TRANSCRIPTIONAL ACTIVITY OF TAL1 IN T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA (T-ALL) REQUIRES RBTN1 OR RBTN2 AND INDUCES TALLA1, A HIGHLY SPECIFIC TUMOR-MARKER OF T-ALL

TAL1, which is frequently activated in T cell acute lymphoblastic leuk emia (T-ALL), encodes lineage-specific basic helix-loop-helix (bHLH) p roteins that bind specifically to E-box DNA motif upon dimerization wi th ubiquitous basic helix-loop-helix proteins E47 or E12, RBTN1 and RB TN2, also frequently activated in T-ALL, encode proteins only with tan dem cysteine-rich LIM domains, We found that aberrant expression of TA L1 detected in 11 out of 14 T-ALL cell lines was invariably accompanie d by that of either RBTN1 or RBTN2, Forced expression of TAL1 together with RBTN1 or RBTN2, but not TAL1 alone, strongly induced artificial reporter genes in a TAL1/RBTN-negative T-ALL cell Line, HPB-ALL, Such collaborative transcriptional activity of TAL1 and RBTN was not, howev er, observed in non-T cell lines, suggesting further involvement of so me T cell-specific cofactors. In this context, we carried out prelimin ary evaluation of a potential role of the T cell-specific GATA-binding protein, GATA3, in the transcriptional activity of TAL1 and RBTN. We also showed that coexpression of TAL1 and RBTN1 in HPB-ALL strongly in duced TALLA1, a highly specific T-ALL marker whose positivity correlat ed 100% with ectopic expression of TAL1 among various T-ALL cell lines , Collectively, ectopic TAL1 and RBTN1 or -2, together with some endog enous T cell-specific cofactors like GATA3, constitute a highly collab orative set of transcription factors whose aberrant activity in T cell s may lead to leukemogenesis by modulating expression of downstream ge nes such as TALLA1.