Cell culture studies and oncogene expression in juvenile chronic myelogenous leukemia.
Juvenile chronic myelogenous leukemia (JCML) may be distinguished from adult CML based upon in vitro cell growth characteristics. We studied four untreated children with JCML and report additional unique findings. Peripheral blood (PB) and bone marrow (BM) cells were grown in soft agar. Without exogenous colony-stimulating activity (CSA) there was exuberant "spontaneous" colony formation in both PB and BM cultures. In the absence of exogenous stimulus, PB colony morphology was predominantly, but not exclusively, monocyte/macrophage. When PB was depleted of adherent cells, "spontaneous" colony formation was nearly completely abrogated. Cultures were also performed in the presence of various sources of CSA including giant cell tumor-conditioned medium (GCT-CM), a melanoma cell line-CM (LD1-CM), human placenta-CM (HPCM), and normal PB mononuclear cell (PBMC) feeder layers. Colony formation was typically increased with HPCM and PBMC, whereas in two patients GCT-CM and LD1-CM failed to stimulate additional colony growth when compared to cultures without exogenous CSA and, in fact, appeared to inhibit baseline "spontaneous" growth. The morphology of colonies in the presence of exogenous stimuli was highly variable. Because of the recent association between the c-fms protooncogene product and the receptor for the monocyte growth factor CSF-1, we analyzed the PB cells from two JCML patients for c-fms expression. Although expressed, c-fms levels were less than that in an adult with Ph1-positive CML in chronic phase. These studies indicate that in JCML, there are dramatic increases in both PB and BM colony-forming cells and that "spontaneous" growth is dependent on an accessory adherent cell fraction. Furthermore, patterns of responsiveness to various sources of CSA suggest that the colony-forming cells may not be a uniform population of malignant cells.
Gualtieri
R J
RJ
Department of Medicine, Children's Hospital of Alabama, University of Alabama, Birmingham 35294.
Castleberry
R P
RP
Gibbons
J
J
Miller
D M
DM
Berkow
R L
RL
Parmley
R T
RT
Banks
J
J
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002675:Child, Preschool; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D003470:Culture Media / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology*; D008264:Macrophages; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009000:Monocytes; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016186:Receptor, Macrophage Colony-Stimulating Factor; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014410:Tumor Stem Cell Assay
D003115:Colony-Stimulating Factors; D003470:Culture Media; D011518:Proto-Oncogene Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor