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Primitive human hematopoietic precursors express Bcl-x but not Bcl-2
JR Park, ID Bernstein and DM Hockenbery
Molecular Medicine Programs, Fred Hutchinson Cancer Research Center,
Seattle, WA 98109, USA.
Bcl-2 and its homologue, bcl-xL, encode membrane-associated proteins that
suppress programmed cell death of hematopoietic cell lines after growth
factor withdrawal, and are expressed in hematopoietic precursor cells. To
better understand the maintenance of long-term survival in the
hematopoietic stem cell population, we evaluated the expression patterns of
Bcl-2 and Bcl-x in primitive hematopoietic precursor populations.
Hematopoietic precursor cells expressing CD34 (CD34+) and lacking
maturation-linked surface antigens (lin-) were isolated from adult human
bone marrow using two-color immunofluorescence cell sorting and
fractionated on the basis of forward light scatter characteristics into
blast-sized and small to medium lymphocyte-sized cell populations. Bcl-2
expression was shown in 78% to 90% of CD34+ lin- blast-sized cells versus
less than 10% of small to medium lymphocyte-sized CD34+ lin- cells by
immunohistochemical analysis. Small to medium lymphocyte- sized CD34+ lin-
cells were further enriched for primitive precursors by selecting cells
that lacked expression of CD38 (CD34+ lin- CD38-). In parallel experiments,
only 1% to 4% of CD34+ lin- CD38- cells expressed Bcl-2, whereas 45% to 56%
of these cells generated colony- forming cells. In contrast, > or = 94%
of cells in all bone marrow subpopulations studied expressed Bcl-x protein.
Both alternatively spliced bcl-x transcripts, bcl-xL and bcl-xs, were
present. Our data show that the most primitive hematopoietic precursors
express Bcl-x but not Bcl-2. Thus, the functional bcl-2 homologue, bcl-xL,
may be essential for the long-term survival of the hematopoietic stem cell
population.
Volume 86,
Issue 3,
pp. 868-876,
08/01/1995
Copyright © 1995 by The American Society of Hematology
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