ents with ALL. (C) 2001, Ferrata Storti Foundation.