RT PCR DETECTION OF SIL-TAL-1 FUSION MESSENGER-RNA IN CHINESE T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA (T-ALL)/

The TAL-1 gene is located on chromosome 1p32. In about 20% of T-cell a cute 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' p art of the sn 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 transcript ional expression. A chimeric mRNA was observed in four of 17 T-ALL cas es and hats 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 pro cedure could detect one leukemic cell among 10(6) normal cells. A posi tive RT/PCR result was obtained in two cases during clinical remission , suggesting the presence of minimal residual disease (MRD). One patie nt developed clinical relapse 3 months after PCR positivity. Moreover, analysis of the Tal(d) rearrangement by DNA-based PCR in four patient s with SIL-TAL-1 fusion revealed the type A (Tal(d1)) rearrangement in all cases. Sequence analysis demonstrated the presence of N region an d non-random ''P'' neucleotide, os well as bose deletions at the genom ic 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.