TAL1 expression does not occur in the majority of T-ALL blasts

The TALI gene is disrupted by translocation or deletion (tal(d)) in up to 30% of T-cell acute lymphoblastic leukaemia (T-ALL), leading to aberrant transcriptional activation, as a SIL-TAL1 fused transcript in tald, It has been suggested that TAL1 transcription occurs in approximately 50% of a T-ALLs without apparent rearrangement. SIL-TAL1 was positive in 15/60 (25%) of T-ALL, whereas wild-type TALI transcripts were detected in all 13 SIL-TAL1 and in 19/43 (44%) T-ALL without SIL-TAL1. To investigate the cellular origin of TALI we exploited the fact that GATA1 and TALI are co-ordinately expressed in non-lymphoid haemopoietic cells, whereas only the latter is found in TALL. GATA1 was detected in 10/23 (43%) TALI-negative ALLs but in 17/19 (89%) 'unexplained' TAL1-positive cases, suggesting a common non-lymphoid cellular origin. Immunocytochemical analysis with a TAL1-specific monoclonal antibody showed nuclear expression in the blasts of 10/34(29%) cases, including 8/10 SIL-TAL1(+) and two RT-PCR TAL1(+), SIL-TAL1(-) cases. In the remaining cases TAL1 expression was restricted to a minor population (< 5%) of larger, strongly TAL1-positive cells which comprised erythroid cells, CD34(+)CD3(-) precursors and an unidentified TAL1(+)CD45(-) population which morphologically resembled monocytes/macrophages. We therefore suggest that appropriate diagnostic evaluation of T-ALL should include molecular detection of SIL-TAL1 transcripts and in situ immunocytochemical detection of TAL1 protein expression by leukaemic blasts. This approach will enable accurate analysis of the prognostic significance of TAL1 deregulation in T-ALL.