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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL079900-02
Application #
6934568
Study Section
Special Emphasis Panel (ZRG1-F09 (20))
Program Officer
Werner, Ellen
Project Start
2004-07-01
Project End
2006-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
2
Fiscal Year
2005
Total Cost
$49,928
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Yan, Ming; Kanbe, Eiki; Peterson, Luke F et al. (2006) A previously unidentified alternatively spliced isoform of t(8;21) transcript promotes leukemogenesis. Nat Med 12:945-9