The Identification of (ETV6)/RUNX1-Regulated Genes in Lymphopoiesis Using Histone Deacetylase Inhibitors in ETV6/RUNX1-Positive Lymphoid Leukemic Cells

摘要: Purpose: Chimeric transcription factor ETV6/RUNX1 (TEL/AML1) is believed to cause pathologic block in lymphoid cell development via interaction with corepressor complex and histone deacetylase. We wanted show the regulatory effect of its reversibility by deacetylase inhibitors (HDACi), as well identify potential ETV6/RUNX1-regulated genes. Experimental Design: used luciferase assay protein, gene, HDACi. To genes, we expression profiling HDACi cells. Next, using flow cytometry quantitative reverse transcription-PCR, measured differentiation changes gene protein after treatment. Results: Luciferase showed repression granzyme B this Proving role ETV6/RUNX1, identified, statistical analysis, 25 genes that are potentially regulated protein. In four selected known cycle regulation ( JunD, ACK1, PDGFRB , TCF4 ), confirmed analysis. After treatment, ETV6/RUNX1-positive cells immunophenotype resembling process compared other leukemic (BCR/ABL, ETV6/PDGFRB positive). Moreover, accumulated G1-G phase whereas B-lineage lines rather unspecific including induction apoptosis decreased proliferation. Conclusions: Presented data support hypothesis affect direct treatment may release aberrant activity caused chimeric factor.