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Prevalence and growth characteristics of malignant stem cells in B- lineage
acute lymphoblastic leukemia
H Nishigaki, C Ito, A Manabe, M Kumagai, E Coustan-Smith, Y Yanishevski, FG Behm, SC Raimondi, CH Pui and D Campana
Department of Hematology-Oncology, St Jude Children's Research Hospital,
University of Tennessee College of Medicine, Memphis 38105, USA.
We used a stroma-supported culture method to study the prevalence and
growth characteristics of malignant stem cells in acute lymphoblastic
leukemia (ALL). In 51 of 108 B-lineage ALL samples, bone marrow-derived
stroma not only inhibited apoptosis of ALL cells but also supported their
proliferation in serum-free medium. When single leukemic cells were placed
in the stroma-coated wells of microtiter plates, the percentage of wells
with leukemic cell growth after 2 to 5 months of culture ranged from 6% to
20% (median, 15%; 5 experiments). The immunophenotypes and genetic features
of cells recovered from these cultures were identical to those noted before
culture. All cells maintained their stroma dependency and self-renewal
capacity. Leukemic clones derived from single cells contained approximately
10(3) to 10(6) cells after 1 month of culture; other clones became
detectable only after prolonged culture. Cell growth in stroma-coated wells
correlated with the number of initially seeded cells (1 or 10; r = .87).
However, the observed percentages of positive wells seeded with 10 cells
always exceeded values predicted from results with single-cell-initiated
cultures (P < .003 by paired t-test), suggesting stimulation of leukemic
cell growth by paracrine factors. In conclusion, the proportion of ALL
cells with clonogenic potential may be considerably higher than previously
thought.
Volume 89,
Issue 10,
pp. 3735-3744,
05/15/1997
Copyright © 1997 by The American Society of Hematology

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