Differences of cellular composition and adhesion molecule expression in "leukemic" as compared with "normal" human long-term bone marrow cultures.
Human long-term bone marrow cultures (HLTBMCs) were established with bone marrow samples collected from 15 patients with acute myeloid leukemia (AML) and compared with HLTBMCs from eight healthy volunteers. During 6 weeks of culture, the cellular composition of HLTBMCs was quantitatively studied. The cells of the HLTBMCs were divided into three main categories: fibroblasts, macrophages, and 'other cells' (endothelial cells, hematopoietic cells and undefined cells). HLTBMCs derived from healthy volunteers demonstrated a very consistent development. The number of fibroblasts increased during culture and the number of macrophages decreased, resulting in a steady state after 3 weeks of culture. In contrast, HLTBMCs derived from patients with AML showed a strikingly different pattern of irregular development and a steady state was not reached under our conditions. The APAAP technique was used to demonstrate expression of adhesion molecules. VLA2, VLA5, VLA6, LFA1, Mac1, p150/95, beta 2-chain, HCAM, ICAM1, NCAM, and VCAM1 were more expressed on 'normal' as compared with 'leukemic' bone marrow stromal cells, although this reached significance only for beta 2-chain and NCAM. VLA1, 3, and 4 were expressed in a higher percentage on 'leukemic' stroma (not significant). More expression was seen on 'normal' as opposed to 'leukemic' macrophages for the adhesion molecules tested, except for VLA5. The differences reached significance for the majority of molecules tested. It is concluded that striking differences exist in cellular composition and adhesion molecule expression between HLTBMCs from healthy individuals and those from patients with AML. This may have an impact on the pathogenesis of AML.
Denkers
I A
IA
Department of Hematology, Free University, Amsterdam, The Netherlands.
Beelen
R H
RH
Ossenkoppele
G J
GJ
de Jong-de Boer
A J
AJ
Langenhuijsen
M M
MM
D000208:Acute Disease; D000469:Alkaline Phosphatase / Q000032:analysis; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis*; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology* / Q000502:physiology; D001854:Bone Marrow Cells; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000473:pathology* / Q000502:physiology; D007951:Leukemia, Myeloid / Q000473:pathology*; D008264:Macrophages / Q000166:cytology / Q000473:pathology; D012016:Reference Values
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D000469:Alkaline Phosphatase