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Long-term leukemia-initiating capacity of a CD34-subpopulation of acute
myeloid leukemia
W Terpstra, A Prins, RE Ploemacher, BW Wognum, G Wagemaker, B Lowenberg and JJ Wielenga
Institute of Hematology, Erasmus University, Rotterdam, The Netherlands.
Acute myeloid leukemia (AML) proliferation in vivo is maintained by a small
fraction of progenitor cells. These cells have been assumed to express an
immature phenotype and to produce most colony-forming units (CFU-AML). For
one case of AML (French-American-British [FAB] M1, normal cytogenetics), we
examined the capacity of the CD34+ (25% of unseparated AML cells) and CD34-
fractions to initiate leukemia in severe combined immunodeficient (SCID)
mice. In addition, the production of CFU-AML and nucleated cells (NC) of
these subsets was investigated in long-term bone marrow culture (LTBMC).
The frequencies of cobblestone area-forming cells (CAFC) were also
estimated; early appearing cobblestone areas (CAs) are indicative of
relatively mature progenitors and late CAs represent the progeny of
primitive progenitors. In mice transplanted with CD34- (98% pure) or CD34+
(98% pure) grafts, similar AML cell growth was seen throughout an
observation period of 106 days. The capacity to establish long-term growth
from the CD34- cells was confirmed by renewed outgrowth after
retransplantation. In vitro, the CD34- fraction contained both immature and
mature CAFCs and produced high numbers of CFU-AML and NC in LTBMC. The
CD34+ fraction produced only small numbers of CFU-AML, NC, and mature
CAFCs. Therefore, the expression of CD34 and the content of CFU- AML were
not associated with long-term growth of AML. However, similar frequencies
of primitive CAFCs were observed in both fractions. Thus, both CD34- and
CD34+ subsets of this AML sample contained immature progenitors with the
capacity to initiate long-term AML growth as characterized in vivo (in SCID
mice) as well as in vitro (in CAFC assay), indicating asynchrony between
functional and immunophenotypical maturation of AML progenitor cell
compartments.
Volume 87,
Issue 6,
pp. 2187-2194,
03/15/1996
Copyright © 1996 by The American Society of Hematology
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