Abstract

We intend to define the genetic changes that are responsible for the pathogenesis of B-CLL and to correlate such changes to the clinical behavior of the leukemia and its response to treatment. The project has four specific aims that form the different genetic changes responsible for B-CLL initiation and progression. 1) We intend to define the role of CLL1, a novel putative tumor suppressor gene, in the pathogenesis of B-CLL and in the response to treatment. 2) We intend to determine the role of HMGI-G in the progression of B- CLL and whether self fusion of HMGI3 is involved in the development of CLL with trisomy of chromosome 12 or a normal karyotype. 3) We intend to determine whether the FHIT gene at 3p14.2 plays a role in the progression of B-CLL, and 4) We intend to determine whether the ATM and CLL1 genes play a role in the pathogenesis of familial CLL. The achievement of these goals will revolutionize our understanding of the mechanisms involved in the pathogenesis of B-CLL and will provide the basis for new approaches to the treatment of B-CLL.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
3P01CA081534-02S1
Application #
6485524
Study Section
Subcommittee E - Prevention &Control (NCI)
Project Start
2000-05-01
Project End
2001-04-30
Budget Start
Budget End
Support Year
2
Fiscal Year
2001
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

Barr, Paul M; Robak, Tadeusz; Owen, Carolyn et al. (2018) Sustained efficacy and detailed clinical follow-up of first-line ibrutinib treatment in older patients with chronic lymphocytic leukemia: extended phase 3 results from RESONATE-2. Haematologica 103:1502-1510
Kondo, K; Shaim, H; Thompson, P A et al. (2018) Ibrutinib modulates the immunosuppressive CLL microenvironment through STAT3-mediated suppression of regulatory B-cell function and inhibition of the PD-1/PD-L1 pathway. Leukemia 32:960-970
Hasan, Md Kamrul; Yu, Jian; Widhopf 2nd, George F et al. (2018) Wnt5a induces ROR1 to recruit DOCK2 to activate Rac1/2 in chronic lymphocytic leukemia. Blood 132:170-178
Ten Hacken, Elisa; Valentin, Rebecca; Regis, Fara Faye D et al. (2018) Splicing modulation sensitizes chronic lymphocytic leukemia cells to venetoclax by remodeling mitochondrial apoptotic dependencies. JCI Insight 3:
Gribben, John G (2018) How and when I do allogeneic transplant in CLL. Blood 132:31-39
Sivina, Mariela; Werner, Lillian; Rassenti, Laura et al. (2018) Dynamic changes in CCL3 and CCL4 plasma concentrations in patients with chronic lymphocytic leukaemia managed with observation. Br J Haematol 180:597-600
Ott, Christopher J; Federation, Alexander J; Schwartz, Logan S et al. (2018) Enhancer Architecture and Essential Core Regulatory Circuitry of Chronic Lymphocytic Leukemia. Cancer Cell 34:982-995.e7
Balatti, Veronica; Tomasello, Luisa; Rassenti, Laura Z et al. (2018) miR-125a and miR-34a expression predicts Richter syndrome in chronic lymphocytic leukemia patients. Blood 132:2179-2182
Vangapandu, Hima V; Chen, Huiqin; Wierda, William G et al. (2018) Proteomics profiling identifies induction of caveolin-1 in chronic lymphocytic leukemia cells by bone marrow stromal cells. Leuk Lymphoma 59:1427-1438
Yu, Jian; Chen, Yun; Chen, Liguang et al. (2018) Cirmtuzumab inhibits ibrutinib-resistant, Wnt5a-induced Rac1 activation and proliferation in mantle cell lymphoma. Oncotarget 9:24731-24736

Showing the most recent 10 out of 562 publications