Viral Agents as Potential Drivers of Diffuse Large B-Cell Lymphoma Tumorigenesis

Bilajac, Esma; Mahmutović, Lejla; Lundström, Kenneth; Glamočlija, Una; Šutković, Jasmin; Sezer, Abas; Hromić‐Jahjefendić, Altijana

doi:10.3390/v14102105

Cited by 5 publications

(2 citation statements)

References 207 publications

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“…The majority of patients in our cohort were younger than suggested by epidemiologic studies in Western countries. 12,13 This might be attributable to the younger population pyramid, the oncogenic potential of childhood infections, 14 and reduced referral of elderly patients; however, more epidemiologic data are needed to prove or refute these Overall Survival (days) possibilities. Studies from India have also documented a younger median age of the presentation, 15 similar to our data.…”

Section: Discussionmentioning

confidence: 99%

Real-World Challenges of Managing Diffuse Large B-Cell Lymphoma in a Developing Country

Iftikhar,

Ahmad,

Haider

et al. 2024

JCO Glob Oncol

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PURPOSE To highlight challenges and cancer care disparities in patients of diffuse large B-cell lymphoma management in resource-constrained settings. MATERIALS AND METHODS This multicenter retrospective study included 738 patients from 12 public and private sector hematology-oncology centers across Pakistan. Patients were divided into limited-resource and enhanced-resource settings as per national diffuse large B-cell lymphoma (DLBCL) guidelines. RESULTS The median age at diagnosis was 47 years (range, 14-89). Male:female ratio was 2.5:1. Majority of the patients (69.3%) were treated in limited-resource settings. Computed tomography was used as a staging modality in 442 (60%) patients. Limited-stage DLBCL was present in 13.5% of patients, while 86.3% had advanced-stage disease at diagnosis. First-line regimens included rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in 56% and cyclophosphamide, doxorubicin, vincristine, prednisone in 34% of patients, while 10% of patients received palliative regimens upfront. Of evaluable data, complete remission was documented in 299 (74.4%) patients, 39 (9.8%) had partial response and 63 (13.5%) had progressive disease. Disease-free survival (DFS) and overall survival (OS) status were not available for 345 (46.8%) patients at the time of data collection. Overall study cohort had a median follow-up of 2.2 years with a median OS of 3.6 years (95% CI, 3.1 to 4.1), median DFS of 3.1 years (95% CI, 2.6 to 3.6), and a 5-year OS of 40% and DFS of 36%. CONCLUSION Patients from low- and middle-income countries present at an earlier age and have more advanced disease. Patients were frequently lost to follow-up, and record keeping was inadequate more so in patients treated in limited-resource settings. There is a need to establish a national lymphoma registry, improve record keeping, and standardize treatments to ensure improvement in treatment outcomes.

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Section: Discussionmentioning

confidence: 99%

Real-World Challenges of Managing Diffuse Large B-Cell Lymphoma in a Developing Country

Iftikhar,

Ahmad,

Haider

et al. 2024

JCO Glob Oncol

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“…Viral agents are regarded as potential drivers of DLBCL tumorigenesis [ 206 , 207 ]. Various reports suggest an association of viral infections with DLBCL, including Epstein–Barr virus (EBV) also known as human herpes virus 4 (HHV4) [ 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 ], human immunodeficiency virus HIV (HIV) [ 217 , 218 , 219 , 220 , 221 ], hepatitis B virus (HBV) [ 222 , 223 , 224 , 225 , 226 ], hepatitis C virus (HCV) [ 227 , 228 , 229 ], human T-cell leukemia virus type 1 (HTLV-1) [ 230 ], and Simian virus 40 (SV40) infections [ 231 , 232 , 233 ], while human herpes virus 8 (HHV8) also known as Kaposi sarcoma-associated herpesvirus (KSHV) [ 30 , 234 , 235 , 236 ] and human papilloma virus (HPV) [ 237 , 238 ] associations with DLBCL are only rarely observed.…”

Section: Potential Milk-related Factors Promoting Dlbclmentioning

confidence: 99%

Potential Pathogenic Impact of Cow’s Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma

Melnik

Stadler

Weiskirchen

et al. 2023

IJMS

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Epidemiological evidence supports an association between cow’s milk consumption and the risk of diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma worldwide. This narrative review intends to elucidate the potential impact of milk-related agents, predominantly milk-derived exosomes (MDEs) and their microRNAs (miRs) in lymphomagenesis. Upregulation of PI3K-AKT-mTORC1 signaling is a common feature of DLBCL. Increased expression of B cell lymphoma 6 (BCL6) and suppression of B lymphocyte-induced maturation protein 1 (BLIMP1)/PR domain-containing protein 1 (PRDM1) are crucial pathological deviations in DLBCL. Translational evidence indicates that during the breastfeeding period, human MDE miRs support B cell proliferation via epigenetic upregulation of BCL6 (via miR-148a-3p-mediated suppression of DNA methyltransferase 1 (DNMT1) and miR-155-5p/miR-29b-5p-mediated suppression of activation-induced cytidine deaminase (AICDA) and suppression of BLIMP1 (via MDE let-7-5p/miR-125b-5p-targeting of PRDM1). After weaning with the physiological termination of MDE miR signaling, the infant’s BCL6 expression and B cell proliferation declines, whereas BLIMP1-mediated B cell maturation for adequate own antibody production rises. Because human and bovine MDE miRs share identical nucleotide sequences, the consumption of pasteurized cow’s milk in adults with the continued transfer of bioactive bovine MDE miRs may de-differentiate B cells back to the neonatal “proliferation-dominated” B cell phenotype maintaining an increased BLC6/BLIMP1 ratio. Persistent milk-induced epigenetic dysregulation of BCL6 and BLIMP1 expression may thus represent a novel driving mechanism in B cell lymphomagenesis. Bovine MDEs and their miR cargo have to be considered potential pathogens that should be removed from the human food chain.

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The Clinical Significance and Prognostic Role of Whole-Blood Epstein-Barr Virus DNA in Lymphoma-Associated Hemophagocytic Lymphohistiocytosis

et al. 2023

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Purpose: To evaluate the role of circulating Epstein-Barr virus (EBV) DNA in lymphoma-associated hemophagocytic lymphohistiocytosis.Methods: We retrospectively analyzed 306 adult patients with lymphoma-associated hemophagocytic lymphohistiocytosis admitted to the First A liated Hospital of Nanjing Medical University from August 2009 to November 2022.Results: T/NK-cell malignancies (54.3%, 166/306) were the most common subtypes, followed by B-cell non-Hodgkin lymphoma (38.2%, 117/306). Elevated whole-blood EBV DNA was observed in 55.8% (164/294) of the patients and the median number was signi cantly higher in the T/NK malignancies (199500, than that in the B-cell non-Hodgkin lymphoma (5520, 1240-28400, P < 0.001).The optimum cutoff value for the overall survival of EBV DNA was determined as 43600 copies/mL. Compared to the patients with EBV DNA ≤ 43600 copies/mL, those with EBV DNA > 43600 copies/mL were younger and had more T/NK-cell malignancies, more bone marrow in ltration, lower levels of neutrophils and brinogen, and higher levels of alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, triacylglycerol, and β 2 -microglobulin. A higher load of EBV DNA (> 43600 copies/mL), thrombocytopenia (< 100×10 9 /L), neutropenia (< 1×10 9 /L), hypo brinogenemia (≤ 1.5 g/L), and elevated levels of creatinine (> 133 μmol/L) were independent adverse predictors of overall survival. A prognostic index based on EBV DNA and the other four factors was established to categorize the patients into four groups with signi cantly different outcomes. Conclusion:Our study identi ed high EBV load as a risk factor for lymphoma-associated HLH and established a prognostic index based on EBV DNA to predict patients' outcomes.

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Viral Agents as Potential Drivers of Diffuse Large B-Cell Lymphoma Tumorigenesis

Cited by 5 publications

References 207 publications

Real-World Challenges of Managing Diffuse Large B-Cell Lymphoma in a Developing Country

Real-World Challenges of Managing Diffuse Large B-Cell Lymphoma in a Developing Country

Potential Pathogenic Impact of Cow’s Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma

The Clinical Significance and Prognostic Role of Whole-Blood Epstein-Barr Virus DNA in Lymphoma-Associated Hemophagocytic Lymphohistiocytosis

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