Aberrantly regulated genes in TEL/AML1 positive leukaemia

TEL/AML1 is the most common chromosomal rearrangement in pediatric cancer, occurring in approximately 25% of acute lymphoblastic leukaemia (ALL). To reveal the molecular mechanisms underlying the pathogenesis of this disease, we have generated gene expression profiles from two patients with this rearrangement using serial analysis of gene expression. We sequenced a total of 72.000 tags. Libraries were compared to existing gene expression profiles of normal B cells covering major steps of B cell development that have previously been generated (Feldhahn et. al. 2002 PNAS). In addition, we compared the data to existing profiles of BCR/ABL- and MLL/AF4-positive cases, in order to identify the molecular correlate of the particularly favourable outcome of patients suffering from leukaemia with TEL/AML1 rearrangement.

The majority of genes that displayed differential expression in these entities clustered into groups involved in B-cell receptor signalling, cell cycle control, apoptosis and regulation of gene transcription. To corroborate quantitative differences in gene expression, semiquantitative RT-PCR analysis is currently performed on the set of identified candidate genes.

U.H. was Supported by a greed of the José-Carreras-Stiftung