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 (FB 1) 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 insigh ts into this role, we have identified and studied the TFPT (FB1) promoter a nd its responsiveness to hematopoietic transcriptional factors. We found th at the TFPT (FB1) 5' flanking sequence displays the features of a TATA-less promoter with weak homology to Inr (Initiator) elements. Starvation experi ments suggested that TFPT (FB1) expression might be constitutive. Neverthel ess, the TFPT (FB1) promoter, tested by transactivation assays, was found t o be responsive to Ikaros 2 and, mainly, to PU.1, a transcription factor be longing 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 hematopo iesis and/or leukemia development. (C) 2001 Academic Press.