Abstract

By using the positional cloning approach we propose to identify and characterize the genes that are involved in the initiation and progression of B-CLL. We will focus on region 13q14, that is often involved in loss of heterozygosity (LOH) in B-CLL and on region 11q23 that is involved in loss of heterozygosity in B-CLLs that have progressed to a much more aggressive phenotype. By carrying out loss of heterozygosity studies at 13q14 we have identified the minimal region of loss that is involved in the majority of B-CLLs. We propose to clone and characterize the gene within this region that is mutated or deleted in the majority of B-CLLs. For this purpose we have sequenced the entire region of 550kb and we are in the process of investigating this region for the presence of transcribed genes that are mutated and/or deleted in CLL. Recently we have discovered mutations of the ATM gene in B CLLs, that have progressed to a much more aggressive phenotype. We propose to define the role of the ATM gene in the progression of B-CLL.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory Grants (P20)
Project #
1P20CA081534-01
Application #
6259043
Study Section
Subcommittee G - Education (NCI)
Project Start
1999-05-01
Project End
2000-04-30
Budget Start
Budget End
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Veronese, A; Pepe, F; Chiacchia, J et al. (2015) Allele-specific loss and transcription of the miR-15a/16-1 cluster in chronic lymphocytic leukemia. Leukemia 29:86-95
Maji, Santanu; Samal, Sabindra K; Pattanaik, Laxmipriya et al. (2015) Mcl-1 is an important therapeutic target for oral squamous cell carcinomas. Oncotarget 6:16623-37
Wu, Bainan; Barile, Elisa; De, Surya K et al. (2015) High-Throughput Screening by Nuclear Magnetic Resonance (HTS by NMR) for the Identification of PPIs Antagonists. Curr Top Med Chem 15:2032-42
Wu, Bainan; Wang, Si; De, Surya K et al. (2015) Design and Characterization of Novel EphA2 Agonists for Targeted Delivery of Chemotherapy to Cancer Cells. Chem Biol 22:876-887
Lamothe, Betty; Cervantes-Gomez, Fabiola; Sivina, Mariela et al. (2015) Proteasome inhibitor carfilzomib complements ibrutinib's action in chronic lymphocytic leukemia. Blood 125:407-10
Laganà, Alessandro; Acunzo, Mario; Romano, Giulia et al. (2014) miR-Synth: a computational resource for the design of multi-site multi-target synthetic miRNAs. Nucleic Acids Res 42:5416-25
McClanahan, Fabienne; Gribben, John (2014) Transplantation in chronic lymphocytic leukemia: does it still matter in the era of novel targeted therapies? Hematol Oncol Clin North Am 28:1055-71
Vamos, Mitchell; Welsh, Kate; Finlay, Darren et al. (2013) Expedient synthesis of highly potent antagonists of inhibitor of apoptosis proteins (IAPs) with unique selectivity for ML-IAP. ACS Chem Biol 8:725-32
Hudson, Robert S; Yi, Ming; Volfovsky, Natalia et al. (2013) Transcription signatures encoded by ultraconserved genomic regions in human prostate cancer. Mol Cancer 12:13
Balakrishnan, Kumudha; Gandhi, Varsha (2013) Bcl-2 antagonists: a proof of concept for CLL therapy. Invest New Drugs 31:1384-94

Showing the most recent 10 out of 46 publications