The TAL-1 gene Is abnormally expressed and/or rearranged in a high percentage of T cell acute leukemias (T-ALL). Its product is a basic helix-loophelix (bHLH) transcription factor (TF), which heterodimerlzes with members of the Eprotein bHLH TF gene products. We have previously demonstrated the role of tal-1 in normal human erythropoiesis (G.L. Condorelli. et al.. Blood, 1995). However, the oncogenetic role of tal-1 ts still debated. We have tested the oncogenetic potential of tal-1 in a transgene mouse model: abnormal, lymphoid-restricted tal-1 expression Induces a perturbation in T-cell development and an Increase in mortality due to T and B lymphoid tumors In diverse cell lines of myeloid (HL-60, 32D) or non-hematopoietic (SAOSZ T98G) type ectoplc expression of the transduced TAL-1 gene stimulates growth under low serum conditions; furthermore, tal-1 blocks retlnoic acid and vitamin D3induced differentiation in HL-60 cells and G-CSF-mediated differentiation in 32D cells Finally, hematopoietic progenitor cells (HPCs), purified from normal adult peripheral blood and retrovirally transduced with the TAL-1 gene, exhibit enhanced erythroid and reduced. GM colony formation, in terms of both colony number and size. These results indicate the oncogenetic role of tal-1 in the pathogenesis of T-ALL and show that ectopic tal-1 expression causes enhanced cefl proliferation and differentiation blockade, particularly in myeloid cell models.
|Number of pages||1|
|Publication status||Published - 1996|
ASJC Scopus subject areas
- Cancer Research
- Cell Biology