Molecular Mechanisms in Non-Hodgkin Lymphoma

2016 ◽  
pp. 561-587
Author(s):  
John Hunt ◽  
Yuri Fedoriw ◽  
William N. Rezuke
Keyword(s):  
Hodgkin Lymphoma ◽  
Molecular Mechanisms ◽  
Non Hodgkin Lymphoma

MCL-1 Critically Regulates Survival Of T-Lymphocyte Non-Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4246-4246
Author(s):  
Sabine Spinner ◽  
Kelly Gemma ◽  
Marco Herold ◽  
Konstanze Pechloff ◽  
Giuliano Crispatzu ◽  
...  
Keyword(s):  
Cell Death ◽  
Hodgkin Lymphoma ◽  
T Lymphocyte ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Whole Body ◽  
Resistance To Therapy ◽  
Non Hodgkin Lymphoma ◽  
Allelic Deletion

Abstract The heterogeneous subgroup of T-lymphocyte non-Hodgkin lymphoma (T-NHL) exhibits an aggressive growth pattern and is relatively insensitive to chemotherapy. The molecular mechanisms of survival and resistance to therapy remain largely undefined. We hypothesized that BCL-2 proteins with anti-apoptotic properties protect T-NHL cells from cell death, cause resistance to therapy and therefore represent an attractive target for therapy. MCL-1 potently protects physiologically healthy T-lymphocytes from cell death, but its function in transformed T-cells is incompletely understood. We therefore dissected the role of MCL-1 using in silico meta-analyses on available gene expression data on human primary T-NHL samples. We identified MCL-1 as the primary BCL-2 family protein to be highly expressed across most major T-NHL subsets. Expression of MCL-1 was restricted to its anti-apoptotic full-length splice variant as opposed to its pro-apoptotic short isoform. To functionally characterize the requirement for MCL-1, we utilized a T-NHL mouse model, which is based on four consecutive low-dose whole-body γ-irradiations in 4 week-old mice resulting in the development of T-NHL mimicking human peripheral T-cell lymphoma. We utilized mice harbouring loxP-flanked Mcl-1 or loxP-flanked Bcl-x(L) in combination with inducible Cre recombinase to conditionally delete the gene of interest after lymphoma induction. Interestingly, conditional deletion of only one allele of Mcl-1 in fully established primary T-NHL cells ex vivo led to a significant and specific loss of viability, whereas survival remained unaffected by full deletion of Bcl-x(L). Reduced MCL-1 levels resulted in substantially elevated sensitivity to standard chemotherapeutics such as anthracyclins, cyclophosphamide and etoposide. In addition, mono-allelic deletion of Mcl-1 in vivo prolonged survival of lymphoma-bearing mice. Together, these data argue that anti-apoptotic MCL-1 is the single most important BCL-2 family member involved in the sustained survival of T-NHL. Disclosures: Strasser: Genentech Inc: Consultancy.

scholarly journals Competitive Endogenous RNA Network Involving miRNA and lncRNA in Non-Hodgkin Lymphoma: Current Advances and Clinical Perspectives

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1934
Author(s):  
Mara Fernandes ◽  
Herlander Marques ◽  
Ana Luísa Teixeira ◽  
Rui Medeiros
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
B Cell Lymphoma ◽  
Prognostic Biomarkers ◽  
Special Focus ◽  
Non Hodgkin Lymphoma ◽  
Clinical Biomarkers

Non-Hodgkin lymphoma (NHL) is a heterogeneous malignancy with variable patient outcomes. There is still a lack of understanding about the different players involved in lymphomagenesis, and the identification of new diagnostic and prognostic biomarkers is urgent. MicroRNAs and long non-coding RNAs emerged as master regulators of B-cell development, and their deregulation has been associated with the initiation and progression of lymphomagenesis. They can function by acting alone or, as recently proposed, by creating competing endogenous RNA (ceRNA) networks. Most studies have focused on individual miRNAs/lncRNAs function in lymphoma, and there is still limited data regarding their interactions in lymphoma progression. The study of miRNAs’ and lncRNAs’ deregulation in NHL, either alone or as ceRNAs networks, offers new insights into the molecular mechanisms underlying lymphoma pathogenesis and opens a window of opportunity to identify potential diagnostic and prognostic biomarkers. In this review, we summarized the current knowledge regarding the role of miRNAs and lncRNAs in B-cell lymphoma, including their interactions and regulatory networks. Finally, we summarized the studies investigating the potential of miRNAs and lncRNAs as clinical biomarkers, with a special focus on the circulating profiles, to be applied as a non-invasive, easy-to-obtain, and reproducible liquid biopsy for dynamic management of NHL patients.

Disruption of the SUMO Pathway in a High-Risk B-Cell Non-Hodgkin Lymphoma Pedigree

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2682-2682
Author(s):  
Cassandra Garner ◽  
Martha Glenn ◽  
Rosalie G Waller ◽  
Venkatesh Rajamanickam ◽  
Todd Darlington ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Genetic Variants ◽  
Molecular Mechanisms ◽  
Rare Variants ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Non Hodgkin Lymphoma ◽  
Sumo Pathway

Abstract Taken together, B-cell lymphoproliferative disorders (lymphoma, multiple myeloma and leukemia) are the fourth most common form of cancer. Chronic Lymphocytic Leukemia (CLL), a specific sub-type of B-cell non-Hodgkin lymphoma (NHL), is the most common adult leukemia in Western countries. Despite its prevalence, the underlying genetic mechanisms responsible for CLL remain largely unknown. The strong familial clustering seen in CLL suggests that genetic variants contributing to its pathogenesis may be inherited. Our lab is dedicated to identifying inherited genetic risk variants associated with hematological malignancies with a specific focus on CLL. We hypothesize that there are multiple germline genetic variants (both common and rare) involved in risk of CLL. In order to identify rare variants, our lab uses the Utah Population Database (UPDB) to identify extended high-risk pedigrees with statistical excess of familial CLL. We then use next generation sequencing to identify genetic variants segregating in these high-risk pedigrees. This powerful study design for identifying rare variants and has previously been proven successful for identifying variants associated with other cancers. We have performed whole-exome sequencing in one particularly high-risk pedigree containing 3 CLL cases and a mantle cell lymphoma case within 2 generations. We have identified variants in multiple genes associated with the SUMO pathway. We find rare variants in RANBP2, SP100, PML, IL1RL2 (paralog of IL1R) and CREBRF (transcriptional regulation through RNA pol II) that are shared by all NHL cases in this pedigree. Other genes in this pathway have been identified by previous CLL genome wide association studies, specifically FAS, TNF and SUMO1. Furthermore, a strong role has been previously suggested for the SUMO pathway in cancer cell survival and tumor progression, lending support to the potential role of this pathway in NHL risk. We are currently validating our sequence findings and determining the prevalence of these variants in other NHL cases included in the UPDB. Our high-risk pedigree findings are supportive that disruption of the SUMO pathway contributes to pathogenesis of NHL. Identification of the specific variants involved will increase our understanding of the molecular mechanisms contributing to NHL and has the potential to provide genetic markers that can be used for diagnosis and new avenues for treatment of these diseases. Disclosures No relevant conflicts of interest to declare.

Studies on relativity of p73 gene methylation and non-Hodgkin lymphoma

2010 ◽  
Vol 34 (8) ◽  
pp. S48-S48
Author(s):  
Jing‑Hong Pei ◽  
Sai‑Qun Luo ◽  
Jiang‑Hua Chen ◽  
Hua‑Wu Xiao ◽  
Wei‑Xin Hu
Keyword(s):  
Hodgkin Lymphoma ◽  
Gene Methylation ◽  
Non Hodgkin Lymphoma ◽  
P73 Gene

Evaluation of R-CHOP and R-CVP in the treatment of elderly patient with non-Hodgkin lymphoma

MedPharmRes ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. 1-6
Author(s):  
Truc Phan ◽  
Tram Huynh ◽  
Tuan Q. Tran ◽  
Dung Co ◽  
Khoi M. Tran
Keyword(s):  
Elderly Patients ◽  
Hodgkin Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
The Elderly ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Common Sign ◽  
Related Mortality

Introduction: Little information is available on the outcomes of R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) and R-CVP (rituximab with cyclophosphamide, vincristine and prednisone) in treatment of the elderly patients with non-Hodgkin lymphoma (NHL), especially in Vietnam. Material and methods: All patients were newly diagnosed with CD20-positive non-Hodgkin lymphoma (NHL) at Blood Transfusion and Hematology Hospital, Ho Chi Minh city (BTH) between 01/2013 and 01/2018 who were age 60 years or older at diagnosis. A retrospective analysis of these patients was perfomed. Results: Twenty-one Vietnamese patients (6 males and 15 females) were identified and the median age was 68.9 (range 60-80). Most of patients have comorbidities and intermediate-risk. The most common sign was lymphadenopathy (over 95%). The proportion of diffuse large B cell lymphoma (DLBCL) was highest (71%). The percentage of patients reaching complete response (CR) after six cycle of chemotherapy was 76.2%. The median follow-up was 26 months, event-free survival (EFS) was 60% and overall survival (OS) was 75%. Adverse effects of rituximab were unremarkable, treatment-related mortality accounted for less than 10%. There was no difference in drug toxicity between two regimens. Conclusions: R-CHOP, R-CVP yielded a good result and acceptable toxicity in treatment of elderly patients with non-Hodgkin lymphoma. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive complete response rate.

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