Acute lymphoblastic leukemias that bear chromosomal translocations at 11q23 possess rearrangements of the Mixed Lineage Leukemia gene (MLL, HRX, ALL-1) and have a poor prognosis. Both i n f a nt leukemia and secondary leukemias following therapy with DNA topoisomerase II inhibitors frequently bear MLL translocations. This project will utilize genetic models and RNA profiling to determine the function and the critical target genes of Mll. A series of selected loss-of-function models of Mll in distinct hematopoietic lineages will reveal the normal roles of Mll, enable the profiling of Hox expression and discover additional targets using DNA microarray technology. The gene expression program controlled by Mll in murine hematopoietic cells will then be compared to the program of gene expression in Mll-fusion containing hematopoietic cells and murine Mll- dependent leukemia. In collaboration with Todd Golub, we will determine the expression profile of poor prognosis MLL-dependent human leukemia as it compares to that of more favorable prognosis leukemia. Comparison of the expression profiles from human and murine leukemia with that of Mll null hematopoietic lineages should help direct us to the genes regulated by Mll that are important in leukemogenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08CA092551-03
Application #
6613432
Study Section
Subcommittee G - Education (NCI)
Program Officer
Lohrey, Nancy
Project Start
2001-07-03
Project End
2006-06-30
Budget Start
2003-01-15
Budget End
2003-12-31
Support Year
3
Fiscal Year
2003
Total Cost
$132,759
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
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