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Aberrant responses of human lymphocytic neoplasms to cytokine regulation

Authors
  • Nowell, Peter C.1
  • Moore, Jonni S.1
  • 1 University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, Philadelphia, PA, 19104-6082 , Philadelphia
Type
Published Article
Journal
Immunologic Research
Publisher
Humana Press
Publication Date
Jan 01, 1998
Volume
17
Issue
1-2
Pages
171–177
Identifiers
DOI: 10.1007/BF02786442
Source
Springer Nature
Keywords
License
Yellow

Abstract

Studies in this laboratory have recently focused on two hemic neoplasms: B cell chronic lymphocytic leukemia (B-CLL) and a T cell disorder, Sézary syndrome. These tumors do not have consistent cytogenetic or molecular genetic alterations, and so we have concentrated on their response to and production of various regulatory cytokines. Although B-CLL cells show variable proliferative responses when exposed to transforming growth factor beta (TGFΒ), these cells have consistently shown resistance to the proapoptotic effects of this cytokine. Also, interleukin 4 (IL4), IL5, and interferon-gamma (IFNγ) all show a consistently increased protective effect against apoptosis in B-CLL cells as compared to normal human B cells. Thus, a defect in apoptosis appears to be an important factor in the pathogenesis of CLL. By contrast, the neoplastic T cells of Sézary syndrome show a consistent resistance to the antiproliferative effects of TGFΒ, suggesting that aberrant proliferation is more important than apoptosis in this disorder. In both neoplasms, we have shown that the defective responses to cytokines are in some instances related to alterations in receptor expression, but this has not been true in all circumstances, and other stages in the signaling pathways are being investigated. As we define more precisely the specific defects that contribute to the clonal expansion of these neoplasms, the findings may ultimately lead to improved clinical control of these disorders.

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