Bw. Long et al., APOPTOSIS AND INTERLEUKIN-7 GENE-EXPRESSION IN CHRONIC B-LYMPHOCYTIC LEUKEMIA-CELLS, Proceedings of the National Academy of Sciences of the United Statesof America, 92(5), 1995, pp. 1416-1420
mRNA for interleukin 7 (IL-7) was readily detected in leukemic cells i
mmediately upon their removal from patients with chronic B-lymphocytic
leukemia (B-CLL), IL-7 mRNA expression and IL-7 gene transcription we
re down regulated, however, when B-CLL cells were placed in culture at
37 degrees C for 4 hr, Down regulation of the IL-7 gene was prevented
in cells maintained at 4 degrees C, Continued culture of B-CLL cells
at 37 degrees C resulted in programmed cell death, or apoptosis, as ev
idenced by DNA fragmentation, The coincident kinetics of IL-7 gene dow
n regulation and apoptosis suggested that IL-7 gene expression may be
required for maintenance of CLL viability in vivo, Signals for IL-7 ge
ne regulation and apoptosis induction were thus examined, Activation o
f normal B cells through their immunoglobulin receptors did not result
in upregulation of IL-7 gene expression, Reagents required for CLL ce
ll purification and culture also did not contribute to IL-7 gene regul
ation and apoptosis induction, IL-7 gene expression was retained and a
poptosis was prevented, hen-ever, in CLL cells cultured on a monolayer
of EA.hy926 human umbilical cord endothelial hybrid cells, Signals sp
ecifically presented by EA.hy926 cells supported both CLL cell viabili
ty and IL-7 gene expression, whereas culture of CLL cells on A549/8 ca
rcinoma cells, the fusion partner used to generate the EA.hy926 cells,
did not, Cell-cell contact was required, as culture supernatants did
not prevent apoptosis, Specifically, IL-7 mRNA expression was retained
and apoptosis was prevented only by contact with the endothelial cell
hybrids, Preliminary data indicated that integrins expressed on CLL c
ells effected modulation of apoptosis and IL-7 gene regulation, sugges
ting that integrins may play significant roles in regulating viability
of CLL cells.