Non-Hodgkin lymphoma of the thyroid in a patient with hyperthyroidism.
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ABSTRACT:
SUBMITTER: Lanham T
PROVIDER: S-EPMC7850466 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNon-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes.MethodsWe pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case-control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE).ResultsRisks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10(-4)), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10(-4)). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.ConclusionsUsing a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility.
| S-EPMC4155467 | biostudies-literature
Project description:Classical Hodgkin lymphoma (cHL) is characterized by nearly universal genetic alterations in 9p24.1, resulting in constitutive expression of PD-1 ligands. This likely underlies the unique sensitivity of cHL to PD-1 blockade, with response rates of ?70% in relapsed/refractory disease. There are now numerous clinical trials testing PD-1 inhibitors in earlier stages of treatment and in combination with many other therapies. In general, non-Hodgkin lymphomas (NHLs) do not display a high frequency of 9p24.1 alterations and do not share cHL's vulnerability to PD-1 blockade. However, a few entities have genetic or immunologic features that may predict sensitivity to immune checkpoint blockade. These include primary mediastinal B cell lymphoma, primary central nervous system lymphoma, and primary testicular lymphoma, which harbor frequent alterations in 9p24.1, as well as Epstein Barr virus (EBV)-infected lymphomas, where EBV infection leads to increased PD-L1 expression. Although these subtypes may be specifically vulnerable to PD-1 blockade, the majority of NHLs appear to be minimally sensitive to PD-1 blockade monotherapy. Current investigations in NHL are therefore focusing on targeting other checkpoints or studying PD-1-based combination therapy. Looking forward, additional insight into the most common mechanisms of resistance to immune checkpoint inhibitors will be important to guide rational clinical trial design. In this review, we describe the biological basis for checkpoint blockade in cHL and NHL and summarize the clinical data generated to date. Guided by our rapidly evolving understanding of the pathobiology of various lymphoma subtypes, we are hopeful that the role of checkpoint inhibitors in lymphoma treatment will continue to grow.
| S-EPMC5728646 | biostudies-literature
Project description:Reed-Sternberg cells (RSCs) are hallmarks of classic Hodgkin lymphoma (cHL). However, cells with a similar morphology and immunophenotype, so-called Reed-Sternberg-like cells (RSLCs), are occasionally seen in both B cell and T cell non-Hodgkin Lymphomas (NHLs). In NHLs, RSLCs are usually present as scattered elements or in small clusters, and the typical background microenviroment of cHL is usually absent. Nevertheless, in NHLs, the phenotype of RSLCs is very similar to typical RSCs, staining positive for CD30 and EBV, and often for B cell lineage markers, and negative for CD45/LCA. Due to different therapeutic approaches and prognostication, it is mandatory to distinguish between cHL and NHLs. Herein, NHL types in which RSLCs can be detected along with clinicopathological correlation are described. Moreover, the main helpful clues in the differential diagnosis with cHL are summarized.
| S-EPMC7760963 | biostudies-literature
Project description:MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression by binding to the 3'-UTR of their target genes, can act as oncogenes or tumor suppressors. Recently, other types of non-coding RNAs-piwiRNAs and long non-coding RNAs-have also been identified. Hodgkin lymphoma (HL) is a B cell origin disease characterized by the presence of only 1% of tumor cells, known as Hodgkin and Reed-Stenberg (HRS) cells, which interact with the microenvironment to evade apoptosis. Several studies have reported specific miRNA signatures that can differentiate HL lymph nodes from reactive lymph nodes, identify histologic groups within classical HL, and distinguish HRS cells from germinal center B cells. Moreover, some signatures are associated with survival or response to chemotherapy. Most of the miRNAs in the signatures regulate genes related to apoptosis, cell cycle arrest, or signaling pathways. Here we review findings on miRNAs in HL, as well as on other non-coding RNAs.
| S-EPMC5485978 | biostudies-literature
Project description:INTRODUCTION: Despite decades of intensive research, Non-Hodgkin Lymphoma (NHL) remains poorly understood and is largely incurable. NHL is a heterogeneous group of malignancies with multiple subtypes, each of which has distinct morphologic, immunophenotypic, and clinical features. Identifying the risk factors for NHL may improve our understanding of the underlying biological mechanisms and have an impact on clinical practice. AREAS COVERED: This article provides a review of several aspects of NHL, including epidemiology and subtype classification, clinical, environmental, genetic, and genomic risk factors identified for etiology and prognosis, and available statistical and bioinformatics tools for identification of genetic and genomic risk factors from the analysis of high-throughput studies. EXPERT OPINION: Multiple clinical and environmental risk factors have been identified. However, they have failed to provide practically effective prediction. Genetic and genomic risk factors identified from high-throughput studies have suffered a lack of reproducibility. The identification of genetic/genomic risk factors demands innovative statistical and bioinformatics tools. Although multiple analysis methods have been developed, there is still room for improvement. There is a critical need for well-designed, prospective, large-scale pangenomic studies.
| S-EPMC3205981 | biostudies-literature
Project description:BACKGROUND: Epigenetic inactivation of tumor suppressor genes (TSG) by promoter CpG island hypermethylation is a hallmark of cancer. To assay its extent in human lymphoma, methylation of 24 TSG was analyzed in lymphoma-derived cell lines as well as in patient samples. METHODS: We screened for TSG methylation using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in 40 lymphoma-derived cell lines representing anaplastic large cell lymphoma, Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Hodgkin lymphoma and mantle cell lymphoma (MCL) as well as in 50 primary lymphoma samples. The methylation status of differentially methylated CD44 was verified by methylation-specific PCR and bisulfite sequencing. Gene expression of CD44 and its reactivation by DNA demethylation was determined by quantitative real-time PCR and on the protein level by flow cytometry. Induction of apoptosis by anti-CD44 antibody was analyzed by annexin-V/PI staining and flow cytometry. RESULTS: On average 8 ± 2.8 of 24 TSG were methylated per lymphoma cell line and 2.4 ± 2 of 24 TSG in primary lymphomas, whereas 0/24 TSG were methylated in tonsils and blood mononuclear cells from healthy donors. Notably, we identified that CD44 was hypermethylated and transcriptionally silenced in all BL and most FL and DLBCL cell lines, but was usually unmethylated and expressed in MCL cell lines. Concordant results were obtained from primary lymphoma material: CD44 was not methylated in MCL patients (0/11) whereas CD44 was frequently hypermethylated in BL patients (18/29). In cell lines with CD44 hypermethylation, expression was re-inducible at mRNA and protein levels by treatment with the DNA demethylating agent 5-Aza-2'-deoxycytidine, confirming epigenetic regulation of CD44. CD44 ligation assays with a monoclonal anti-CD44 antibody showed that CD44 can mediate apoptosis in CD44+ lymphoma cells. CD44 hypermethylated, CD44- lymphoma cell lines were consistently resistant towards anti-CD44 induced apoptosis. CONCLUSION: Our data show that CD44 is epigenetically regulated in lymphoma and undergoes de novo methylation in distinct lymphoma subtypes like BL. Thus CD44 may be a promising new epigenetic marker for diagnosis and a potential therapeutic target for the treatment of specific lymphoma subtypes.
| S-EPMC2955612 | biostudies-literature
Project description:There has been a recent emergence of novel targeted agents for treatment of Hodgkin and non-Hodgkin lymphoma. In particular, antibodies and antibody-drug conjugates directed against surface antigens, agents that block immune checkpoint pathways, and small molecule inhibitors directed against cell signaling pathways have shown significant promise in patients with relapsed and refractory disease and in the frontline setting. With the development of these new therapies, cytotoxic chemotherapy may be avoided entirely in some clinical settings. This review will present the latest information on these novel treatments in Hodgkin and non-Hodgkin lymphoma and will discuss both recently approved agents as well as drugs currently being studied in clinical trials.
| S-EPMC4588185 | biostudies-literature
Project description:Infectious etiologies have been hypothesized for Hodgkin and non-Hodgkin lymphoma (HL and NHL) in early life, but findings to date for specific lymphomas and periods of susceptibility are conflicting. We conducted the first national cohort study to examine whether season of birth, a proxy for infectious exposures in the first few months of life, is associated with HL or NHL in childhood through young adulthood. A total of 3,571,574 persons born in Sweden in 1973-2008 were followed up through 2009 to examine the association between season of birth and incidence of HL (943 cases) or NHL (936 cases). We found a sinusoidal pattern in NHL risk by season of birth (p?=?0.04), with peak risk occurring among birthdates in April. Relative to persons born in fall (September-November), odds ratios for NHL by season of birth were 1.25 [95% confidence interval (CI), 1.04-1.50; p?=?0.02] for spring (March-May), 1.22 (95% CI, 1.01-1.48; p?=?0.04) for summer (June-August) and 1.11 (95% CI, 0.91-1.35; p?=?0.29) for winter (December-February). These findings did not vary by sex, age at diagnosis or major subtypes. In contrast, there was no seasonal association between birthdate and risk of HL (p?=?0.78). In this large cohort study, birth in spring or summer was associated with increased risk of NHL (but not HL) in childhood through young adulthood, possibly related to immunologic effects of delayed infectious exposures compared with fall or winter birth. These findings suggest that immunologic responses in early infancy may play an important role in the development of NHL.
| S-EPMC4165654 | biostudies-literature
Project description:Understanding patterns of etiologic commonality and heterogeneity for non-Hodgkin lymphomas may illuminate lymphomagenesis. We present the first systematic comparison of risks by lymphoma subtype for a broad range of putative risk factors in a population-based case-control study, including diffuse large B-cell (DLBCL; N = 416), follicular (N = 318), and marginal zone lymphomas (N = 106), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; N = 133). We required at least 2 of 3 analyses to support differences in risk: (1) polytomous logistic regression, (2) homogeneity tests, or (3) dichotomous logistic regression, analyzing all 7 possible pairwise comparisons among the subtypes, corresponding to various groupings by clinical behavior, genetic features, and differentiation. Late birth order and high body mass index (>/= 35) kg/m(2)) increased risk for DLBCL alone. Autoimmune conditions increased risk for marginal zone lymphoma alone. The tumor necrosis factor G-308A polymorphism (rs1800629) increased risks for both DLBCL and marginal zone lymphoma. Exposure to certain dietary heterocyclic amines from meat consumption increased risk for CLL/SLL alone. We observed no significant risk factors for follicular lymphoma alone. These data clearly support both etiologic commonality and heterogeneity for lymphoma subtypes, suggesting that immune dysfunction is of greater etiologic importance for DLBCL and marginal zone lymphoma than for CLL/SLL and follicular lymphoma.
| S-EPMC2597610 | biostudies-literature
Project description:Recent studies have shown that persistent SARS-CoV-2 infections in immunocompromised patients can trigger the accumulation of an unusual high number of mutations with potential relevance at both biological and epidemiological levels. Here, we report a case of an immunocompromised patient (non-Hodgkin lymphoma patient under immunosuppressive therapy) with a persistent SARS-CoV-2 infection (marked by intermittent positivity) over at least 6 months. Viral genome sequencing was performed at days 1, 164, and 171 to evaluate SARS-CoV-2 evolution. Among the 15 single-nucleotide polymorphisms (SNPs) (11 leading to amino acid alterations) and 3 deletions accumulated during this long-term infection, four amino acid changes (V3G, S50L, N87S, and A222V) and two deletions (18-30del and 141-144del) occurred in the virus Spike protein. Although no convalescent plasma therapy was administered, some of the detected mutations have been independently reported in other chronically infected individuals, which supports a scenario of convergent adaptive evolution. This study shows that it is of the utmost relevance to monitor the SARS-CoV-2 evolution in immunocompromised individuals, not only to identify novel potentially adaptive mutations, but also to mitigate the risk of introducing "hyper-evolved" variants in the community. IMPORTANCE Tracking the within-patient evolution of SARS-CoV-2 is key to understanding how this pandemic virus shapes its genome toward immune evasion and survival. In the present study, by monitoring a long-term COVID-19 immunocompromised patient, we observed the concurrent emergence of mutations potentially associated with immune evasion and/or enhanced transmission, mostly targeting the SARS-CoV-2 key host-interacting protein and antigen. These findings show that the frequent oscillation in the immune status in immunocompromised individuals can trigger an accelerated virus evolution, thus consolidating this study model as an accelerated pathway to better understand SARS-CoV-2 adaptive traits and anticipate the emergence of variants of concern.
| S-EPMC8386466 | biostudies-literature