Advertisement

The Role of Growth Factors in Human Lymphomas

  • R. J. Ford
  • A. Tamayo
  • J. L. AmbrusJr.
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 182)

Abstract

Human lymphomas are a common, heterogeneous group (<20 types) of lymphoid neoplasms, primarily derived (<80%) from the B lymphocytic lineage[1]. While the B cell non-Hodgkin’s lymphomas (NHL-B), show a considerable morphologic spectrum of neoplastic B lymphocytes, the NHL-B are classified primarily on the basis of clinical behavior, into low, intermediate, and high grade lymphomas in the International Working Formulation (IWF) [2]. While this classification system is woefully inadequate scientifically and considerably out of date clinically, it does emphasize the point that NHL-B can be generally thought of as being either low grade (indolent) or high grade (aggressive), (with the gratuitous hedge of being “intermediate” for those lymphomas that do not quite fit into the extremes). This yin-yang type of clinical behavior correlates quite well with the proliferative potential of the various subtypes of lymphoma cells, suggesting a cause-effect relationship. This type of correlation also suggests that very different types of growth regulation is present in high vs. low grade NHL-B. A variety of arguments have been made for the role(s) of several protooncogenes in the dysregulation of growth control in these neoplasms. Activation and rearrangement of the myc proto-oncogene in high grade NHL-B (esp. Burkitt’s type) seems to be at least one factor in the prodigious growth potential of these cells, that may in fact be further potentiated by inactivation of the tumor suppressor gene p53, by point mutations or other mechanisms[3]. In the low grade NHL-B, the central importance of the bcl-2 proto-oncogene has been emphasized, due to its consistent association with the disease process in follicular lymphoma. While the exact mechanism for its apparent involvement in the development of follicular lymphoma is still obscure, the transgenic experiments suggest that abrogation of apoptosis mediated by bcl-2 expression in B lymphocytes may contribute to the pathogenesis[4]. Although a variety of studies have shown that cell kinetics play a role in the clinical behavior of the NHL-B, the biologic basis of growth regulation in these human lymphoid tumors is still obscure. Our basic hypothesis has been that malignant human B cells, which retain most of the immunophenotypic cell surface molecular characteristics of their normal B cell counterparts, retain the capacity to respond to the same or very similar cytokine growth factor signals[5]. Differences observed in the regulation of neoplastic B cell growth, relate at least in part to the presence of potential cellular sources (e.g. accessory immune cells, etc.) and subsequent availability of the growth factor(s) that control the proliferative potential of these tumors. Our studies[6] have shown that the only growth factors that show consistent stimulatory activity on NHL-B are the human B cell growth factors (BCGFs), as shown in Table 1. These cytokine growth factors, which are normally produced by activated human T lymphocytes, are also similar or identical to autocrine growth factors (AGF) produced by high grade NHL-B. While most of the early members of the Interleukin group of cytokines (IL1-7) have been reported to have at least some stimulatory activity on normal human B cells, most of these factors have subsequently been shown to preferentially stimulate various subsets of T cells or other non-lymphoid cells (e.g. IL-4 functions as a Mast cell growth factor) rather than human B lymphocytes (Table 2).

Keywords

Chronic Lymphocytic Leukemia Follicular Lymphoma Hairy Cell Leukemia Lymphoid Neoplasm High Grade Lymphoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Magrath IT (ed.) (1990) The Non-Hodgkin’s Lymphomas. Williams & Wilkens, Baltimore.Google Scholar
  2. 2.
    NCI Non-Hodgkin’s lymphoma classification project (1982), Cancer 49:2112–2135.CrossRefGoogle Scholar
  3. 3.
    Gaidano G, Ballerini P, Gong JZ, Neri A, Newcombe EW, Magrath IT, Knowles DM, Dalla-Favera R. (1991) p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. Proc Natl Acad Sci. (USA) 88:5413–5417.CrossRefGoogle Scholar
  4. 4.
    McDonnell TJ, Deane N, Platt F, Hockenbery D, London L, Mckeara JP, Korsmeyer SJ (1989) bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell 57: 79–88.PubMedCrossRefGoogle Scholar
  5. 5.
    Ford RJ, Kwok D, Quesada J, Sahasrabuddhe CG. (1986) Production of B cell growth factors by neoplastic B cells from hairy cell leukemia patients. Blood 67:573–577.PubMedGoogle Scholar
  6. 6.
    Ford RJ, Kouttab N, Sahasrabuddhe CG, Davis M, Mehta SR. (1985) Growth factor-mediated proliferation in B cell non-Hodgkin’s lymphomas. Blood 65:1335–1341.PubMedGoogle Scholar
  7. 7.
    Clayberger C, Lee JE, Pillai A, Campbell M, Levy R, Krensky AM. (1992) Interleukin 3 is a growth factor for human follicular B cell lymphoma. J Exp Med 175:371–376.PubMedCrossRefGoogle Scholar
  8. 8.
    Knowles DM, Chamuluk GA, Subar M, Dalla-Favera R. (1988). Lymphoid neoplasia associated with acquired immune deficiency syndrome (AIDS): The New York University experience. Ann Intern Med 108: 744–753.PubMedGoogle Scholar
  9. 9.
    Horning SJ, Rosenberg SA. (1984) The natural history of initially untreated low-grade non-Hodgkin’s lymphomas. N Eng J Med 311:1471–1475.CrossRefGoogle Scholar
  10. 10.
    Swerdlow SH. (1992) Post-transplant lymphoproliferative disorders: a morphologic, phenotypic and genotypic spectrum of disease. Histopathol 20:373–385.CrossRefGoogle Scholar
  11. 11.
    Ford RJ, Goodacre A, Ramiriz I, Mehta R, Cabanillas F. (1990). Establishment and characterization of human B cell lymphoma cell lines using B-cell growth factor. Blood 75:1311–1318.PubMedGoogle Scholar
  12. 12.
    Ford RJ, Tamayo A, Ambrus JL (1992) Isolation of autocrine B cell growth factors from effusions of patients with high grade B cell lymphomas. Manuscript submitted for publication.Google Scholar
  13. 13.
    Ambrus JL, Fauci AL, Tamayo A, Li J, Ford RJ. (1992) Cloning of a c-DNA for high molecular weight B cell growth factor (HMW-BCGF). Submitted for publication.Google Scholar
  14. 14.
    Kreitman RJ, Fitzgerald D. Pastan I. (1992) Targeting growth factor receptors with fusion toxins. Int J Immunopharmac 14:465–472.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • R. J. Ford
    • 1
  • A. Tamayo
    • 1
  • J. L. AmbrusJr.
    • 2
  1. 1.University of Tx-MD Anderson Cancer Ctr.HoustonUSA
  2. 2.Washington Univ. Med SchoolSt. LouisUSA

Personalised recommendations