The objectives of this application are to continue our studies on the control of proliferation and differentiation in human, non- Hodgkin's B cell lymphomas (NHL-B). Since we have shown that BCGF-like lymphokine growth factors are important molecules in controlling growth factors in these tumors, particularly in the most aggressive forms of NHL-B, it is of particular importance to establish the biochemical nature of the autocrine BCGF-like molecules, which we believe are responsible for the autonomous rapid cell growth characteristic of these lymphomas.
The specific aims of this proposal seek to: (1) characterize the nature of the BCGF-like autocrine growth factor molecules in detail by biochemical purification, affinity chromatography with polyclonal anti BCGF antibodies; peptide-mapping of the growth factor, followed by NH2-terminal AA sequence analysis. Further studies will then attempt to clone the gene for this molecule(s) using oligonucleotide probes, and cDNA libraries constructed from the tumor cells. (2) The receptors for the growth factor molecules on NHL-B will be identified, characterized and their regulation studied with regard to the control of tumor cell growth. (3) The genes involved in the production of autocrine BCGF-like growth factors by NHL-B will be studied using cloned probes for the natural product BCGF, usually expressed in activated T cells, to determine the relationship between the neoplastic and normal growth factors, as well as control mechanisms involved in the respective gene expressions. (4) The role of differentiation in the NHL-B will be explored to determine the cause as well as the effect of blocks in B cell differentiation on the biology of the NHL-B. These functional studies will hopefully contribute to the further development of biologic response modification (BRM) therapy for these diseases in the forseeable future.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA031479-08
Application #
3169594
Study Section
Pathology B Study Section (PTHB)
Project Start
1982-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
Hospitals
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
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Rodriguez, M A; Ford, R J; Goodacre, A et al. (1991) Chromosome 17- and p53 changes in lymphoma. Br J Haematol 79:575-82
Ford, R J; Goodacre, A; Ramirez, I et al. (1990) Establishment and characterization of human B-cell lymphoma cell lines using B-cell growth factor. Blood 75:1311-8
Donehower, L A; Bohannon, R C; Ford, R J et al. (1990) The use of primers from highly conserved pol regions to identify uncharacterized retroviruses by the polymerase chain reaction. J Virol Methods 28:33-46
Sahasrabuddhe, C G; Sekhsaria, S; Yoshimura, L et al. (1989) Isolation and characterization of growth factor(s) from a human B-cell lymphoma. Blood 73:1149-56
Ford, R J; Rajaraman, C; Lu, M et al. (1988) In vitro analysis of cell populations involved in Hodgkin's disease lesions and in the characteristic T cell immunodeficiency. Hematol Oncol 6:247-55
Sahasrabuddhe, C G; Sekhsaria, S; Martin, B et al. (1988) Human B cell growth factor and neoplasia. Prog Clin Biol Res 262:269-82
Ford, R J; Mehta, S; Sharma, S (1987) In vitro studies on leukemia cells and T lymphocytes in hairy cell leukemia. Leukemia 1:386-9
Sharma, S; Mehta, S R; Ford, R J (1987) Growth factor, viruses, and oncogenes in human lymphoid neoplasia. Lymphokine Res 6:245-65
Ford, R J; Kwok, D; Quesada, J et al. (1986) Production of B cell growth factor(s) by neoplastic B cells from hairy cell leukemia patients. Blood 67:573-7

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