Growth inhibition and apoptosis due to restoration of E2A activity in T cell acute lymphoblastic leukemia cells

Two models have been proposed for die molecular mechanism by which the Tall oncogene causes T cell acute lymphoblastic leukemia (T-ALL). The activatio n model suggests that Tall as heterodimers with the E2A transcription facto r activates the expression of oncogenes. The inhibition model postulates th at Tall interferes with the tumor-suppressing function of E2A. In the Jurka t T cell line, originally derived from a patient with T-ALL, Tall is comple xed with E2A proteins and the transcriptional activity of E2A is very low. When E2A activity was restored by expressing an E2A-Tal1 fusion protein, E- T/2, the Jurkat cells underwent growth arrest and subsequently apoptosis, t hus supporting the inhibition model and suggesting that E2A loss may contri bute to leukemic progression.