The importance of the bone marrow environment in regulating normal hematopoiesis is well established, but its contribution to myeloid leukemogenesis remains largely undefined. Cell-cell and cell-extracellular matrix interactions within the bone marrow are critical control events that constitute potential targets for leukemogenesis. The proposed aims are to explore the molecular mechanisms of stromal signalling in hematopoietic cells and the disorders of these mechanisms in acute myeloid leukemia. The expression of aminopeptidase N/CD13 (APN) on the myeloid cell surface is regulated by stromal cell contact, with the involvement of myb/ets factors. APN expression is also uniquely reduced in leukemias with the t(8;21) translocation--a lesion that generates a chimeric regulatory protein AML-ETO. The Investigator proposes that AML-ETO interferes with normal AML-1 signalling to the myb/ets-APN pathway, thus blocking APN expression. The two specific aims are designed to define the specific signals generated by the interaction of myeloid cells and stromal cells, focussing on the myb ets pathway, and to assess the impact of AML-ETO on the myb ets-APN pathway.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA070909-02
Application #
2390936
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1996-04-01
Project End
2001-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
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