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This letter to the editor published in the journal Leukemia & Lymphoma discusses the challenges in diagnosing Burkitt lymphoma (BL) and the results of a study on the diagnostic concordance for BL among experienced hematopathologists. The study found that initial consensus for BL diagnosis was low, but improved with additional information from immunohistochemistry and clinical data. The letter emphasizes the need for additional techniques to improve the reliability of distinguishing BL from other lymphomas and highlights the importance of multidisciplinary meetings for accurate diagnosis and treatment decisions. References to previous studies and classifications of lymphomas are provided for further research. [Extracted from the article]

Lectins are carbohydrate‐binding proteins, whose biological effects are exerted via binding to glycoconjugates expressed on the surface of cells. Exposure to lectins can lead not only to a change in the structure and properties of cells but also to their death. Here, we studied the biological activity of lectins from the mussels Crenomytilus graynus (CGL) and Mytilus trossulus (MTL) and showed that these proteins can affect the proliferation of human lymphoma cells. Both lectins suppressed the formation of colonies as well as cell cycle progression. The mechanism of action of these lectins was not mediated by reactive oxygen species but included damaging of mitochondria, inhibition of key cell cycle points, and activation of MAPK signaling pathway in tumor cells. Computer modeling suggested that various effects of CGL and MTL on lymphoma cells may be due to the difference in the energy of binding of these lectins to carbohydrate ligands on the cell surface. Thus, molecular recognition of residues of terminal carbohydrates on the surface of tumor cells is a key factor in the manifestation of the biological action of lectins. [ABSTRACT FROM AUTHOR]

Multiple myeloma is the second most hematological cancer. RUVBL1 and RUVBL2 form a subcomplex of many chromatin remodeling complexes implicated in cancer progression. As an inhibitor specific to the RUVBL1/2 complex, CB-6644 exhibits remarkable anti-tumor activity in xenograft models of Burkitt's lymphoma and multiple myeloma (MM). In this work, we defined transcriptional signatures corresponding to CB-6644 treatment in MM cells and determined underlying epigenetic changes in terms of chromatin accessibility. CB-6644 upregulated biological processes related to interferon response and downregulated those linked to cell proliferation in MM cells. Transcriptional regulator inference identified E2Fs as regulators for downregulated genes and MED1 and MYC as regulators for upregulated genes. CB-6644-induced changes in chromatin accessibility occurred mostly in non-promoter regions. Footprinting analysis identified transcription factors implied in modulating chromatin accessibility in response to CB-6644 treatment, including ATF4/CEBP and IRF4. Lastly, integrative analysis of transcription responses to various chemical compounds of the molecular signature genes from public gene expression data identified CB-5083, a p97 inhibitor, as a synergistic candidate with CB-6644 in MM cells, but experimental validation refuted this hypothesis. [ABSTRACT FROM AUTHOR]

This article explores the prevalence of herpesviruses among the Yanomami indigenous people and its connection to Heck's disease. The study collected saliva samples from 81 individuals from the Yanomami ethnic group and analyzed them for human herpesviruses. The results revealed that several individuals tested positive for various herpesviruses, including HSV-1, EBV, CMV, HHV-6, HHV-7, and HHV-8. The study also found a significant correlation between the presence of Heck's disease and HHV-6 and HSV-1. These findings emphasize the importance of understanding the impact of viruses on indigenous populations and their unique manifestations. The study further examined the prevalence of herpesviruses among the Yanomami indigenous people and its association with Heck's disease. The results indicated that there was no significant difference in the presence of lesions during childhood compared to adolescence and adulthood. However, the disease typically begins before the age of 20 and spontaneously regresses over time. The study also discovered a rare connection between the development of Heck's disease and the presence of EBV, likely due to immunosuppression. Additionally, there was an association between Heck's disease and HSV-1, which is not commonly reported in the literature. This research underscores the need for greater understanding of how these microorganisms behave in indigenous populations and the development of public health policies to address the oral and periodontal conditions of indigenous people. [Extracted from the article]

Introduction: Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma associated with Plasmodium falciparum and Epstein-Barr virus, both of which affect metabolic pathways. The metabolomic patterns of BL is unknown. Materials and methods: We measured 627 metabolites in pre-chemotherapy treatment plasma samples from 25 male children (6–11 years) with BL and 25 cancer-free area- and age-frequency-matched male controls from the Epidemiology of Burkitt Lymphoma in East African Children and Minors study in Uganda using liquid chromatography-tandem mass spectrometry. Unconditional, age-adjusted logistic regression analysis was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for the BL association with 1-standard deviation increase in the log-metabolite concentration, adjusting for multiple comparisons using false discovery rate (FDR) thresholds and Bonferroni correction. Results: Compared to controls, levels for 42 metabolite concentrations differed in BL cases (FDR < 0.001), including triacylglyceride (18:0_38:6), alpha-aminobutyric acid (AABA), ceramide (d18:1/20:0), phosphatidylcholine ae C40:6 and phosphatidylcholine C38:6 as the top signals associated with BL (ORs = 6.9 to 14.7, P < 2.4✕10− 4). Two metabolites (triacylglyceride (18:0_38:6) and AABA) selected using stepwise logistic regression discriminated BL cases from controls with an area under the curve of 0.97 (95% CI: 0.94, 1.00). Conclusion: Our findings warrant further examination of plasma metabolites as potential biomarkers for BL risk/diagnosis. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of Kikuchi-Fujimoto disease (KFD) with gluteal myositis. KFD is a self-limiting disease characterized by fever and cervical lymphadenopathy, but in this case, the patient presented with persistent fever and right hip pain. The article explores possible mechanisms for the association between KFD and gluteal myositis, including concomitant infective myositis, autoimmune disease-related myositis, and extranodal involvement. The authors emphasize the importance of considering KFD in patients with unknown fever origins, even if the clinical findings appear unrelated to KFD. [Extracted from the article]

Introduction: Cancer is the second leading cause of mortality with over 19 million cases and 10 million deaths worldwide. Available data on cancer patterns in Uganda are through modelling of data from two population-based cancer registries (PBCRs) representing only about 10% of the cancer situation in Uganda. This study sought to determine the common types of cancer among adults and children in Arua District over a 5-year period (2017–2021). Methods: Retrospective cohort chart review and ‘catchment population approach’ were employed. All newly diagnosed cancer patients from Arua between 2017 and 2021 were included in this study. Data were collected using Redcap whereas management and analysis were conducted using Stata 17. Cancer patterns were computed as frequencies and percentages and the interest was in finding out the common cancers among adults (above 19 years) and children (0–19 years). Results: Over the 5-year study period, a total of 1,118 new cancer cases were registered, with slightly more females (52.1%). The top five common cancers irrespective of sex and age were: liver cancer (13.7%), cervical (11.8%), breast (10.7%), oesophagus (10.5%) and Burkitt’s lymphoma (BL) (6.4%). In this study, 15.3% (n = 171) of the study participants were children. The top five common childhood cancers included BL (42%), leukemia (10.5%), other lymphomas (9.4%), osteosarcoma (4.7%) and nephroblastoma (3%). Conclusion: There is a high incidence of liver cancer in Arua district. The high levels of cervical, breast and oesophagus cancer were consistent with what is reported by the two PBCRs in Uganda. However, BL could be due to the presence of a BL treatment centre at Kuluva hospital in Arua. Cancer interventions in Arua should therefore be targeted towards liver, cervix, breast, and oesophagus cancer and furthering research on the reason for the high incidence of liver cancer. [ABSTRACT FROM AUTHOR]

Breast lymphomas are rare, malignant breast neoplasms with a heterogeneous pattern of clinical symptoms. Burkitt's lymphoma is a rare, highly aggressive, and rapidly growing B-cell non-Hodgkin lymphoma. We report about a 27-year-old woman diagnosed as having secondary breast Burkitt's lymphoma, probably originating from the stomach, with multiple distant metastases. Breast ultrasonography revealed multiple, variable sized, heterogeneous masses with posterior acoustic enhancement and echogenic rims. These imaging findings may sometimes overlap with those of other breast malignancies. However, unlike other breast malignancies, lymphoma can be diagnosed by biopsy and does not require surgical excision. To avoid unnecessary treatment, radiologists and clinicians should be aware of the characteristic imaging features of breast lymphomas. [ABSTRACT FROM AUTHOR]

Most mature B-cell malignancies originate from the malignant transformation of germinal center (GC) B cells. The GC reaction appears to have a role in malignant transformation, in which a major player of the GC reaction is BCL6, a key regulator of this process. We now demonstrate that BCL6 protein levels were dramatically decreased in Epstein-Barr virus (EBV)-positive lymphoblastoid cell lines and Burkitt’s lymphoma cell lines. Notably, BCL6 degradation was significantly enhanced in the presence of both EBNA3C and FBXO11. Furthermore, the amino-terminal domain of EBNA3C, which contains residues 50–100, interacts directly with FBXO11. The expression of EBNA3C and FBXO11 resulted in a significant induction of cell proliferation. Furthermore, BCL6 protein expression levels were regulated by EBNA3C via the Skp Cullin Fbox (SCF)FBXO11 complex, which mediated its ubiquitylation, and knockdown of FBXO11 suppressed the transformation of lymphoblastoid cell lines. These data provide new insights into the function of EBNA3C in B-cell transformation during GC reaction and raise the possibility of developing new targeted therapies against EBV-associated cancers. IMPORTANCE The novel revelation in our study involves the suppression of BCL6 expression by the essential Epstein-Barr virus (EBV) antigen EBNA3C, shedding new light on our current comprehension of how EBV contributes to lymphomagenesis by impeding the germinal center reaction. It is crucial to note that while several EBV latent proteins are expressed in infected cells, the collaborative mechanisms among these proteins in regulating B-cell development or inducing B-cell lymphoma require additional investigation. Nonetheless, our findings carry significance for the development of emerging strategies aimed at addressing EBV-associated cancers. [ABSTRACT FROM AUTHOR]

Intestinal obstruction is a surgical emergency frequently encountered in routine practice, usually caused by abdominal adhesions. Although extra nodal lymphoma is most often localized in the gastrointestinal tract and may be responsible for intestinal obstruction, Burkitt's lymphoma is a very rare cause in adults.We report a case of Burkitt's lymphoma mimicking an intestinal obstruction in a 48-year-old adult who presented with an obstructive syndrome and altered general condition.Imaging and anatomopathological examination after immunohistochemical analysis concluded to a multi-systemic Burkitt's lymphoma.Chemotherapy was immediately started with complete remission.

Reactivation from latency plays a significant role in maintaining persistent lifelong Epstein-Barr virus (EBV) infection. Mechanisms governing successful activation and progression of the EBV lytic phase are not fully understood. EBV expresses multiple viral microRNAs (miRNAs) and manipulates several cellular miRNAs to support viral infection. To gain insight into the host miRNAs regulating transitions from EBV latency into the lytic stage, we conducted a CRISPR/Cas9-based screen in EBV+ Burkitt lymphoma (BL) cells using anti-Ig antibodies to crosslink the B cell receptor (BCR) and induce reactivation. Using a gRNA library against >1500 annotated human miRNAs, we identified miR-142 as a key regulator of EBV reactivation. Genetic ablation of miR-142 enhanced levels of immediate early and early lytic gene products in infected BL cells. Ago2-PAR-CLIP experiments with reactivated cells revealed miR-142 targets related to Erk/MAPK signaling, including components directly downstream of the B cell receptor (BCR). Consistent with these findings, disruption of miR-142 enhanced SOS1 levels and Mek phosphorylation in response to surface Ig cross-linking. Effects could be rescued by inhibitors of Mek (cobimetinib) or Raf (dabrafenib). Taken together, these results show that miR-142 functionally regulates SOS1/Ras/Raf/Mek/Erk signaling initiated through the BCR and consequently, restricts EBV entry into the lytic cycle. Author summary: Epstein-Barr virus (EBV) is a common herpesvirus that infects most individuals worldwide and can persist in the body for life. Long-term viral persistence is established in part through latently infected memory B cells and periodic reactivation events which maintain viral reservoirs. To investigate functional roles for host non-coding RNAs in EBV latency and reactivation—specifically microRNAs—we conducted a genome-wide CRISPR screen in EBV-positive Burkitt's lymphoma (BL) cells. By screening >1500 human miRNAs, we identified miR-142 as a potent regulator of the lytic cycle. When miR-142 was disrupted, latently infected BL cells responded rapidly to external reactivation triggers and exhibited significantly elevated levels of lytic viral proteins. Through mechanistic studies, we found that miR-142 regulates cell signaling pathways such as the Ras/Raf/Mek/Erk pathway and can target SOS1 encoding a Ras guanine nucleotide exchange factor. Heightened EBV reactivation in miR-142 mutant cells could be reversed using chemical inhibitors to Raf, Mek, or Sos1. These findings provide novel insight into the role of miR-142 in the EBV life cycle and further unveil potential for inhibiting Sos1 as a means to suppress EBV reactivation. [ABSTRACT FROM AUTHOR]

Introduction: Burkitt's lymphoma (BL) is a non-Hodgkin B-cell lymphoma that grows aggressively. Overexpression of cyclooxygenase (Cox)-2 is known to be implicated in several cancer mechanisms including apoptosis inhibition. Meloxicam is a non-steroidal anti-inflammatory medication that selectively blocks the inducible isoform of the Cox-2 enzyme. This research aimed to examine meloxicam's effect upon Burkitt's lymphoma cells' apoptosis. Materials and methods: BL cells (ATCC-CCL- 86-lymphocyte) were exposed to meloxicam at a dose of 0 µM, 100 µM, and 200 µM for 24 hours. Phase contrast microscopy was used to evaluate the cell's morphological alterations, and apoptosis was analyzed using TUNEL assay employing flow cytometry method. Results: ANOVA showed significant differences among groups indicating that meloxicam has significantly (p<0.05) induced apoptosis of BL cells. When the LSD test was used to compare all treated cells to untreated cells, significant differences (p<0.05) were found. Conclusion: It is concluded that meloxicam induces apoptosis of BL cells. [ABSTRACT FROM AUTHOR]

Background: Biliary obstruction due to compression by a B-cell solid tumor occurs rarely. A few reports have described biliary reconstruction surgery for obstructive jaundice caused by Burkitt's lymphoma. However, there are no detailed reports on pediatric cases. We report a pediatric case of obstructive jaundice due to malignant lymphoma treated with biliary reconstruction surgery. Case presentation: A 5-year-old girl presented to our hospital with a massive abdominal tumor that caused biliary stricture. Chemotherapy was initiated after an open tumor biopsy. However, endoscopic biliary stent placement was performed owing to elevated bilirubin levels. We treated the patient with chemotherapy for 9 months while endoscopically replacing the biliary stent every few months. She achieved complete tumor remission. However, sclerotic lymph nodes were persistent on the dorsal side of the cholecystic duct junction, and biliary stricture at the same site had changed to stent-dependent biliary obstruction. Therefore, we performed choledochojejunostomy and retrocolic Roux-en-Y reconstruction 15 months after initial admission. There were no postoperative complications or tumor recurrences, and the bilirubin level remained low. Histopathologically, the resected bile duct wall was fibrotic and thick, and the bile duct lumen narrowed. Conclusions: Biliary reconstruction is effective to achieve long-term biliary patency in pediatric patients with stent-dependent biliary obstruction due to malignant lymphoma. However, the decision on when to stop biliary stent replacement and proceed to biliary reconstruction surgery is a matter of debate. Further case studies are required to address this issue. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This report highlights the risk of latent tuberculosis (TB) reactivation after treatment with Polatuzumab Vedotin (PV), Rituximab, and Bendamustine (PBR protocol) despite appropriate chemoprophylaxis. A 48‐year‐old male with refractory Burkitt's lymphoma (BKL) was treated with PBR protocol. At baseline, the patient had a negative QuantiFERON test result, which turned out to be positive prior to starting PBR. He received chemoprophylaxis for 9 months and was compliant with treatment. One year later, he was admitted with COVID‐19 pneumonia and was treated according to the protocol. His symptoms persisted for 1 month. Investigations yielded disseminated TB‐infiltrated bone marrow and pleura. Downstream B‐cell and T‐cell depletion secondary to CD20 and CD79b antagonism may potentially explain the increased risk of TB reactivation associated with the combination of PV and rituximab. Further research is necessary to monitor the risk of TB reactivation among patients receiving a combination of PV and rituximab, especially in endemic areas with high prevalence and incidence of TB. [ABSTRACT FROM AUTHOR]

Aim: This study explores changes in viral and host gene expressions during Epstein–Barr virus lytic reactivation, establishing a bioinformatics foundation for understanding the pathogenesis of Burkitt's lymphoma (BL) and identifying potential therapeutic targets. Methods: We used the data set GSE141220 to assess differentially expressed genes. Subsequent analyses included Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Hub genes were identified using Cytoscape. Results: Viral gene expression exhibited significant alterations 24 h after treatment with Sodium butyrate (NaB). Upregulated host genes mainly related to the PI3K-Akt and MAPK signaling pathways. Conclusion: Epstein–Barr virus lytic reactivation is likely to involve the activation of the PI3K-Akt and MAPK signaling pathways. Hub genes may serve as therapeutic targets for BL. Our study looks at a severe disease known as Burkitt's lymphoma that is linked to a virus called Epstein–Barr Virus. We looked at the genetic makeup of the virus to explore changes that may show why the virus becomes active after a period of inactivity. We hope this will help to identify new ways to diagnose and treat Burkitt's lymphoma. Article highlights Background Burkitt's lymphoma (BL) is closely linked to Epstein–Barr virus (EBV), with the lytic phase of EBV also potentially playing a crucial role in tumorigenesis. This study explores changes in viral and host gene expression during EBV lytic reactivation to understand BL pathogenesis and identify therapeutic targets. Methods Utilized GSE141220 data set to analyze the changes in virus and their host genes in HH514-16 cell line treated with NaB. Conducted Gene ontology (GO) functional annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. Identified hub genes using Cytoscape software. Results Viral gene expression was significantly altered 24 h after NaB treatment, with upregulated host genes associated with PI3K-Akt and MAPK signaling pathways. Latency genes showed minor changes, while lytic genes exhibited significant increases after 24 and 48 h of NaB treatment. Discussion EBV lytic reactivation impacts both viral and host gene expression, with potential implications for BL pathogenesis. Identification of hub genes such as STAT1, EGF and EGFR suggests promising targets for BL therapy. Limitations include the need for broader cell line inclusion and increased sample replicates for improved reliability. Conclusion EBV lytic reactivation may be associated with the activation of the PI3K-Akt and MAPK signaling pathways. STAT1, EGFR, EGF and other hub genes may serve as potential targets for the diagnosis and therapy of BL. [ABSTRACT FROM AUTHOR]

Epstein–Barr Virus (EBV) exists in a latent state in 90% of the world's population and is linked to numerous cancers, such as Burkitt's Lymphoma, Hodgkin's, and non-Hodgkin's Lymphoma. One EBV latency protein, latency membrane protein 2A (LMP2A), is expressed in multiple latency phenotypes. LMP2A signaling has been extensively studied and one target of LMP2A is the mammalian target of rapamycin (mTOR). Since mTOR has been linked to reprogramming tumor metabolism and increasing levels of hypoxia-inducible factor 1 α (HIF-1α), we hypothesized that LMP2A would increase HIF-1α levels to enhance ATP generation in B lymphoma cell lines. Our data indicate that LMP2A increases ATP generation in multiple Burkitt lymphoma cell lines that were dependent on HIF-1α. Subsequent studies indicate that the addition of the mTOR inhibitor, rapamycin, blocked the LMP2A-dependent increase in HIF-1α. Further studies demonstrate that LMP2A does not increase HIF-1α levels by increasing HIF-1α RNA or STAT3 activation. In contrast, LMP2A and mTOR-dependent increase in HIF-1α required mTOR-dependent phosphorylation of p70 S6 Kinase and 4E-BP1. These findings implicate the importance of LMP2A in promoting B cell lymphoma survival by increasing ATP generation and identifying potential pharmaceutical targets to treat EBV-associated tumors. [ABSTRACT FROM AUTHOR]

Background: Burkitt's lymphoma, one of the most common subtypes of pediatric malignant lymphoma, is notorious for its swift onset, aggressive proliferation, pronounced invasiveness, and marked malignancy. The therapeutic landscape for Burkitt's lymphoma currently falls short of providing universally effective and tolerable solutions. Andrographolide, a primary active component of Andrographis paniculata, is renowned for its properties of heat-clearing, detoxification, inflammation reduction, and pain relief. It is predominantly used in treating bacterial and viral infections of the upper respiratory tract, as well as dysentery. Various reports highlight the antitumor effects of andrographolide. Yet, its specific impact and the underlying mechanism of action on Burkitt's lymphoma remain an uncharted area of research. Method: We employed network pharmacology to pinpoint the targets of andrographolide's action on Burkitt's lymphoma and the associated pathways. We then evaluated the impact of andrographolide on Burkitt's lymphoma using both in vitro and in vivo patient-derived xenograft (PDX) models. Concurrently, we confirmed the molecular targets of andrographolide in Burkitt's lymphoma through immunofluorescence assays. Result: Utilizing network pharmacology, we identified 15 relevant targets, 60 interrelationships between these targets, and numerous associated signaling pathways for andrographolide's action on Burkitt's lymphoma. In vitro efficacy tests using High-throughput Drug Sensitivity Testing and in vivo PDX model evaluations revealed that andrographolide effectively curtailed the growth of Burkitt's lymphoma. Moreover, we observed a increased in the expression of JUN (c-Jun) and CASP3 (Caspase 3) proteins in Burkitt's lymphoma cells treated with andrographolide. Conclusion: Andrographolide inhibits the growth of Burkitt's lymphoma by inhibiting JUN and CASP3 proteins. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Immunology. It discusses the role of Epstein-Barr virus (EBV) in inducing T cell immunity in cancers. The editorial highlights the complexity of the immune response to EBV and its significance in cancer progression and management. It also explores the potential of EBV-specific T cell responses for therapeutic purposes, including targeting EBV-associated malignancies and redirecting T cell activity to EBV-unrelated cancers. The document emphasizes the need for further research to fully understand the role of EBV-induced TAA-specific T cells in cancers not traditionally linked to the virus. [Extracted from the article]

Burkitt lymphoma is a highly aggressive B-cell non-Hodgkin lymphoma characterized by rapid growth, and Burkitt lymphoma originating in the tonsil is rare. Most of the cases have no obvious specific symptoms in the early stage, and the clinical symptoms are varied. Children’s symptoms are more atypical, which are easy to be misdiagnosed and missed. We report a case of adolescent with unilateral tonsil enlargement in our hospital, who was diagnosed with Burkitt lymphoma (BL). For patients with rapid enlargement of the tonsils in a short period, asymmetry of the tonsils (Brodskyscale tonsil size difference ≥ 2 degrees), mainly local symptoms but without obvious systemic symptoms, and rare enlarged lymph nodes in the neck, and no obvious abnormalities in laboratory tests, CT or MRI examination of the neck, or further PET/CT examination should be completed in time. When suspected malignant tumors revealed on imaging, especially high value of SUVmax on PET/CT, tonsil biopsy should be performed. Early detection. Early diagnosis can improve the prognosis of Burkitt lymphoma. In this case, the diagnosis was timely and accurate. Surgical resection of the left tonsil alleviated local symptoms in this cas, and chemotherapy treatment was timely completed after postoperative pathology. Efficacy of surgery combined with chemotherapy is good for the patient and long-term follow-up is available.

Ovarian tissue cryopreservation (OTC) and subsequent transplantation (OTT) is a fertility preservation technique widely offered to prepubertal girls and young fertile women who need to undergo oncological treatment but are at a high risk of infertility. However, OTT is not considered safe in patients with certain diseases like leukemia, Burkitt's lymphoma, and ovarian cancer because of the associated risk of malignant cell reintroduction. In vitro follicle development has therefore emerged as a promising means of obtaining mature metaphase II (MII) oocytes from the primordial follicle (PMF) pool contained within cryopreserved ovarian tissue, without the need for transplantation. Despite its significant potential, this novel approach remains highly challenging, as it requires replication of the intricate process of intraovarian folliculogenesis. Recent advances in multi-step in vitro culture (IVC) systems, tailored to the specific needs of each follicle stage, have demonstrated the feasibility of generating mature oocytes (MII) from early-stage human follicles. While significant progress has been made, there is still room for improvement in terms of efficiency and productivity, and a long way to go before this IVC approach can be implemented in a clinical setting. This comprehensive review outlines the most significant improvements in recent years, current limitations, and future optimization strategies. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) contributes to the development of a significant subset of human lymphomas. As a herpes virus, EBV can transition between a lytic state which is required to establish infection and a latent state where a limited number of viral antigens are expressed which allows infected cells to escape immune surveillance. Three broad latency programs have been described which are defined by the expression of viral proteins RNA, with latency I being the most restrictive expressing only EBV nuclear antigen 1 (EBNA1) and EBV-encoded small RNAs (EBERs) and latency III expressing the full panel of latent viral genes including the latent membrane proteins 1 and 2 (LMP1/2), and EBNA 2, 3, and leader protein (LP) which induce a robust T-cell response. The therapeutic use of EBV-specific T-cells has advanced the treatment of EBV-associated lymphoma, however this approach is only effective against EBV-associated lymphomas that express the latency II or III program. Latency I tumors such as Burkitt lymphoma (BL) and a subset of diffuse large B-cell lymphomas (DLBCL) evade the host immune response to EBV and are resistant to EBV-specific T-cell therapies. Thus, strategies for inducing a switch from the latency I to the latency II or III program in EBV+ tumors are being investigated as mechanisms to sensitize tumors to Tcell mediated killing. Here, we review what is known about the establishment and regulation of latency in EBV infected B-cells, the role of EBV-specific T-cells in lymphoma, and strategies to convert latency I tumors to latency II/III. [ABSTRACT FROM AUTHOR]

The current chemotherapy treatments have led to an improvement in survival rates for pediatric Burkitt's lymphoma (BL). Survival in children with high-grade, mature B-cell non-Hodgkin's lymphoma (B-NHL) has been prolonged by six rituximab doses combined with chemotherapy, whereas the efficacy of four doses has not been reported. This study aimed to explore optimal therapeutic strategies—the number of doses of rituximab based on different risk groups—and also aim to investigate the clinical characteristics of Chinese pediatric BL. This study consecutively enrolled children with BL in Beijing Children's Hospital who received French-American-British mature B-cell lymphoma 96 (FAB/LMB96). The patients were divided into three groups: R0 group (chemotherapy alone), R6 group (chemotherapy combined with six rituximab doses), and R4 group (chemotherapy combined with four rituximab doses). The clinical characteristics and outcomes were evaluated. Univariate and multivariate analyses and prognostic nomogram were used to assess prognostic factors. A nomogram was developed that predicted overall survival based on the Cox proportional hazards model, and the concordance index (C-index) and a calibration curve were used to determine its predictive and discriminatory capacity. We enrolled 385 boys and 71 girls, with a median age of 6 years (1–14 years). Of these, 296 patients (65%) had initial abdominal symptoms, 182 (40%) had bulky disease, 46 (10%) had B symptoms, 77 (16.9%) had BL-ALL (blasts ≥ 25% in bone marrow (BM)), 96 (21%) had central nervous system (CNS) disease, 406 (89%) were in stages III–IV, 378 (83%) were in group C, 170 (37.2%) had lactate dehydrogenase (LDH) levels ≥ 1000 U/L at initial diagnosis, and 137 (30%) had tumor lysis syndrome. The R0, R6, and R4 groups included 79, 144, and 227 patients, respectively. Six patients were excluded due to treatment withdrawal for various reasons. The 3-year overall survival (OS) and event-free survival (EFS) percentages were 92% ± 1.3% and 91.3% ± 1.3%, respectively, in all cohorts, whereas the 3-year EFS percentage was 83.5% ± 4.2%, 93% ± 2.1%, and 92.9% ± 1.8% in the R0, R6, and R4 groups, respectively (P = 0.025). The nomogram included four important variables based on a multivariate analysis of the primary cohort: course of disease ≤ 20 days, presence of bulky disease at the beginning of diagnosis, central nervous system(CNS) invasion, and dosage of rituximab. The calibration curve showed that the nomogram was able to predict 3-year OS accurately. The C-index of the nomogram for OS prediction was 0.79 for both cohorts. In our hospital, pediatric BL was more commonly observed in school-age boys with an abdominal mass and mostly in advanced stages at initial diagnosis. The FAB/LMB96 regimen combined with rituximab significantly increased survival outcomes. We observed no significant differences between four and six doses of rituximab in terms of treatment outcomes. The proposed nomogram provides an individualized risk estimate of OS in patients with BL and may assist treatment decision-making or rituximab dose design. [ABSTRACT FROM AUTHOR]

Introduction Burkitt's lymphoma (BL) is a highly aggressive B cell non-Hodgkin lymphoma (NHL) having three distinct subtypes: endemic, sporadic, and immunodeficiency-associated BL. Sporadic BL accounts for only 1 to 2% of adult NHL. Objectives The objective of this article was to study the clinical profile and treatment outcome of patients with BL. Materials and Methods This was a retrospective study of 60 patients with BL conducted in the department of medical oncology at a tertiary cancer center in India during a 10-year period. Patients with BL/leukemia above 14 years of age diagnosed during the study period were included and their clinical presentation, treatment details, and outcome were studied. Results Among 60 cases with BL, there were 41 males and 19 females. The median age at presentation was 42 years (range: 14–81 years). The main symptoms were lymphadenopathy, abdominal pain, and abdominal distension. Two patients each had paraparesis, breast lump, and jaw swelling and one patient had involvement of the cervix. Thirteen patients had features of tumor lysis at presentation. The Ann Arbor stage was I in 17, II in 16, III in 5, and IV in 22. Fifty-five patients received combination chemotherapy that included hyper-cyclophosphamide, vincristine, adriamycin, dexamethasone ± rituximab (hyper-CVAD ± R; 35), cyclophosphamide, adriamycin, vincristine, prednisolone/ cyclophosphamide, vincristine, prednisolone ± rituximab CHOP ± R (13), Berlin-Frankfurt-Munich protocol (4), and others (3). Thirty-four patients attained remission, 13 patients had progressive disease, and 8 patients died during chemotherapy. At a median follow-up of 113 months, 58% patients were alive. Conclusions BL accounts for 1.57% of NHL above the age of 14 years with male preponderance. Intensive, short-duration chemotherapy is the standard treatment. Treatment with hyper-CVAD ± R gives 8-year progression-free survival and overall survival (OS) of 60%. Treatment with CHOP ± R is an alternative option in elderly frail patients with an 8-year OS of 46%. [ABSTRACT FROM AUTHOR]

Objectives Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare group of neoplasms that share features of eosinophilia and lineage promiscuity. First, we described a challenging case of acute leukemia with lineage switch and cytogenetically cryptic FGFR1. Second, we aimed to systemically review this phenomenon in published literature. Methods A 68-year-old man with a history of chemotherapy exposure presented with acute leukemia of myeloid lineage without eosinophilia or 8p11 abnormalities on karyotyping. Over a refractory and relapsing course, the blast phenotype shifted to B lymphoid. Results Fluorescence in situ hybridization identified a cytogenetically cryptic FGFR1 rearrangement, likely a paracentric inversion. We identified 26 published cases of FGFR1 -rearranged acute leukemia with ambiguous, mixed, or switching lineage. Although there was variability in the partner gene, anatomical location of different phenotypes, and timing of lineage switch, the prognosis was consistently poor in the absence of novel therapy. Conclusions Ours is the only reported case of FGFR1 -rearranged neoplasms with a disease sequence of acute myeloid leukemia transforming to B-cell acute lymphoblastic leukemia and 1 of only 3 reported cases with cytogenetically cryptic FGFR1 rearrangement. Fluorescence in situ hybridization testing for FGFR1 rearrangement should be a standard investigation in leukemia of mixed or switching lineage. [ABSTRACT FROM AUTHOR]

Burkitt Lymphoma, an aggressive form of non-Hodgkin's lymphoma, is a rare cause of ileocolic intussusception in adult patients. We present the case of a 17-year-old male patient, with a history of non-Hodgkin's lymphoma in childhood, presenting with acute abdominal pain, vomiting, and diarrhea. CT and colonoscopy findings revealed ileocolic intussusception with a large ileocecal mass, leading to a diagnosis of Burkitt Lymphoma after histopathological and immunohistochemical examination. This case highlights the rarity of Burkitt Lymphoma causing intussusception in adults, a condition more commonly seen in children. The case also underscores the importance of considering Burkitt Lymphoma in patients with a history of non-Hodgkin's lymphoma presenting with acute abdominal symptoms. He was successfully treated with surgery without any complications. On follow-ups, he is doing well. [ABSTRACT FROM AUTHOR]

Objectives: Dominant‐activating (DA) lesions in RAC2 have been reported in 18 individuals to date. Some have required haematopoietic stem cell transplantation (HSCT) for their (severe) combined immunodeficiency syndrome phenotype. We aimed to investigate clinical and cellular features of a kindred harbouring a novel variant in RAC2 p.Ile21Ser (I21S) to better understand DA lesions' phenotypic spectrum. Methods: Clinical and immunological information was collated for seven living individuals from the same kindred with RAC2 p.I21S. We evaluated neutrophil morphology, RAC2 protein expression and superoxide production using freshly isolated neutrophils stimulated with phorbol‐12‐myristate‐13‐acetate (PMA) and N‐formyl‐MetLeuPhe (fMLP). Results: Patient 1 (P1, aged 11, male) has a history of bacterial suppurative otitis media, viral and bacterial cutaneous infections. P1's siblings (P2, P3), mother (P4), maternal aunt (P5) and uncle (P6) have similar infection histories. P1's maternal cousin (P7) presented with Burkitt's lymphoma at age 9. All affected individuals are alive and none has required HSCT to date. They have chronic lymphopenia affecting the CD4+T and B‐cell compartments. P1–3 have isolated reduction in IgM levels whereas the adults universally have normal immunoglobulins. Specific antibody responses are preserved. Affected individuals have neutrophil vacuolation, and their neutrophils have enhanced superoxide production compared to healthy controls. Conclusion: RAC2 p.I21S is an activating variant causing notable morphological and functional abnormalities similar to other reported DA mutations. This novel variant expands the broad clinical phenotypic spectrum of RAC2 DA lesions, emphasising the need to tailor clinical management according to patients' disease phenotype and severity. [ABSTRACT FROM AUTHOR]

AbstractCancer research has extensively explored various factors contributing to cancer development, including chemicals, drugs, smoking, and obesity. However, the role of bacterial infections in cancer induction remains underexplored. In particular, the mechanisms underlying H. pylori-induced B-cell lymphoma, a potential consequence of bacterial infection, have received little attention. In recent years, there has been speculation about contagious agents causing persistent inflammation and encouraging B-lymphocyte transition along with lymphomagenesis. MALT lymphoma associated with chronic H. pylori infection, apart from two other central associated lymphomas - Burkitt’s Lymphoma and DLBCL, is well studied. Owing to the increasing colonization of H. pylori in the host gut and its possible action in the development of B-cell lymphoma, this review aims to summarize the existing reports on different B-cell lymphomas’ probable association with H. pylori infections; also emphasizing the function of the organism in lymphomagenesis; including its interaction with the host, pathogen and host-specific factors, and tumor microenvironment. [ABSTRACT FROM AUTHOR]

Burkitt lymphoma is a highly invasive non-Hodgkin lymphoma. Sporadic Burkitt's lymphoma is commonly found in the abdomen. However, Burkitt lymphoma infiltrating the uterus is uncommon in occurrence. We report the results of 18F-FDG PET/CT examination of a 36-year-old woman. The report indicates that in addition to the strong uptake of FDG imaging agent in the uterus, bilateral cervical and abdominal lymph nodes also have strong activity. At the same time, it was also found that bilateral small breast nodules, sacral canal and multiple bones in the whole body showed a radiation uptake pattern similar to that of the uterus. 18F-FDG PET/CT imaging can help determine the extent of the disease and the affected body area, which is helpful to guide the treatment decision. This case report shows the application of 18F-FDG PET/CT imaging in the diagnosis, staging and post-treatment evaluation of Burkitt lymphoma of the uterus. It provides very useful information for clinicians and helps to improve the accuracy of diagnosis and treatment effect. [ABSTRACT FROM AUTHOR]

Key Clinical Message This report highlights the risk of latent tuberculosis (TB) reactivation after treatment with Polatuzumab Vedotin (PV), Rituximab, and Bendamustine (PBR protocol) despite appropriate chemoprophylaxis. A 48‐year‐old male with refractory Burkitt's lymphoma (BKL) was treated with PBR protocol. At baseline, the patient had a negative QuantiFERON test result, which turned out to be positive prior to starting PBR. He received chemoprophylaxis for 9 months and was compliant with treatment. One year later, he was admitted with COVID‐19 pneumonia and was treated according to the protocol. His symptoms persisted for 1 month. Investigations yielded disseminated TB‐infiltrated bone marrow and pleura. Downstream B‐cell and T‐cell depletion secondary to CD20 and CD79b antagonism may potentially explain the increased risk of TB reactivation associated with the combination of PV and rituximab. Further research is necessary to monitor the risk of TB reactivation among patients receiving a combination of PV and rituximab, especially in endemic areas with high prevalence and incidence of TB.

Chronic lymphocytic leukaemia (CLL) is a malignancy of the immune B lymphocyte cells and is the most common leukaemia diagnosed in developed countries. In this paper, we report the synthesis and antiproliferative effects of a series of (E)-9-(2-nitrovinyl)anthracenes and related nitrostyrene compounds in CLL cell lines and also in Burkitt's lymphoma (BL) cell lines, a rare form of non-Hodgkin's immune B-cell lymphoma. The nitrostyrene scaffold was identified as a lead structure for the development of effective compounds targeting BL and CLL. The series of structurally diverse nitrostyrenes was synthesised via Henry–Knoevenagel condensation reactions. Single-crystal X-ray analysis confirmed the structure of (E)-9-chloro-10-(2-nitrobut-1-en-1-yl)anthracene (19f) and the related 4-(anthracen-9-yl)-1H-1,2,3-triazole (30a). The (E)-9-(2-nitrovinyl)anthracenes 19a, 19g and 19i–19m were found to elicit potent antiproliferative effects in both BL cell lines EBV−MUTU-1 (chemosensitive) and EBV+ DG-75 (chemoresistant) with >90% inhibition at 10 μM. Selected (E)-9-(2-nitrovinyl)anthracenes demonstrated potent antiproliferative activity in CLL cell lines, with IC50 values of 0.17 μM (HG-3) and 1.3 μM (PGA-1) for compound 19g. The pro-apoptotic effects of the most potent compounds 19a, 19g, 19i, 19l and 19m were demonstrated in both CLL cell lines HG-3 and PGA-1. The (E)-nitrostyrene and (E)-9-(2-nitrovinyl)anthracene series of compounds offer potential for further development as novel chemotherapeutics for CLL. [ABSTRACT FROM AUTHOR]

Simple Summary: Epstein Barr virus (EBV) is a constant companion of humans with more than 95% of the adult population being persistently infected. Fortunately, this companionship is mostly asymptomatic, but in around 300,000 new patients every year, EBV-associated cancers emerge. These medical cases are mostly caused by environmental or genetic conditions that either increase EBV-associated tumorigenesis or weaken its immune control. In this review, I will discuss co-infections as important environmental risk factors for EBV-associated malignancies and how both EBV infection but also the respective co-infections could be targeted to reduce the associated disease load. The oncogenic and persistent Epstein Barr virus (EBV) is carried by more than 95% of the human adult population. While asymptomatic in most of these, EBV can cause a wide variety of malignancies of lymphoid or epithelial cell origin. Some of these are also associated with co-infections that either increase EBV-induced tumorigenesis or weaken its immune control. The respective pathogens include Kaposi-sarcoma-associated herpesvirus (KSHV), Plasmodium falciparum and human immunodeficiency virus (HIV). In this review, I will discuss the respective tumor entities and possible mechanisms by which co-infections increase the EBV-associated cancer burden. A better understanding of the underlying mechanisms could allow us to identify crucial features of EBV-associated malignancies and defects in their immune control. These could then be explored to develop therapies against the respective cancers by targeting EBV and/or the respective co-infections with pathogen-specific therapies or vaccinations. [ABSTRACT FROM AUTHOR]

Background: Dexamethasone (DEX) induces CYP3A activity in a concentration-dependent manner. However, no study has examined changes in the blood concentration of CYP3A substrate drugs when DEX is administered at high doses. Herein, we present a case in which tacrolimus (TAC), a typical CYP3A substrate drug, was co-administered with a chemotherapy regimen that included high-dose DEX. Case presentation: A 71-year-old woman underwent liver transplantation for hepatocellular carcinoma 18 years prior to her inclusion in this case study. She was receiving TAC orally at 2 mg/day and had a stable trough blood concentration of approximately 4 ng/mL and a trough blood concentration/dose (C/D) ratio of approximately 2. The patient was diagnosed with post-transplant lymphoproliferative disease (histological type: Burkitt's lymphoma) after admission. Thereafter, the patient received cyclophosphamide-prednisolone (CP), followed by two courses of R-HyperCVAD (rituximab, cyclophosphamide, doxorubicin, vincristine, and DEX) and R-MA (rituximab, methotrexate, and cytarabine) replacement therapy. DEX (33 mg/day) was administered intravenously on days 1–4 and days 11–14 of R-HyperCVAD treatment, and aprepitant (APR) was administered on days 1–5 in both courses. The TAC C/D ratio decreased to approximately 1 on day 11 during both courses, and then increased. Furthermore, a decreasing trend in the TAC C/D ratio was observed after R-MA therapy. The decrease in the TAC C/D ratio was attributed to APR administration rather than to DEX. Conclusion: The induction of CYP3A activity by a high dose of DEX may not be strong. The pharmacokinetic information on DEX and in vitro enzyme activity induction studies also suggested that CYP3A activity induction is not prominent under high-dose DEX treatment. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T-cells (CAR-T) are now a standard approach for treating relapsed/refractory B-cell lymphomas. Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) is a newly described entity that can manifest following CAR-T. Bone marrow (BM) aplasia is an uncommon manifestation of IEC-HS reported after CAR-T-cell therapy and is defined as the reduction or absence of hematopoietic progenitor cells resulting in severe pancytopenia. We describe the case of a 44-year-old female with relapsed/refractory Burkitt lymphoma (BL) who received treatment with lisocabtagene maraleucel with her post-CAR-T course complicated by cytokine release syndrome (CRS) and IEC-HS ultimately leading to persistent BM aplasia. She underwent a rescue allogeneic stem cell transplant but ultimately succumbed to progressive disease. IEC-HS is an increasingly recognized complication that occurs after CAR-T treatments that can result in aplasia, a dangerous complication with serious sequelae including infection, transfusion dependence, and high risk for hemorrhage. The underlying mechanism is poorly understood, and further studies are needed to understand how to treat it better. [ABSTRACT FROM AUTHOR]

TL-895 (formerly known as M7583) is a potent, highly selective, adenosine triphosphate (ATP)-competitive, second-generation, irreversible inhibitor of Bruton's tyrosine kinase (BTK). We characterized its biochemical and cellular effects in in vitro and in vivo models. TL-895 was evaluated preclinically for potency against BTK using IC50 concentration–response curves; selectivity using a 270-kinase panel; BTK phosphorylation in Ramos Burkitt's lymphoma cells by ProteinSimple Wes analysis of one study; anti-proliferative effects in primary chronic lymphocytic leukemia (CLL) blasts; cell viability effects in diffuse large B-cell lymphoma (DLBCL) and mantle-cell lymphoma (MCL) cell lines; effects on antibody-dependent cell-mediated cytotoxicity (ADCC) from Daudi cells and chromium-51 release from human tumor cell lines; and efficacy in vivo using four MCL xenograft model and 21 DLBCL patient-derived xenograft (PDX) models (subtypes: 9 ABC, 11 GCB, 1 Unclassified). TL-895 was active against recombinant BTK (average IC50 1.5 nM) and inhibited only three additional kinases with IC50 within tenfold of BTK activity. TL-895 inhibited BTK auto-phosphorylation at the Y223 phosphorylation site (IC50 1–10 nM). TL-895 inhibited the proliferation of primary CLL blasts in vitro and inhibited growth in a subset of activated DLBCL and MCL cell lines. TL-895 inhibited the ADCC mechanism of therapeutic antibodies only at supra-clinical exposure levels. TL-895 significantly inhibited tumor growth in the Mino MCL xenograft model and in 5/21 DLBCL PDX models relative to vehicle controls. These findings demonstrate the potency of TL-895 for BTK and its efficacy in models of B-cell lymphoma despite its refined selectivity. [ABSTRACT FROM AUTHOR]

Background: A significant level of CD70 can be detected in various types of tumor tissues and CD27 is expressed on Treg cells, but CD70 expression is low in normal tissues. The interaction between CD70 and CD27 can stimulate the proliferation and survival of cancer cells and increase the level of soluble CD27, which is associated with poor prognosis in patients with lymphoma and certain solid tumors. Thus, it is a promising therapeutic target for the treatment of many major CD70+ cancer indications, including CD70+ lymphoma, RCC, NSCLC, HNSCC and OC. Methods: IMM40H was obtained through hybridoma screening and antibody humanization techniques. IMM40H was evaluated for its binding, blocking, Fcdependent effector functions and antitumor activity characteristics in various in vitro and in vivo systems. The safety and tolerability profile of IMM40H were evaluated through single and repeated administration in cynomolgus monkeys. Results: In vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively. IMM40H also exhibited potent Fc-dependent effector functions (ADCC/CDC/ADCP), and could make a strong immune attack on tumor cells and enhance therapeutic efficacy. Preclinical findings showed that IMM40H had potent antitumor activity in multiple myeloma U266B1 xenograft model, and could eradicate subcutaneously established tumors at a low dose of 0.3 mg/kg. IMM40H (0.3 mg/kg) showed therapeutic effects faster than cusatuzumab (1 mg/kg). A strong synergistic effect between IMM01 (SIRPa-Fc fusion protein) and IMM40H was recorded in Burkitt’s lymphoma Raji and renal carcinoma cell A498 tumor models. In cynomolgus monkeys, the highest nonseverely toxic dose (HNSTD) for repeat-dose toxicity was up to 30 mg/kg, while the maximum tolerated dose (MTD) for single-dose toxicity was up to 100 mg/kg, confirming that IMM40H had a good safety and tolerability profile. Conclusion: IMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling. [ABSTRACT FROM AUTHOR]

Extraganglionic Burkitt's lymphoma is rare. Primary thyroid localization accounts for 1% to 5% of malignant tumors of the thyroid gland. The association of Burkitt's lymphoma and pregnancy is even rarer. Our patient was pregnant at 36 weeks. She was brought to the emergency department with anterior cervical swelling, rapidly increasing in volume and becoming compressive for 15 days, in addition to dysphonia and inspiratory dyspnea. Cervical ultrasound and computed tomography scan revealed a compressive and plunging goiter. Surgery attempted after fetal extraction proved impossible due to massive tumor infiltration into adjacent structures shielding the cervical region. Accordingly, the act was limited to a glandular biopsy. The newborn was healthy. Histological examination confirmed the diagnosis of Burkitt's lymphoma. Given the poor general condition of the patient, chemotherapy was not administered and the patient died after 15 days of stay in intensive care unit. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Burkitt's lymphoma is a highly aggressive non‐Hodgkin's lymphoma that can affect various parts of the body, which include jaw, facial bones, retroperitoneum, and abdominal viscera, it is worth noting that breast involvement is extremely rare in Burkitt's lymphoma and has not been documented. Burkitt's lymphoma is a highly aggressive non‐Hodgkin's lymphoma that can affect various parts of the body including breast. This sarcoma is identified as a rapidly fatal malignant lymphoma syndrome and 50% of all malignant tumors in children. However, breast involvement has not been documented. A 19‐year‐old male presented to our emergency department with a left breast swelling for 2 months associated with drenching night sweats, weight loss and evening fevers. Physical examination revealed a mass measuring approximately 15 × 16 × 15 cm in the widest dimension, skin hyperpigmentation, no nipple discolorations, discharges, and non‐tender on palpation. Biopsy was done, and the histology report revealed sheets of monomorphic medium lymphocytes with a high mitotic rate and frequent apoptotic bodies showing a starry‐sky appearance. The immunohistochemistry report revealed positive staining for Ki‐67, CD‐20, and CD‐10 tumor markers and CD45 on flow cytometry. The patient was started on aggressive hydration, rasubricase administration, CODOX‐M/IVAC regimen 6 cycles, and G‐CSF and registered significant reduction in the size of the mass. Burkitt's lymphoma is a highly aggressive non‐Hodgkin's lymphoma that can affect various parts of the body. It commonly involves the jaw, facial bones, retroperitoneum, and abdominal viscera. The disease typically affects young patients in areas of high incidence, such as the jaw, whereas visceral involvement is more common in older patients in low‐incidence areas. It is worth noting that breast involvement is extremely rare in Burkitt's lymphoma. [ABSTRACT FROM AUTHOR]

Background: As a new point, some very rare features can be revealed as initial diagnosis of acute lymphoblastic leukemia (ALL) without any evidence of lymphoma-like behavior which after initial recovery, presents with new evidence of lymphoma. Herein, a case of the immunophenotypes of blast cells in B-cell precursor acute lymphoblastic leukemia originated from MYC gene-related that was evidenced later by burkitt lymphoma feature. Case Presentation: Our case was initially diagnosed as a typical B-cell ALL cells with L1 morphology in peripheral blood smear and bone marrow aspiration that was not recovered and referred again that was finally featured as burkitt's lymphoma with L3 morphological feature. Conclusion: Thus, in the primary diagnosis of B-cell ALL and especially in cases with treatment failure, the final feature of burkitt's lymphoma should be potentially in mind. [ABSTRACT FROM AUTHOR]

IntroductionPatients with systemic lupus erythematosus (SLE) are at a higher risk of developing cancer, particularly hematological malignancies such as lymphoma and leukemia. However, existing studies on this topic that assess cancer incidence following SLE diagnosis are limited. In addition, SLE can be diagnosed after cancer, although such cases in children have been rarely reported.Case reportWe present the case of a 2.6-year-old boy who presented to our institute with fever and abdominal pain. His physical examination revealed a periumbilical mass, which was pathologically diagnosed as Burkitt's lymphoma. Autologous stem cell transplantation was performed to consolidate the effect of chemotherapy and reduce the risk of cancer relapse. He was diagnosed with SLE 5 years later, following the presentation of a fever with rash, positive autoantibodies, decreased complement, and kidney involvement. At the final follow-up, the patient was still alive and showed no recurrence of Burkitt's lymphoma or disease activity of SLE.ConclusionDespite the low frequency of SLE in children with lymphoma, cancer and SLE may be induced by a common mechanism involving B-cell cloning and proliferation. Therefore, hematologists and rheumatologists should be aware of the occurrence of these two conditions during patient follow-up.

Non-Hodgkin’s lymphoma (NHL) accounts for 60% of childhood lymphomas and is the fourth most common childhood malignancy. Burkitt’s lymphoma (BL) accounts for 40% of NHLs. Burkitt’s lymphoma is mostly of abdominal origin and has the highest cell count doubling rate. Tuberculosis (TB) is one of the chronic diseases caused by the Mycobacterium tuberculosis bacillus, which has high morbidity and mortality and occurs most frequently in the lung. In this case report, we present a patient with a previous diagnosis of BL who developed pleural effusion while under rituximab-ifosfamide carboplatin etoposide treatment, and TB polymerase chain reaction (PCR) was revealed to be positive in the TB PCR screening test of the pleural fluid. To our knowledge, there is no previous study of the coexistence of BL and TB pleurisy in the literature. When pleural effusion develops in patients with BL under chemotherapy treatment, it should be kept in mind that TB may be present, and anti-TB treatment should be started as soon as the diagnosis is made. There is limited information in the literature about the frequency of tuberculous pleurisy in patients with BL.

Enhancer of zeste homolog 2 (EZH2) and Bruton's tyrosine kinase (BTK) are both key factors involved in the development and progression of hematological malignancies. Clinical studies have demonstrated the potential of various EZH2 inhibitors, which target the methyltransferase activity of EZH2, for the treatment of lymphomas. However, despite their ability to effectively reduce the H3K27me3 levels, these inhibitors have shown limited efficacy in blocking the proliferation of lymphoma cells. To overcome this challenge, we employed a hydrophobic tagging approach utilizing MS1943, a selective EZH2 degrader. In this study, we investigated the inhibitory effects of two drugs, the FDA-approved EZH2 inhibitor Tazemetostat, currently undergoing clinical trials, and the novel drug MS1943, on Burkitt's lymphoma. Furthermore, we assessed the potential synergistic effect of combining these drugs with the BTK inhibitor Ibrutinib. In this study, we evaluated the effects of combination therapy with MS1943 and Ibrutinib on the proliferation of three Burkitt's lymphoma cell lines, namely RPMI1788, Ramos, and Daudi cells. Our results demonstrated that the combination of MS1943 and Ibrutinib significantly suppressed cell proliferation to a greater extent compared to the combination of Tazemetostat and Ibrutinib. Additionally, we investigated the underlying mechanisms of action and found that the combination therapy of MS1943 and Ibrutinib led to the upregulation of miR29B-mediated p53- upregulated modulator of apoptosis PUMA, BAX, cleaved PARP, and cleaved caspase-3 in Burkitt's lymphoma cells. These findings highlight the potential of this innovative therapeutic strategy as an alternative to traditional EZH2 inhibitors, offering promising prospects for improving treatment outcomes in Burkitt's lymphoma. [ABSTRACT FROM AUTHOR]

Introduction: Artesunate, a derivative of artemisinin, has anti-malarial effects, and in recent years has also been reported to have anti-tumor activity. However, its anti-tumor mechanisms are not well understood. Methods: In this study, we focused on the targeting of Hsp90 by artesunate to inhibit tumor cell proliferation, whichwe examined using immunoprecipitation, a proliferation assay, flow cytometry, western blotting, a tumor xenograft animal model, and immunohistochemistry. Furthermore, to examine the tumor-suppressive effects of artesunatein nude mice, we used artesunate-loaded PLGA-PEG nanoparticles. Results: The binding of artesunate to Hsp90 was found to reduce the expression of its client proteins AKT, ERK, p-AKT, p-ERK, and EGFR, thereby blocking the cell cycle at the G0/G1 → S stage in lymphoma cells and inducing apoptosis. In addition, the results of tumor xenograft experiments revealed that artesunate reduced the expression of AKT and ERK proteins in tumor tissues, inhibited tumor proliferation, and reduced tumor size and weight. Furthermore, nanoparticle encapsulation was demonstrated to enhance the anti-cancer activity of artesunate. Discussion: We thus established that artesunate inhibits the proliferation of lymphoma cells by targeting the Hsp90 protein, and we accordingly believe that this compound has potential for development as a novelanti-tumor drug. [ABSTRACT FROM AUTHOR]