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Association between clonogenic cell growth and clinical risk group in B-
cell chronic lymphocytic leukemia
R Dadmarz, SN Rabinowe, SA Cannistra, JW Andersen, AS Freedman and LM Nadler
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA
02115.
Chronic lymphocytic leukemia of B-cell origin (B-CLL) is a disease with a
variable clinical course, despite the fact that the neoplastic cells in
this disorder are homogeneous with respect to morphology, immunophenotype,
and cell cycle stage. To further investigate the heterogeneity observed in
the clinical behavior of B-CLL, we determined the phenotype and growth
requirements of clonogenic cells from 28 patients with B-CLL from low-,
intermediate-, and high-risk groups as defined by the Rai staging system.
Using methyl-cellulose as a semi- solid media with feeder cells and/or
growth factors, colonies were observed with one or more of the culture
conditions tested in 25 of 28 CLLs. Phenotypic analysis of colonies
demonstrated that the clonogenic cells uniformly expressed la, CD19, CD20,
CD5, and the identical light chain as the original CLL cell cultured.
However, heterogeneity was observed in clonogenic B-CLL cell growth among
the three different CLL risk groups. Clonogenic cells from patients with
low-risk CLL required either irradiated unstimulated T cells, with or
without conditioned media (CM) or irradiated activated T cells alone for
colony formation. Both the number of colonies (227 +/- 15) as well as the
number of cells per colony (220 +/- 82) were large, with a mean cloning
efficiency of 0.39%. In contrast, clonogenic cells from patients with
intermediate- and high-risk CLL required the combination of both irradiated
activated T cells and CM. As compared with the low-risk CLLs, both the
number and size of the colonies formed by the intermediate- (74 +/- 17, 70
+/- 39) and high- (83 +/- 28, 40 +/- 14) risk groups were significantly
lower (P less than .0001). Similarly, the mean cloning efficiency was
significantly reduced to 0.15% and 0.14%, respectively. None of the
recombinant cytokines (interleukin 1 [IL-1] to IL-7, tumor necrosis factor,
alpha and gamma-interferon, B-cell growth factor, and granulocyte
macrophage colony-stimulating factor) alone or in combination with each
other could entirely replace the stimulatory effect of the activated T
cells. These data suggest that clinical progression of B-CLL is associated
with a loss of clonogenic potential in the circulating pool of neoplastic
cells, which require as yet undefined factors provided by activated T cells
and CM.
Volume 76,
Issue 1,
pp. 142-149,
07/01/1990
Copyright © 1990 by The American Society of Hematology
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