Chimaeric cultures of human marrow stroma and murine leukaemia cells: evidence for abnormalities in the haemopoietic microenvironment in myeloid malignancies and other infiltrating marrow disorders.
PGM-1 is a transplantable C3H/HeJ leukaemia which is not viable in unstimulated in vitro culture, differentiates into mature granulocytes and macrophages in response to soluble cytokines, and undergoes self-renewing cell divisions in coculture with selected human bone marrow stromal cell lines. When PGM-1 cells were cultured on pre-established adherent layers from primary human marrow samples, their fate depended on the source of the human marrow. Adherent layers from healthy marrow donors or patients with reactive marrow alterations had no or very little capacity to maintain PGM-1 cells in an immature colony-forming state. However, in coculture with adherent layers from patients with myeloid leukaemia or, to a lesser extent, lymphoblastic leukaemia or marrow-infiltrating lymphoma the colony-forming potential was retained. There was no correlation between the remission status of the patient and the PGM-1 activity of the adherent layer. Consistent morphological differences between active and inactive stromal layers were not observed. The PGM-1 coculture system enables the detection of a hitherto undescribed regulatory abnormality in bone marrow malignancies. Whether the PGM-1 supporting activity is mediated through differences in the production of a cytokine with close homology to complement factor Bb which has recently been shown to induce self-renewal in immature PGM-1 cells, requires further investigation.
Dührsen
U
U
Abteilung für Onkologie und Hämatologie, Medizinische Klinik, Universitätskrankenhaus Eppendorf, Hamburg, Germany.
Knieling
G
G
Beecken
W
W
Neumann
S
S
Hossfeld
D K
DK
D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D002470:Cell Survival; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology; D017154:Stromal Cells / Q000473:pathology*; D013997:Time Factors; D014407:Tumor Cells, Cultured