The importance of Notch signaling in peripheral T-cell lymphomas

TY - JOUR

T1 - The importance of Notch signaling in peripheral T-cell lymphomas

AU - Kamstrup, Maria Rørbæk

AU - Biskup, Edyta

AU - Gjerdrum, Lise Mette Rahbek

AU - Ralfkiaer, Elizabeth

AU - Niazi, Omid

AU - Gniadecki, Robert

PY - 2014/3

Y1 - 2014/3

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 - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Amyloid Precursor Protein Secretases

KW - Apoptosis

KW - Cell Cycle Checkpoints

KW - Cell Line, Tumor

KW - Child

KW - Child, Preschool

KW - Female

KW - Humans

KW - Lymphoma, T-Cell, Peripheral

KW - Male

KW - Middle Aged

KW - Oligopeptides

KW - Receptor, Notch1

KW - Receptors, Notch

KW - Signal Transduction

KW - Young Adult

U2 - 10.3109/10428194.2013.807510

DO - 10.3109/10428194.2013.807510

M3 - Journal article

C2 - 23697875

SN - 1042-8194

VL - 55

SP - 639

EP - 644

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

IS - 3

ER -