Displaying publications 221 - 240 of 373 in total

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  1. TI TS
    Med J Malaya, 1962 Mar;16:214-8.
    PMID: 13921142
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  2. Hafiza, A., Azma, R.Z., Azura, A.H., Azlin, I., Zarina, A.L., Hamidah, N.H.
    Medicine & Health, 2011;6(2):131-138.
    MyJurnal
    Leukaemic stem cells have heterogenous differentiation potential. The immunophenotypes of blast cells are usually consistent throughout the disease course even at relapse. Rarely, blast cells may undergo a ‘lineage switch’ during the course of disease especially during relapse. We would like to highlight such a case in a 10- year old boy who presented with a two weeks history of lethargy, poor appetite, low grade fever, respiratory distress, cardiac failure, generalized oedema and hepatosplenomegaly. Full blood count showed a leucocyte count of 41.5x10 9 /L and platelet count of 37x10 9 /L. The peripheral blood film showed presence of numerous blast cells. Bone marrow aspiration revealed a hypercellular marrow, which consisted of mainly blast cells with high nuclear to cytoplasmic ratio and inconspicuous nucleoli. Immunophenotyping and cytochemistry results were consistent with the diagnosis of Tcell acute lymphoblastic leukaemia. The patient achieved remission after treatment with UK ALL 97 protocol, regime B chemotherapy. However, he relapsed seven months after the initial diagnosis with 26% blast cells in the bone marrow aspirate. The majority was L1 blast cells admixed with some L2 blast cells. Immunophenotyping was consistent with common precursor B acute lymphoblastic leukaemia. The treatment was changed to a more lineage specific chemotherapy. Nonetheless, the patient never achieved remission and was planned for palliative management. This case illustrated a unique and rare case of rapid lineage switch from T-cell acute lymphoblastic leukaemia to common precursor B-cell acute lymphoblastic leukaemia.
    Matched MeSH terms: Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
  3. Azma, R.Z., Zarina, A.L., Hamidah, A., Cheong, SK, Jamal, R., Hamidah, N.H.
    Medicine & Health, 2010;5(1):22-33.
    MyJurnal
    Residual disease in patients with acute leukaemia indicates unfavorable prognosis. The evaluation of remission using flow cytometry allows a better estimation of minimal residual disease (MRD) after induction chemotherapy in childhood acute lymphoblastic leukaemia (ALL) cases. Patients in morphological marrow remission with presence of blast cells of less than 5%, may still have up to 1010 leukaemic cells. However with flow cytometric analysis, lower levels of the residual leukaemic cells (1 in 104 cells) can be detected and it can be used as a tool to predict relapse. This study compared the presenting clinical and haematological features of children with ALL and their residual disease status determined by flow cytometry. Analysis of their MRD status following remission-induction chemotherapy were done at day-28, week-12 and week-20. The cases were also followed up to five years, to determine their survival status. Their residual disease status by flow cytometric immunophenotyping was also compared with their bone marrow findings morphologically. Thirty-eight cases of precursor B-ALL in pediatric patients from UKM Medical Centre (UKMMC) were analyzed. There was no significant correlation between demographic, clinical and haematological features with MRD status at day-28. However, there was a significant correlation between MRD status by flow cytometry and by morphological marrow examination at week-12. Three cases showed persistent MRD findings until week-20 where two of the cases relapsed and died subsequently. Twenty four patients were still alive after five years of follow up.
    Matched MeSH terms: Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma
  4. Nazima SA, Muhaya M, Kok, HS, Hazlita MI
    MyJurnal
    Ocular inflammation from various causes may have similar clinical presentation thus careful clinical evaluations are mandatory particularly when the disease appear to be resistant to treatment. This paper reports a case of ocular lymphoma which was initially treated as Vogt Koyanagi Harada disease at a different centre. A 65-year-old Sudanese man complained of gradual worsening left eye vision. Careful ocular and slit lamp examination revealed a conjunctival lesion with choroidal infiltration as well as exudative retinal detachment. Computed tomography scan (CT scan) showed left eye axial proptosis, and a homogenous enhancing mass at the posterior coat of the globe. Tissue biopsy of the conjunctival lesion revealed marginal Zone B cell (MALT type), low grade, non-Hodgkin’s lymphoma. AS the ocular signs and symptoms progressed, chemotherapy was initiated. The proptosis, exudative retinal detachment, disc hyperemia and swelling improved after chemotherapy. The post treatment CT scan showed reduction of the posterior ocular coat mass. The possibility of malignant lymphoma should be considered in patients with resistant uveitis despite administration of corticosteroid. Ocular lymphoma is an indolent tumour with good prognosis. Careful ocular examination, adequate imaging studies followed by early surgical biopsy will contribute to early diagnosis.
    Matched MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
  5. Priscilla, D., Hamidin, A., Azhar, M. Z., Noorjan, K. O. N., Salmiah, M. S., Bahariah, K.
    MyJurnal
    Objective: To determine the prevalence of major depressive disorder (MDD) in hematological cancer patients and to investigate MDD with quality of life. Methods: The research, which uses a cross sectional design, has been carried out at Ampang Hospital, Kuala Lumpur. The hospital is a tertiary referral center for cancer cases that include non-Hodgkin lymphoma, acute myelogenous leukemia, acute lymphoblastic leukemia, Hodgkin lymphoma and other hematological cancers. In total, 105 patients with hematological malignancies were included in the study. This study employed the MINI International Neuropsychiatric Interview for diagnosis of MDD, the Patient Health Questionnaire (PHQ-9) for symptom severity of depression and the European Organisation for Research and Treatment of Cancer Quality Of Life questionnaire (EORTC QLQ-C30) to assess the quality of life of the respondents. Result: The response rate was 83.3%. The prevalence of MDD was 24.8% (n=26) with the majority of cases classified as moderately severe depression (38.5%). About 92.3% (n=24) of depressed hematological cancer patients were diagnosed with a current episode of MDD. The depressed patients also had significantly reduced quality of life in physical, role, emotional, cognitive and social domains (p
    Matched MeSH terms: Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma
  6. Abdelrahim LM, Peh SC, Kallarakkal TG
    Malays J Pathol, 2018 Apr;40(1):49-56.
    PMID: 29704384
    INTRODUCTION: Epstein-Barr virus (EBV) might be an aetiological agent involved in the pathogenesis of certain Non-Hodgkin's Lymphomas (NHLs). EBV infection has been diagnosed by serologic testing within the tumour biopsies of patients with NHL. However, the association between EBV and NHL is inconsistent with a preference for certain anatomic sites, histologic subtypes and immunosuppressed patients. The objective of this study was to characterise the B-cell NHLs of the oral cavity and maxillofacial region using histological and immunophenotypical techniques and to determine its association with EBV infection.

    MATERIALS AND METHODS: This was a descriptive cross-sectional study that included 14 cases of B-cell NHLs of the oral cavity and maxillofacial region. The haematopoietic and lymphoid tissue tumours classification of WHO was used to categorize the cases. In-situ hybridisation for EBV-encoded RNA was performed to confirm the EBV infection.

    RESULTS: The average age of the patients included in the study was found to be 48.8 ± 23 years with a higher female to male ratio (1.3:1). Our study suggested that diffuse large B-cell lymphomas (DLBCLs) and Burkitt's lymphomas (BLs) constitute the predominant subtypes of lymphomas affecting the oral cavity and maxillofacial regions.

    CONCLUSION: The findings from our study support the view that at least a relatively smaller proportion of B-cell NHLs that occur in the oral cavity and maxillofacial region do not have a pathogenic association with EBV.

    Matched MeSH terms: Lymphoma, B-Cell/virology*
  7. Kasinathan G
    Ann Med Surg (Lond), 2020 Jan;49:1-4.
    PMID: 31871676 DOI: 10.1016/j.amsu.2019.11.007
    ALK-negative anaplastic large cell lymphoma (ALCL) is a peripheral T-cell lymphoma that usually involves lymph nodes or extranodal sites. Leukemic phase of ALK-negative ALCL is exceedingly rare and often carries a poor prognosis. Androgenic steroids have gained popularity among the young, and at higher doses, it can result in immune dysregulation and may be potentially carcinogenic. Case presentation: A 30-year-old gentleman of Malay ethnicity presented to the hematology department with night fevers, loss of weight and bony pain for the past 6 weeks. He is a gymnasium instructor with a history of chronic usage of intramuscular testosterone enanthate. Physical examination revealed ecchymosis over the left elbow and hepatomegaly. A complete blood count depicted anemia, thrombocytopenia and leucocytosis. An 18-Fluorodeoxyglucose positron emission tomography (18-FDG PET/CT) imaging showed a hypermetabolic anterior mediastinal mass of 6.8 × 7.0 × 6.5 cm with diffuse hypermetabolism in the liver, spleen and axial skeleton. The bone marrow trephine and mediastinal tissue histology were consistent with leukemic ALK-negative ALCL. He was treated with CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone) induction chemotherapy in which he required intensive antibiotic and blood support. He progressed with worsening B symptoms and new diffuse lymphadenopathies suggesting rapid dissemination of the disease. He subsequently succumbed to multiorgan failure with disseminated intravascular coagulopathy at the intensive care unit. Conclusion: Leukemic phase ALK-negative ALCL often carries a complex karyotype and requires early intensive polychemotherapy. Use of anabolic steroids depletes the ability of defending lymphocytes to remove tumour producing cells.
    Matched MeSH terms: Lymphoma, T-Cell, Peripheral; Lymphoma, Large-Cell, Anaplastic
  8. Akkour K, Alhulwah M, Alhalal H, Alqahtani N, Arafah M
    Malays J Pathol, 2021 Aug;43(2):327-331.
    PMID: 34448797
    BACKGROUND: Small bowel volvulus is defined as the torsion of the small intestine, potentially leading to bowel obstruction, gangrene and perforation. It is a rare condition, especially in adults.

    CASE PRESENTATION: A 30-year-old man was retrieved from the jungle with severe weight loss and abdominal symptoms. He succumbed to death despite 22 days of intensive medical treatment. An autopsy revealed a ruptured gangrenous ileal volvulus with peritonitis and subdiaphragmatic abscess. Further laboratory analysis detected systemic Candida tropicalis and intestinal gramnegative bacterial sepsis, systemic Zika virus viremia, leptospirosis complicating rhabdomyolysis and disseminated intravascular coagulopathy, Type I Herpes Simplex virus infection of the tongue and upper gastrointestinal tract. The cause of death was the ruptured ileal volvulus, complicated with upper gastrointestinal bleeding due to Herpes simplex virus esophagitis in a malnourished patient with resolving leptospirosis and underlying Zika virus co-infection.

    CONCLUSION: Rare clinical scenarios of adult-onset intestinal volvulus with concomitant multiple infections precludes clinical diagnosis and early treatment, leading to devastating consequences of clinical outcome. The positive clinical and postmortem correlation is a good learning lesson in many disciplines of medicine and science.

    Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse*
  9. Mohd Ridah LJ, A Talib N, Muhammad N, Hussain FA, Zainuddin N
    Asian Pac J Cancer Prev, 2017 10 26;18(10):2781-2785.
    PMID: 29072413
    Introduction: p16 gene plays an important role in the normal cell cycle regulation. Methylation of p16 has been reported to be one of the epigenetic events contributing to the pathogenesis of diffuse large B-cell lymphoma (DLBCL) which occurring at varying frequency. DLBCL is an aggressive and high-grade malignancy which accounts for approximately 30% of all non-Hodgkin lymphoma cases. However, little is known regarding the epigenetic alterations of p16 gene in DLBCL cases in Malaysia. Therefore, the objective of this study was to examine the status of p16 methylation in DLBCL. Methods: A total of 88 formalin-fixed paraffin-embedded DLBCL tissues retrieved from two hospitals located in the east coast of Malaysia, namely Hospital Tengku Ampuan Afzan (HTAA) Pahang and Hospital Universiti Sains Malaysia (HUSM) Kelantan, were chosen for this study. DNA specimens were isolated and subsequently subjected to bisulfite treatment prior to methylation specific-PCR. Two pairs of primers were used to amplify methylated and unmethylated regions of p16 gene. The PCR products were then separated using agarose gel electrophoresis and visualised under UV illumination. SPSS version 12.0 was utilised to perform all statistical analysis. Result: p16 methylation was detected in 65 of 88 (74%) samples. There was a significant association between p16 methylation status and patients aged >50 years old (p=0.04). Conclusion: Our study demonstrated that methylation of p16 tumor suppressor gene in our DLBCL cases is common and significantly increased among patients aged 50 years and above. Aging is known to be an important risk factor in the development of cancers and we speculate that this might be due to the increased transformation of malignant cells in aging cell population. However, this has yet to be confirmed with further research and correlate the findings with clinicopathological parameters.
    Matched MeSH terms: Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse
  10. Steffi W, Zaliana B, Amreen A, Nasirudin N
    Med J Malaysia, 2017 10;72(5):316-317.
    PMID: 29197891 MyJurnal
    Chronic exudative malodorous fungating wound of four years at the right arm due to diffuse large B cell lymphoma managed with silver dressings. In two months of application with nanocrystalline silver coated dressings, there was significant improvement in wound.
    Matched MeSH terms: Lymphoma, B-Cell/complications
  11. Ariffin H, Chen SP, Wong HL, Yeoh A
    Singapore Med J, 2003 Oct;44(10):517-20.
    PMID: 15024455
    In childhood acute lymphoblastic leukaemia (ALL), cytogenetics play an important role in diagnosis, allocation of treatment and prognosis. Conventional cytogenetic analysis, involving mainly karyotyping in our experience, has not been successful in a large proportion of cases due to inadequate metaphase spreads and poor chromosome morphology. Our aim is to develop a highly sensitive and specific method to screen simultaneously for the four most frequent fusion transcripts resulting from specific chromosomal translocations, namely, both the CML- and ALLtype BCR-ABL transcripts of t(9;22), E2A-PBX1 transcript of t(1;19), the MLL-AF4 transcript of t(4;11) and TEL-AML1 (also termed ETV6-CBFA2) of the cryptic t(12;21). A multiplex reverse transcription polymerase chain reaction protocol (RT-PCR) was developed and tested out on archival bone marrow samples and leukaemia cell lines. In all samples with a known translocation detected by cytogenetic techniques, the same translocation was identified by the multiplex-PCR assay. Multiplex RT-PCR assay is an effective, sensitive, accurate and cost-effective diagnostic tool which can improve our ability to accurately and rapidly risk-stratify patients with childhood ALL.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  12. Chong ASS, Ahmad M, Mohd Harizan NB, Alias H, Iqbal Hussain R, Lateh A, et al.
    Asian Pac J Cancer Prev, 2023 Jun 01;24(6):1923-1929.
    PMID: 37378920 DOI: 10.31557/APJCP.2023.24.6.1923
    OBJECTIVE: The caregivers of children diagnosed with acute lymphoblastic leukaemia (ALL) are believed to experience post-traumatic stress symptoms (PTSS), depression and anxiety. This present study endeavoured to explore the prevalence and predictors of PTSS, depression, and anxiety among the caregivers of children with ALL.

    METHODS: Purposive sampling was used to select the 73 caregivers of children with ALL who participated in this cross-sectional study. The Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were used to measure psychological distress.

    RESULT: There was a low prevalence (11%) of post-traumatic stress disorder (PTSD) among the participants. Although all the criteria for PTSD were not met, a few post-traumatic symptoms remained, suggesting that PTSS was likely present. Most of the participants reported minimal symptoms of depression (79.5%) and anxiety (65.8%). Anxiety, depression, and ethnicity predicted the PTSS scores (R2 = .77, p =.000). Subsequently, depression predicted the PTSS scores (R2 = 0.42, p =0.000). Participants of 'Other' or 'Indigenous' ethnicity had lower PTSS scores and higher anxiety scores (R2 = 0.75, p =0.000) than participants of Malay ethnicity.

    CONCLUSION: The caregivers of children with ALL experience post-traumatic stress symptoms (PTSS), depression, and anxiety. These variables co-exist and may have different trajectories in different ethnic groups. Therefore, healthcare providers should take ethnicity and psychological distress into consideration when providing paediatric oncology treatment and care.

    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  13. Young LS, Yap LF, Murray PG
    Nat Rev Cancer, 2016 12;16(12):789-802.
    PMID: 27687982 DOI: 10.1038/nrc.2016.92
    It is more than 50 years since the Epstein-Barr virus (EBV), the first human tumour virus, was discovered. EBV has subsequently been found to be associated with a diverse range of tumours of both lymphoid and epithelial origin. Progress in the molecular analysis of EBV has revealed fundamental mechanisms of more general relevance to the oncogenic process. This Timeline article highlights key milestones in the 50-year history of EBV and discusses how this virus provides a paradigm for exploiting insights at the molecular level in the diagnosis, treatment and prevention of cancer.
    Matched MeSH terms: Lymphoma/virology
  14. Costas L, Lujan-Barroso L, Benavente Y, Allen NE, Amiano P, Ardanaz E, et al.
    Am J Epidemiol, 2019 Feb 01;188(2):274-281.
    PMID: 30481275 DOI: 10.1093/aje/kwy259
    The role of hormonal factors in the etiology of lymphoid neoplasms remains unclear. Previous studies have yielded conflicting results, have lacked sufficient statistical power to assess many lymphoma subtypes, or have lacked detailed information on relevant exposures. Within the European Prospective Investigation Into Cancer and Nutrition cohort, we analyzed comprehensive data on reproductive factors and exogenous hormone use collected at baseline (1992-2000) among 343,458 women, including data on 1,427 incident cases of B-cell non-Hodgkin lymphoma (NHL) and its major subtypes identified after a mean follow-up period of 14 years (through 2015). We estimated hazard ratios and 95% confidence intervals using multivariable proportional hazards modeling. Overall, we observed no statistically significant associations between parity, age at first birth, breastfeeding, oral contraceptive use, or ever use of postmenopausal hormone therapy and risk of B-cell NHL or its subtypes. Women who had undergone surgical menopause had a 51% higher risk of B-cell NHL (based on 67 cases) than women with natural menopause (hazard ratio = 1.51, 95% confidence interval: 1.17, 1.94). Given that this result may have been due to chance, our results provide little support for the hypothesis that sex hormones play a role in lymphomagenesis.
    Matched MeSH terms: Lymphoma, B-Cell/epidemiology*
  15. Hu S, Qian M, Zhang H, Guo Y, Yang J, Zhao X, et al.
    Blood, 2017 Jun 15;129(24):3264-3268.
    PMID: 28408461 DOI: 10.1182/blood-2017-03-771162
    Publisher's Note: There is an Inside Blood Commentary on this article in this issue.
    Matched MeSH terms: Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  16. Peh SC, Shaminie J, Tai YC, Tan J, Gan SS
    Histopathology, 2004 Nov;45(5):501-10.
    PMID: 15500654
    Follicular lymphoma is frequently associated with t(14;18)(q32;q21) translocation. This study was undertaken to determine the pattern of Bcl-2, CD10 and Bcl-6 expression in relation to t(14;18) translocation in follicular lymphoma from a cohort of a multi-ethnic Asian population.
    Matched MeSH terms: Lymphoma, Follicular/classification; Lymphoma, Follicular/genetics*; Lymphoma, Follicular/immunology*; Lymphoma, Follicular/metabolism
  17. Teoh CS, Lee SY, Chiang SK, Chew TK, Goh AS
    Asian Pac J Cancer Prev, 2018 May 26;19(5):1229-1236.
    PMID: 29801406
    Background: Diffuse large B-cell lymphoma (DLBCL) with double expression of c-MYC and BCL2 protein is
    associated with dismal outcome after treatment with R-CHOP. Local data on disease burden and survival outcome in
    DLBCL is limited. We investigated the prognostic values of c-MYC/BCL2 protein co-expression and cell of origin
    subtypes using immunohistochemistry (IHC) and to determine their associations with multiethnic groups under
    resource limited setting. Methods: This was a retrospective study which recruited 104 patients in between June 2012
    and December 2015 for IHC review and analysis. Result: We demonstrated that patients with high International
    Prognostic Index (IPI) (score 3-5) and co-expression of c-MYC/BCL2 protein had significant inferior overall survival
    (OS) and event free survival (EFS) respectively (P<0.05). c-MYC/BCL2 protein co-expression was more common in
    non-germinal center B-cell (non-GCB) (P=0.048) and contributed to adverse prognosis in this group of patients (OS,
    P=0.004; EFS, P=0.005). In multivariate analysis, double-protein co-expression was a significant independent predictor
    of inferior outcome after adjusted for IPI and cell of origin subtypes (OS hazard ratio [HR], 2.11; 95% CI, 1.01 to 4.04;
    P=0.048; EFS HR, 2.31; 95% CI, 1.05 to 5.04; P=0.036). In addition, non-GCB subtype was more common than GCB
    in Malays (60% vs 40%, P=0.106) and Chinese (81.2% vs 18.8%, P=0.042). Indians had more DLBCL without c-MYC/
    BCL2 protein co-expression compared to double-protein positive cases (66.7% vs 33.3%, P=0.414). Otherwise, the
    prognostic impact of ethnicity on survival outcome was insignificant (P=0.961). Conclusion: c-MYC/BCL2 protein
    co-expression in non-GCB subtype constituted a unique group with extremely inferior outcome regardless of ethnicity.
    Gene expression profile (GEP) may possibly provide insights into the cause of discrepancies in DLBCL subtypes and
    protein expression among the multiethnic groups.
    Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/drug therapy; Lymphoma, Large B-Cell, Diffuse/metabolism; Lymphoma, Large B-Cell, Diffuse/mortality*; Lymphoma, Large B-Cell, Diffuse/pathology*
  18. Vockerodt M, Vrzalikova K, Ibrahim M, Nagy E, Margielewska S, Hollows R, et al.
    J Pathol, 2019 06;248(2):142-154.
    PMID: 30666658 DOI: 10.1002/path.5237
    The Epstein-Barr virus (EBV) is found almost exclusively in the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), yet its contribution to this tumour remains poorly understood. We have focused on the EBV-encoded latent membrane protein-1 (LMP1), a constitutively activated CD40 homologue expressed in almost all EBV-positive DLBCLs and which can disrupt germinal centre (GC) formation and drive lymphomagenesis in mice. Comparison of the transcriptional changes that follow LMP1 expression with those that follow transient CD40 signalling in human GC B cells enabled us to define pathogenic targets of LMP1 aberrantly expressed in ABC-DLBCL. These included the down-regulation of S1PR2, a sphingosine-1-phosphate (S1P) receptor that is transcriptionally down-regulated in ABC-DLBCL, and when genetically ablated leads to DLBCL in mice. Consistent with this, we found that LMP1-expressing primary ABC-DLBCLs were significantly more likely to lack S1PR2 expression than were LMP1-negative tumours. Furthermore, we showed that the down-regulation of S1PR2 by LMP1 drives a signalling loop leading to constitutive activation of the phosphatidylinositol-3-kinase (PI3-K) pathway. Finally, core LMP1-PI3-K targets were enriched for lymphoma-related transcription factors and genes associated with shorter overall survival in patients with ABC-DLBCL. Our data identify a novel function for LMP1 in aggressive DLBCL. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/genetics; Lymphoma, Large B-Cell, Diffuse/metabolism*; Lymphoma, Large B-Cell, Diffuse/mortality; Lymphoma, Large B-Cell, Diffuse/virology
  19. Higuchi H, Yamakawa N, Imadome KI, Yahata T, Kotaki R, Ogata J, et al.
    Blood, 2018 06 07;131(23):2552-2567.
    PMID: 29685921 DOI: 10.1182/blood-2017-07-794529
    Epstein-Barr virus (EBV) causes various diseases in the elderly, including B-cell lymphoma such as Hodgkin's lymphoma and diffuse large B-cell lymphoma. Here, we show that EBV acts in trans on noninfected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between 2 EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata-derived exosomes affected LPD severity, possibly through the regulation of macrophage phenotype in vivo. Exosomes collected from Akata-lymphoblastoid cell lines reportedly contain EBV-derived noncoding RNAs such as BamHI fragment A rightward transcript (BART) micro-RNAs (miRNAs) and EBV-encoded RNA. We focused on the exosome-mediated delivery of BART miRNAs. In vitro, BART miRNAs could induce the immune regulatory phenotype in macrophages characterized by the gene expressions of interleukin 10, tumor necrosis factor-α, and arginase 1, suggesting the immune regulatory role of BART miRNAs. The expression level of an EBV-encoded miRNA was strongly linked to the clinical outcomes in elderly patients with diffuse large B-cell lymphoma. These results implicate BART miRNAs as 1 of the factors regulating the severity of lymphoproliferative disease and as a diagnostic marker for EBV+ B-cell lymphoma.
    Matched MeSH terms: Lymphoma/etiology; Lymphoma/genetics; Lymphoma/immunology; Lymphoma/virology*
  20. Faiz NM, Cortes AL, Guy JS, Reddy SM, Gimeno IM
    J Gen Virol, 2018 07;99(7):927-936.
    PMID: 29767614 DOI: 10.1099/jgv.0.001076
    Marek's disease virus (MDV) is a herpesvirus that induces lymphoma and a variety of non-neoplastic syndromes in chickens. Furthermore, very virulent plus (vv+) MDVs induce a form of immunosuppression (late-MDV-IS) that might involve both neoplastic and non-neoplastic mechanisms. The objective of this study was to evaluate whether the attenuation of MDV-induced tumours and late-MDV-IS occurs simultaneously or can be dissociated. The immunosuppressive ability of three viruses derived from vv+ MDV strain 686 (wild-type 686, the somewhat attenuated molecular clone 686-BAC, and the nononcogenic molecular clone lacking the two copies of the oncogene meq 686-BACΔMEQ) was evaluated. Late-MDV-IS was evaluated indirectly by assessing the negative effect of MDV strains on the protection conferred by infectious laryngotracheitis (ILT) vaccines. Our results showed that the ability to induce late-MDV-IS was attenuated before the ability to induce tumours. Strain 686 induced both tumours and late-MDV-IS, 686-BAC induced tumours but did not induce late-MDV-IS and 686-BACΔMEQ did not induce either tumours or late-MDV-IS. Further comparison of strains 686 and 686-BAC revealed that strain 686 reduced the humoral immune responses to ILTV (1132 vs 2167) more severely, showed higher levels of meq transcripts (2.1E+09 vs 4.98E+8) and higher expression of MDV microRNAs (mdv1-miR-M4-5p and mdv1-miR-M2-3p) in the spleen, and further reduced the percentage of CD45+-MHC-I+splenocytes (13 vs32 %) compared to molecular clone 686-BAC. This study suggests that the immunosuppressive ability of MDV might follow a continuous spectrum and only the most virulent MDVs can overcome a certain threshold level and induce clinical MDV-IS in the ILT model.
    Matched MeSH terms: Lymphoma/genetics; Lymphoma/immunology; Lymphoma/veterinary*; Lymphoma/virology
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