Novel AML1 and AML1-ETO targets in Hematopoiesis

Scripps Research Institute, La Jolla CA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): AML1 is a key transcription factor during hematopoietic differentiation. It is fused to various cellular proteins as a result of chromosomal translocations found in myelogenous leukemia. The best-characterized fusion involving AML1 is the AML1-ETO protein that results from t (8; 21) in patients with acute myeloid leukemia. AML1 and AML1-ETO have identical N-terminal DNA binding domains but distinct C-terminal regions. The unique C-terminal regions of AML1 and AML1-ETO may regulate interactions with DNA and other transcription factors to alter the transcriptional activity of each protein. The hypothesis of this study is that AML1 and AML1-ETO not only regulate the same genes, but also a unique set of genes because of their distinct C-termini. Therefore, the goal of this proposal is to identify novel shared and distinct AML1 and AML1-ETO target genes that regulate hematopoiesis by using chromatin immunoprecipitation coupled to microarray analysis. The identification and characterization of target gene function should provide insight into how AML1 and AML1-ETO are involved in hematopoiesis and leukemogenesis. [unreadable] [unreadable] [unreadable]