The role of a transcription factor LYL1 in leukemogenesis

A number of transcription factors were revealed in the study of chromosomal translocation associated with T cell acute lymphoblastic leukemia. LYL1 is one of the examples of such transcription factors. LYL1 is a member of the class II basic helix-loop-helix transcription factors and aberrantly expressed in a fraction of human T cell acute lymphoblastic leukemia. The mechanism of leukemogenesis by LYL1 has been studied in transgenic mouse ubiquitously overexpressing LYL1 using a construct expressing full-length cDNA driven by a human elongation factor 1α promoter. 30% of these transgenic mice developed malignant lymphoma with an average latent period of 352 days. Lymphomas developed are both B and T cell lymphomas. LYL1 forms a heterodimer with another basic helix-loop-helix protein E2A. Overexpressed LYL1 inhibits the E2A/HEB heterodimer formation, thus inactivates the physiological function of E2A, which might be the essential step to leukemogenesis