TY - JOUR
T1 - The importance of Notch signaling in peripheral T-cell lymphomas
AU - Kamstrup, Maria Rorbæk
AU - Biskup, Edyta
AU - Gjerdrum, Lise Mette Rahbek
AU - Ralfkiaer, Elizabeth
AU - Niazi, Omid
AU - Gniadecki, Robert
PY - 2014/3/1
Y1 - 2014/3/1
N2 - Peripheral T-cell lymphomas (PTLs) represent an area of high medical need. Previously, we demonstrated high expression of Notch, a known oncogene, in primary cutaneous anaplastic large cell lymphoma (ALCL). In this study, we performed immunohistochemical staining for Notch1 in lymph nodes from PTL not otherwise specifi ed (PTL-NOS) and systemic ALCL (ALK + and ALK - ) and report a similar distribution among the three subgroups: Negative, moderate and strong expression was, respectively, 18%, 27% and 55% for PTL-NOS (33 cases), 20%, 0% and 80% for ALCL ALK - (10 cases) and 45%, 22% and 33% for ALCL ALK - (nine cases) ( p <0.05). In the ALK - ALCL cell line, Karpas-299, pharmacological inhibition of Notch with γ -secretase inhibitor (GSI) I was far more potent than with GSI IX, XX and XXI with regard to cell viability and apoptosis. In conclusion, PTL tumor cells have prominent Notch1 expression and treatment with Notch inhibitors has cytotoxic eff ects
AB - Peripheral T-cell lymphomas (PTLs) represent an area of high medical need. Previously, we demonstrated high expression of Notch, a known oncogene, in primary cutaneous anaplastic large cell lymphoma (ALCL). In this study, we performed immunohistochemical staining for Notch1 in lymph nodes from PTL not otherwise specifi ed (PTL-NOS) and systemic ALCL (ALK + and ALK - ) and report a similar distribution among the three subgroups: Negative, moderate and strong expression was, respectively, 18%, 27% and 55% for PTL-NOS (33 cases), 20%, 0% and 80% for ALCL ALK - (10 cases) and 45%, 22% and 33% for ALCL ALK - (nine cases) ( p <0.05). In the ALK - ALCL cell line, Karpas-299, pharmacological inhibition of Notch with γ -secretase inhibitor (GSI) I was far more potent than with GSI IX, XX and XXI with regard to cell viability and apoptosis. In conclusion, PTL tumor cells have prominent Notch1 expression and treatment with Notch inhibitors has cytotoxic eff ects
KW - γ-secretase inhibitors
KW - Notch
KW - Peripheral T-cell lymphoma not otherwise specified
KW - Systemic anaplastic large cell lymphoma
UR - http://www.scopus.com/inward/record.url?scp=84894426454&partnerID=8YFLogxK
U2 - 10.3109/10428194.2013.807510
DO - 10.3109/10428194.2013.807510
M3 - Article
C2 - 23697875
AN - SCOPUS:84894426454
SN - 1042-8194
VL - 55
SP - 639
EP - 644
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 3
ER -