RT/PCR detection of SIL-TAL-1 fusion mRNA in Chinese T-cell acute lymphoblastic leukemia (T-ALL).

The TAL-1 gene is located on chromosome 1p32. In about 20% of T-cell acute lymphoblastic leukemias (T-ALL), this gene is disrupted in its 5' portion by a site-specific 100-kg deletion and is fused with the 5' part of the SIL gene, to form SIL-TAL-1 chimeric gene. In this study, we established a "nested" retrotranscriptase/polymerase chain reaction (RT/PCR) technique which allows detection of the SIL-TAL-1 transcriptional expression. A chimeric mRNA was observed in four of 17 T-ALL cases and has been shown to result from the fusion between the exon 1 of SIL and exon 3 of TAL. A sensitivity test showed that this RT/PCR procedure could detect one leukemic cell among 10(6) normal cells. A positive RT/PCR result was obtained in two cases during clinical remission, suggesting the presence of minimal residual disease (MRD). One patient developed clinical relapse 3 months after PCR positivity. Moreover, analysis of the Tald rearrangement by DNA-based PCR in four patients with SIL-TAL-1 fusion revealed the type A (Tald1) rearrangement in all cases. Sequence analysis demonstrated the presence of N region and non-random "P" nucleotide, as well as base deletions at the genomic SIL-TAL-1 joining site. These data indicate that detection of TAL-1 gene abnormality is important for diagnosis and monitoring of MRD in a subset of T-ALL.