TGF-beta and its receptor complex in leukemic B-cell precursors.
Transforming growth factor beta (TGF-beta) is a highly conserved peptide with growth-inhibitory activity in multiple normal and transformed cell types. Signal transduction is mediated through the receptor complex, consisting of two active seronine or threonine kinases (TGF-beta-receptor I and II) and the receptor-associated proteins betaglycan (TGF-beta-receptor III) and endoglin. In this study, we assessed the analysis of the role of TGF-beta and the transcription of the genes for TGF-beta and its receptor in highly purified leukemic B-cell precursors (BCPs) of patients with common acute lymphoblastic leukemia (cALL). Leukemic BCPs were positive for gene transcription of TGF-beta (9/9), the TGF-beta-receptor I (9/9), the TGF-beta-receptor II (6/6), betaglycan (5/6), and endoglin (6/6). Incubation with TGF-beta significantly reduced the cell viability of leukemic BCPs by a mean of 45% (p = 0.0009). The reduction of cell viability was associated with the induction of apoptosis by a mean of 31%. TGF-beta caused significant suppression of the S phase (p = 0.002) and accumulation in the G0/G1 phase (p = 0.0005). It also reduced expression of the adhesion surface receptor CD18 and the Fas antigen CD95 from 58% to 40% and from 48% to 27%, respectively. The data indicate that TGF-beta is a negative growth signal in leukemic BCPs and point to an additional role of TGF-beta as an immunomodulatory cytokine, suggesting a complex role of TGF-beta in the leukemogenesis of cALL.
Buske
C
C
Department of Hematology and Oncology, University of Göttingen, Germany.
Becker
D
D
Feuring-Buske
M
M
Hannig
H
H
Griesinger
F
F
Hiddemann
W
W
Wörmann
B
B
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000503:physiopathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000503:physiopathology; D012313:RNA / Q000032:analysis; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D012313:RNA