Stepwise progression of B cell malignancy occurred in a bone marrow stromal cell-dependent pre-B cell clone.
The murine long-term bone marrow culture system which can support the almost infinite growth of normal B lineage cells was used to establish the experimental model for spontaneous B cell leukemogenesis. At the early phase of the culture, B cell differentiation with diversification of immunoglobulin genes was induced. However, the culture was finally captured by a single B cell clone which had the fastest growth rate. The B cell clone was strictly dependent on stromal cells for in vitro growth and did not generate leukemia when injected into syngenic mice. After up to a year of maintenance of the clone, the leukemic cells developed spontaneously. The leukemic cell line isolated in vivo retained the stromal cell-dependency, and further in vitro selection process was required to establish the stromal cell-independent leukemic cell line. These leukemic cell lines highly expressed c-myc and Ha-ras genes regardless of stromal cell-dependency. We detected no chromosomal aberrations accompanied with the process of leukemic transformation. Our results suggest that spontaneous neoplastic transformation of B cells in long-term bone marrow culture occurs in a stepwise manner.
Ogawa
M
M
Institute for Medical Immunology, Kumamoto University Medical School, Japan.
Ikuta
K
K
Katsura
Y
Y
Nishikawa
S
S
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D002999:Clone Cells; D007621:Karyotyping; D015448:Leukemia, B-Cell / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011519:Proto-Oncogenes; D014407:Tumor Cells, Cultured