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HW Findley , MX Zhou, R Davis, Y Abdul-Rahim, R Hnath and AH Ragab
Division of Pediatric Hematology/Oncology, Emory University, Atlanta, GA
30322.
Recently, low-molecular-weight B-cell growth factor (LMW-BCGF) has been
reported to stimulate growth of leukemic cells from B-cell precursor- acute
lymphoblastic leukemia (BCP-ALL). We further investigated the effects of
LMW-BCGF on proliferation of leukemic clonogenic (progenitor) and
nonclonogenic (progeny) cells from children with BCP- ALL (28 patients) and
B-cell ALL (two patients). Patients were either at diagnosis (n = 18) or in
relapse (n = 12). Response of leukemic progenitor cells was determined by
culturing cells (10(5) cells/mL) in methylcellulose with 0.1 U/mL LMW-BCGF.
Colonies (greater than 20 cells) were counted at day 7. The response of the
leukemic progeny population was determined by DNA synthesis studies using
tritiated- thymidine and by DNA quantitation with propidiumiodide for
determination of cell-cycle status. LMW-BCGF supported growth of leukemic
progenitor cells from 20 of 28 (71%) BCP-ALL and two of two B- cell ALL
patients. Colony numbers ranged from 7 to 2,400 (mean 145, median 45). A
dose-response effect in colony growth was noted, with an apparent plateau
at approximately 2.0 U/mL LMW-BCGF. Colony cells were primarily of leukemic
phenotype (CD19+/CD10+/-). LMW-BCGF also induced significant increases in
leukemic progeny cell proliferation as measured by both thymidine
incorporation (stimulation indexes of 1.6 to 34) and by cell-cycle assay
(percentage S+ G2/M stimulation indexes of 1.6 to 6). LMW-BCGF was more
effective in stimulating leukemic proliferation than three recombinant
interleukins (rIL-2, rIL-3, rIL- 4), although rIL-3 was able to support
colony growth in 4 of 11 patients. These results indicate that LMW-BCGF
and, to a lesser degree rIL-3, are able to stimulate proliferation of
BCP-ALL progenitor and progeny cells, whereas rIL-2 and rIL-4 do not
support progenitor cell proliferation and have only marginal effects on
leukemic progeny cell proliferation.
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