THE ONCOGENIC T-CELL LIM-PROTEIN LMO2 FORMS PART OF A DNA-BINDING COMPLEX SPECIFICALLY IN IMMATURE T-CELLS

The LIM-only protein LMO2 is expressed aberrantly in acute T-cell leuk aemias as a result of the chromosomal translocations t(11;14) (p13;q11 ) or t(7;11) (q35;p13). In a transgenic model of tumorigenesis by Lmo2 , T-cell acute leukaemias arise after an asymptomatic phase in which a n accumulation of immature CD4(-) CD8(-) double negative thymocytes oc curs. Possible molecular mechanisms underlying these effects have been investigated in T cells from Lmo2 transgenic mice. Isolation of DNA-b inding sites by CASTing and band shift assays demonstrates the presenc e of an oligomeric complex involving Lmo2 which can bind to a bipartit e DNA motif comprising two E-box sequences similar to 10 bp apart, whi ch is distinct from that found in erythroid cells. This complex occurs in T-cell tumours and it is restricted to the immature CD4(-) CD8(-) thymocyte subset in asymptomatic transgenic mice. Thus, ectopic expres sion of Lmo2 by transgenesis, or by chromosomal translocations in huma ns, may result in the aberrant protein interactions causing abnormal r egulation of gene expression, resulting in a blockage of T-cell differ entiation and providing precursor cells for overt tumour formation.