Anaplastic Large Cell Lymphoma (ALCL) comprises 10% of all non-Hodgkin's lymphoma. ALCL are uniformly CD30 (+) and 50-60% of ALCL are characterized by the t (2;5) translocation which produces a fusion protein between Nucleophosmin on chromosome 5 and Anaplastic Lymphoma Kinase (ALK) on chromosome 2. NPM-ALK is an oncogenic tyrosine kinase that activates multiple signal transduction pathways. A number of NPM-ALK (+) cell lines have been shown to undergo growth arrest when CD30 is activated. The goal of this proposal is to: 1) determine which signaling pathways are critical for transformation, and 2) determine how CD30 modulates NPM-ALK pathways. To accomplish these goals the applicant will: 1) Determine how NPM-ALK activates PI3K and the STATs, 2) Determine the role of PLC-?, PI3-kinase, STATs and scaffolding proteins in NPM-ALK induced lymphomagenesis in a murine bone marrow transplant model, 3) Determine the mechanism by which CD30 modulates NPM-ALK signaling pathways. These studies will provide valuable insight into the biology of NPM-ALK (+) lymphomas that may lead to new therapeutic modalities. The candidate, who completed an academic Hematology-Oncology fellowship at Beth Israel Deaconess Medical Center, is committed to a career in academic medicine with an emphasis in translational research. The proposed five-year course of study will give the candidate a broad experience in fields of immunotherapy and signal transduction leaving him prepared to make the transition to independent investigator.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08CA096876-01
Application #
6522078
Study Section
Subcommittee G - Education (NCI)
Program Officer
Lohrey, Nancy
Project Start
2002-07-17
Project End
2007-06-30
Budget Start
2002-07-17
Budget End
2002-12-31
Support Year
1
Fiscal Year
2002
Total Cost
$65,165
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
Koon, Henry B; Ippolito, Gregory C; Banham, Alison H et al. (2007) FOXP1: a potential therapeutic target in cancer. Expert Opin Ther Targets 11:955-65