Promoter analysis of TFPT (FB1), a molecular partner of TCF3 (E2A) in childhood acute lymphoblastic leukemia

We previously identified the TFPT (FB1) gene as a molecular partner of TCF3 (E2A) in childhood pre-B cell acute lymphoblastic leukemia (ALL). TFPT (FB1) alignment in man, mouse and rat displays a very high degree of identity, indicating that it may play a basic role in mammalian cells. To get insights into this role, we have identified and studied the TFPT (FB1) promoter and its responsiveness to hematopoietic transcriptional factors. We found that the TFPT (FB1) 5' flanking sequence displays the features of a TATA-less promoter with weak homology to Inr (Initiator) elements. Starvation experiments suggested that TFPT (FB1) expression might be constitutive. Nevertheless, the TFPT (FB1) promoter, tested by transactivation assays, was found to be responsive to Ikaros 2 and, mainly, to PU.1, a transcription factor belonging to the Ets family. Thus, these hematopoietic factors, known to play critical roles during the early stages of B cell differentiation and to be involved in leukemia, might modulate TFPT (FB1) expression during hematopoiesis and/or leukemia development.