13
RECEPTORS FOR CYTOKINE AND GROWTH
FACTORS ON B-CLL LYMPHOCYTES
 
DP COLLINS
 
    Cytokines are a diverse group of peptide proteins which play a key role in directing the growth, development, and differentiation of the hematopoietic and immune systems. Cytokines have also been demonstrated to have growth factor activity on isolated leukemia cells and are potentially involved in the development, growth and survival of leukemia cells in vivo. Cellular responses to cytokines are mediated by specific receptors on the cell surface.
 
    The role of cytokines and cytokine receptors in the development of leukemia suggests their suitability as a potential target of immuno—and chemotherapeutic modalities. Additionally, the presence or absence of specific cytokine receptors on the surface of cells could be used as an additional phenotyping tool in conjunction with other surface receptor antibodies to differentiate leukemia cells from normal cells by flow cytometric analysis of peripheral blood cells.
 
    Biotinylated and fluorochrome-labeled cytokines were used in preliminary studies to detect and compare the presence of cytokine receptors on the surface of several types of B-cell populations (See Table 1).
 
    Our data suggest the presence of several cytokine receptors that distinguish HCL and CLL cells from normal resting or activated B-cells (Table 1). In addition, both leukemic cells and activated normal B-cells showed increased fluorescence intensity, probably reflecting elevated receptor expression, for Interleukins -2, -4, and -6, and for TNF-alpha.
 
    Traditionally, cell surface immunoglobulin light chain (kappa or lambda) clonality is the criteria for flow cytometric analysis of CLL. In instances of minimal residual disease or in the early stages or clonal emergence, light chain clonal analysis may not be sensitive enough to detect monoclonal populations.  The use of specific cytokine receptors as an additional analysis tool could aid in early or residual detection. The presence of any of the receptors in Table 1 on CD19-positive cells strongly suggests an abnormal B-cell population.  These assays could be used in conjunction with kappa-lambda analysis as a screening tool in surveys of B-cell lymphoproliferative disorders.
 
 
 
 
 
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