Stimulation of proliferation and differentiation of acute myeloid leukemia cells on a bone marrow stroma in culture.
Purified acute myeloid leukemia (AML) blasts were placed in Dexter cultures with and without a preestablished normal bone marrow stroma to investigate whether their proliferation was dependent on a stroma, as is the case with normal marrow cells. It was also studied whether AML cells were induced to differentiate under a stromal influence. Ten patients with untreated AML were included in the study. In most cases, AML cells were maintained at higher levels when a normal stroma was present. Cell recoveries varied widely between patients. Net cell production was apparent in nine of ten stroma cultures. In most paired cultures without a preestablished stroma, cell numbers decreased. Leukemic colony-forming cells (L-CFU) (clonogenic cells) were also recovered in higher numbers from stroma cultures, but decreased rapidly. The peak of L-CFU preceded that of AML nucleated cells. Cytogenetic analysis (three cases) confirmed the AML karyotype of cultured cells. AML blasts were tested weekly with a number of monoclonal antibodies. During culture, the percentage of cells expressing mature monocytic and granulocytic surface antigens increased markedly, suggesting progressive maturation. Morphologic maturation at the same time was incomplete. Thus, AML cells proliferate and differentiate in vitro under the influence of a normal bone marrow stroma, a property which these cells share with normal bone marrow cells.
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis; D001853:Bone Marrow / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D006098:Granulocytes / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm