N. Sawai et al., ABERRANT GROWTH OF GRANULOCYTE-MACROPHAGE PROGENITORS IN JUVENILE CHRONIC MYELOGENOUS LEUKEMIA IN SERUM-FREE CULTURE, Experimental hematology, 24(2), 1996, pp. 116-122
We investigated the properties of granulocyte-macrophage (GM) progenit
ors obtained from patients with juvenile chronic myelogenous leukemia
(JCML). CD34(+) bone marrow cells from a patient with JCML, unlike nor
mal bone marrow cells, generated a large number of cells in serum-cont
aining liquid culture without additional hematopoietic factors. In ser
um-deprived culture, only granulocyte colony-stimulating factor (G-CSF
) had a modest stimulatory effect on GM colony growth in normal contro
ls. In contrast, stem cell factor (SCF), granulocyte-macrophage colony
-stimulating factor (GM-CSF), and interleukin-3 (IL-3), as well as G-C
SF, when tested individually, generated significant numbers of GM colo
nies in some JCML patients. All two-factor combinations generated sign
ificantly more GM colonies in JCML compared with normal controls. In p
articular, GM-CSF plus SCF exerted an interaction equivalent to the al
l-factor combination in most patients. Significant differences in the
size and constituent cells of GM colonies stimulated by GM-CSF plus SC
F were also observed. These results suggest that one possible mechanis
m for the excessive cell production in JCML is the strong proliferatio
n of GM progenitors induced by hematopoietic factors, especially SCF.
According to immunofluorescent analysis, however, it is unlikely that
this multiplication is due to an increase in the cell surface expressi
on of c-kit receptors on JCML progenitors.