B-cell chronic lymphocytic leukaemia cells express and release transforming growth factor-beta.
Transforming growth factor-beta (TGF-beta) has been described as a potent inhibitor of various cell types, among others of primitive haematopoietic progenitors in vitro, and as a negative autocrine regulator of normal B lymphocyte growth and differentiation. In the present study we investigated TGF-beta gene expression in peripheral blood mononuclear cells (PBMC) and in B cells from patients with B-cell chronic lymphocytic leukaemia (B-CLL) and from normal controls. Monocyte depleted B-CLL cells expressed constitutively mRNA for TGF-beta 1 and secreted low amounts of TGF-beta activity into the culture medium. Stimulation of cells by phorbol ester noticeably enhanced mRNA levels as well as protein secretion in most cases. TGF-beta activity was of the same magnitude as in normal controls. We next analysed TGF-beta in highly enriched B lymphocytes from B-CLL (95-100% CD19+), and found that TGF-beta secretion was up to 3 times higher than in the original PBMC population. It is discussed that B-CLL cells might escape from negative regulation by TGF-beta and, on the other hand, inhibit normal haematopoietic cell proliferation and thereby achieve a growth advantage in the haematopoietic tissues.
Kremer
J P
JP
GSF-Institut für Experimentelle Hämatologie, München, Germany.
Reisbach
G
G
Nerl
C
C
Dörmer
P
P
D000368:Aged; D000369:Aged, 80 and over; D001681:Biological Assay; D015152:Blotting, Northern; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000235:genetics
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta