Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Notch-signalling has been implicated as a pathogenetic factor and a therapeutical target in T-cell leukaemias and in some lymphomas of B-cell origin. Our aim was to investigate the role of Notch-signalling in apoptosis regulation in human non-Hodgkin B-cell lymphoma (B-NHL) cell lines and in primary chronic lymhocytic leukaemia (CLL) cells using Delta-like 4 (Dll4) ligand mediated Notch activation and gamma-secretase inhibitor (GSI) mediated Notch inhibition in vitro. The potential cross-talk of Notch with the transforming growth factor-beta (TGFb) pathway in apoptosis induction was also explored, and the effect of GSI on drug-induced apoptosis was assessed. Modulation of Notch-signalling by itself did not change the rate of apoptosis in B-NHL cell lines and in CLL cells. TGFb-induced apoptosis was decreased - but not completely abolished - by GSI in TGFb-sensitive cell lines, but resistance to the apoptotic effects of TGFb were not reversed by Notch activation or inhibition. Drug-induced apoptosis was not modified by GSI. We identified Hairy/Enhancer of Split (HES)-1 as a TGFb target gene in selected - TGFb-sensitive - B-NHL cell lines. TGFb-induced HES-1 was only partially Notch-dependent in later phases. Apoptosis regulation by TGFb and GSI was not dependent on the transcriptional regulation of c-myc. In conclusion, our data does not support a unifying role of Notch in regulating apoptosis in B-NHL, but warns that gamma-secretase inhibitors may actually counteract apoptosis in some cases.
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PMID:Notch-regulation upon Dll4-stimulation of TGFb-induced apoptosis and gene expression in human B-cell non-Hodgkin lymphomas. 2001 7

Posttransplantation non-Hodgkin lymphoma is a life-threatening complication after transplantation. Although pharmacologically suppressed adaptive immunity plays a major role in its development, the role of innate immunity in posttransplantation lymphoma is unknown. We assessed the 158 V/F polymorphism in the Fc-gamma receptor 3A gene (FCGR3A), killer cell immunoglobulin-like receptor (KIR) genotype, KIR ligand status, and a single nucleotide polymorphism affecting the production of interferon-gamma (IFN-gamma; +874 A/T) in 236 patients with posttransplantation lymphoma reported to the Collaborative Transplant Study. In addition, polymorphisms in the interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) genes previously associated with lymphoma development were also typed. Using a split-cohort approach, gene/allele frequency was related to the 5-year patient survival after the diagnosis of lymphoma and compared with 100 control solid organ transplant recipients. FCGR3A and KIR genotype significantly influenced survival after diagnosis of posttransplantation lymphoma: the hazard of dying was reduced in homozygous carriers of the high-affinity V allele (hazard ratio 0.49, 95% confidence interval 0.29-0.82, P = .006), whereas carrying a genotype including KIR2DL2/KIR2DS2 increased the risk of dying (hazard ratio 1.49, 95% confidence interval 1.07-2.05, P = .02). KIR ligands and cytokine polymorphisms had no effect on survival. None of the genetic loci analyzed emerged as risk factors for lymphoma development.
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PMID:Natural killer-cell receptor polymorphisms and posttransplantation non-Hodgkin lymphoma. 2020 82


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