T-cell leukemia, including T-lineage acute lymphoblastic leukemia, is among the most common and aggressive form of hematologic malignancy in both children and adults. This malignancy represents a heterogeneous group of lymphoid cancers with varied morphologic and immunologic features of transformed T-cells originated from normal T-cell precursors. Syk, a non-receptor tyrosine kinase, plays critical roles in cell signaling events mediated by hematopoietic receptors such as T-cell receptor. Interestingly, expression of Syk inhibits human breast cancer cell growth and metastasis, perhaps by suppressing malignant growth of the breast cancer cells. Like in breast cancer cells, Syk expression is reduced in T-lineage leukemia cells. Our previous studies have demonstrated that expression of Syk in leukemic T-cells inhibits the proliferation and activation-induced-cell-death of these cells. The working hypothesis of the candidate's dissertation project is that expression of an activated Syk can control the growth and tumorigenicity of T-lineage leukemia cells. My study will test this hypothesis using both in vitro analyses and in vivo animal studies to determine the molecular and cellular mechanisms of how Syk expression may regulate the growth of leukemic T-cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31CA117055-05
Application #
7660492
Study Section
Special Emphasis Panel (ZRG1-IDM-P (29))
Program Officer
Bini, Alessandra M
Project Start
2005-08-01
Project End
2010-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
5
Fiscal Year
2009
Total Cost
$26,091
Indirect Cost
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
Ortiz, Serina; Lee, Wenhui; Smith, David et al. (2010) Comparative analyses of differentially induced T-cell receptor-mediated phosphorylation pathways in T lymphoma cells. Exp Biol Med (Maywood) 235:1450-63