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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