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Adhesion-dependent survival of normal and leukemic human B lymphoblasts on
bone marrow stromal cells
A Manabe, KG Murti, E Coustan-Smith, M Kumagai, FG Behm, SC Raimondi and D Campana
Department of Hematology-Oncology, St Jude Children's Research Hospital,
Memphis, TN 38101.
We investigated the requirement for intimate contact between bone marrow
stroma and B lymphoblasts from normal donors and children with leukemia. By
scanning electron microscopy, both normal and leukemic cells seeded onto
stroma were surrounded by folds of stromal cells or were linked to the
stroma by fine tendrils and uropods. Separation of normal B progenitors
from stroma by use of microporous membranes led to significantly lower cell
recoveries compared with results when contact was unimpeded. For instance,
22.5% +/- 1.8% (mean +/- SEM) of CD19+, CD34+ cells (most immature subset)
were recovered after a 7-day culture directly on stroma, compared with 5.2%
+/- 0.7% after growth on membranes (P < .001 by Student's t test). In 6
of 11 cases of B-lineage acute lymphoblastic leukemia, separation of
progenitors from stroma resulted in apoptosis and a greater than 60%
reduction in cell recovery. In the remaining 5 cases, however, this effect
was much less pronounced, with reductions in cell recoveries ranging from
48.5% to less than 1% (median, 39.0%) of control values. Inhibition of very
late antigen-4, a surface molecule critical for adhesion of B lymphoblasts
to stroma, was associated with a greater loss of normal CD34+ B progenitors
compared with that for equivalent leukemic cells. These results establish
direct contact with stroma as a survival requirement of normal B
lymphoblasts and show marked heterogeneity in stromal dependency among
B-lineage leukemic cells.
Volume 83,
Issue 3,
pp. 758-766,
02/01/1994
Copyright © 1994 by The American Society of Hematology
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