Differential regulation of Notch signal transduction in leukaemia and lymphoma cells in culture.
The transduction of Notch signal plays an intricate role in cell differentiation and pathogenesis of haematological malignancies as well as in certain congenital conditions. We found no genomic changes in either gene in 34 leukaemic samples and 25 leukaemia and lymphoma cell lines. The functionality of Notch signalling was tested using HES1 gene activation. We show that Notch signalling is differentially regulated in T-acute lymphoblastic leukaemia (ALL) and B-lymphoma cells. The Notch pathway is intact in a majority of B-lymphoma cell lines, but EBNA2, which mimics notch function, can occasionally activate the pathway. In contrast, the Notch pathway is constitutively active in T-ALL. This is the first demonstration of a distinction between B-lymphomas and T-cell leukaemias in the functioning of the Notch-signalling pathway. This might be related to their pathogenesis.
Chiaramonte
Raffaella
R
Department of Biomedical Sciences and Technologies, University of Milano, LITA-via Fratelli Cervi 93-20090 Segrate (MI), Italy.
Calzavara
Elisabetta
E
Balordi
Francesca
F
Sabbadini
Marta
M
Capello
Daniela
D
Gaidano
Gianluca
G
Serra
Anna
A
Comi
Paola
P
Sherbet
G V
GV
D045744:Cell Line, Tumor; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D014764:Viral Proteins
C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D014157:Transcription Factors; D014764:Viral Proteins