Proliferation of precursor B-lineage acute lymphoblastic leukaemia by activating the CD40 antigen.
No reliable culture system exists for B-lineage acute lymphoblastic leukaemia (ALL). Recently we found that many different mature B-cell malignancies proliferate upon stimulation via the CD40 antigen, and this led us to investigate whether a similar CD40 activation on ALL cells could also induce proliferation. First, we measured CD40 expression in 21 ALL cases; all were CD40+, although mostly weak. Next, we triggered the CD40 antigen by anti-CD40 antibodies and by a CD40 ligand-expressing cell line. In addition, we measured the influence of IL-3, IL-4 and IL-7 with and without these stimuli. In 8/10 cases proliferation, measured by 3H-thymidine incorporation, could be induced after CD40 crosslinking, especially in the presence of IL-3. Stimulation via the CD40 ligand was more successful than using crosslinked anti-CD40 antibodies. IL-4 inhibited the spontaneous proliferation found in three cases, but stimulated proliferation after CD40 crosslinking. IL-7 did not contribute to proliferation. Morphology, immunophenotyping and surface marker analysis, combined with DNA flow cytometry confirmed that the proliferation found could be ascribed to the ALL cells. In conclusion, B-lineage ALL cases are CD40+, and many can be cultured using CD40 stimulation and IL-3.
Department of Haematology, University Medical Centre, Leiden, The Netherlands.
E V
EV
Planken
N H
NH
Dijkstra
M
M
Bakkus
R
R
Willemze
J C
JC
Kluin-Nelemans
D002051:Burkitt Lymphoma / Q000473:pathology*; D019013:CD40 Antigens / Q000502:physiology*; D002455:Cell Division; D002470:Cell Survival; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015851:Interleukin-7 / Q000502:physiology; D011289:Preleukemia / Q000473:pathology*; D014407:Tumor Cells, Cultured
D019013:CD40 Antigens; D007377:Interleukin-3; D015851:Interleukin-7; D015847:Interleukin-4