Hematological malignancies as well as many solid tumors harbor sub-populations of tumor-initiating cells that are important for tumor onset, progression, and malignancy. These multipotent tumor-initiating cells have the ability to proliferate and self-renew and are highly resistant to conventional chemotherapy and radiotherapy. In this proposal, we hypothesize that drug-resistant tumor-initiating cells exist in human mantle cell lymphoma (MCLs), and that they have the capacity to initiate the formation and progression of MCLs. MCL is aggressive B cell lymphoid malignancy and patients with MCL have median survival of two or three years. Conventional chemotherapy and radiation regimens are not curative for advanced MCL. The highly aggressive clinical behavior and low survival rates make MCL an ideal model for identification and characterization of tumor-initiating cells. Characterization of clonogenic populations that initiate MCL tumor formation will enable us to probe the pathology of these cells during tumor initiation and progression. These efforts may help the development of new preclinical models as well as the design of novel therapeutic strategies to treat or prevent the pathogenesis of MCLs in humans.

Public Health Relevance

Non-Hodgkin's lymphomas (NHL) are the fifth most common cancer in the United States and the incidence of NHL has nearly doubled during the past three decades. However, cells initiating lymphoma have not been found. Therefore, we will use mantle cell lymphoma as a model to identify cells initiating proliferation of tumor cells and sustain tumor growth.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA141275-02
Application #
7992452
Study Section
Molecular Oncogenesis Study Section (MONC)
Program Officer
Howcroft, Thomas K
Project Start
2009-12-01
Project End
2012-11-30
Budget Start
2010-12-01
Budget End
2012-11-30
Support Year
2
Fiscal Year
2011
Total Cost
$189,878
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
Chen, Zheng; Romaguera, Jorge; Wang, Michael et al. (2012) Verapamil synergistically enhances cytotoxicity of bortezomib in mantle cell lymphoma via induction of reactive oxygen species production. Br J Haematol 159:243-6
Jung, Hyun Joo; Chen, Zheng; McCarty, Nami (2012) Synergistic anticancer effects of arsenic trioxide with bortezomib in mantle cell lymphoma. Am J Hematol 87:1057-64
Jung, Hyun Joo; Chen, Zheng; Fayad, Luis et al. (2012) Bortezomib-resistant nuclear factor ?B expression in stem-like cells in mantle cell lymphoma. Exp Hematol 40:107-18.e2
Jung, Hyun Joo; Chen, Zheng; McCarty, Nami (2011) Stem-like tumor cells confer drug resistant properties to mantle cell lymphoma. Leuk Lymphoma 52:1066-79
Chen, Zheng; Ayala, Paul; Wang, Michael et al. (2010) Prospective isolation of clonogenic mantle cell lymphoma-initiating cells. Stem Cell Res 5:212-25