Hub genes and their key effects on prognosis of Burkitt lymphoma

BACKGROUND Burkitt lymphoma(BL)is an exceptionally aggressive malignant neoplasm that arises from either the germinal center or post-germinal center B cells.Patients with BL often present with rapid tumor growth and require high-intensity multidrug therapy combined with adequate intrathecal chemotherapy prophylaxis,however,a standard treatment program for BL has not yet been established.It is important to identify biomarkers for predicting the prognosis of BLs and discriminating patients who might benefit from the therapy.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To identify hub genes and perform gene ontology(GO)and survival analysis in BL.METHODS Gene expression profiles and clinical traits of BL patients were collected from the Gene Expression Omnibus database.Weighted gene co-expression network analysis(WGCNA)was applied to construct gene co-expression modules,and the cytoHubba tool was used to find the hub genes.Then,the hub genes were analyzed using GO and Kyoto Encyclopedia of Genes and Genomes analysis.Additionally,a Protein-Protein Interaction network and a Genetic Interaction network were constructed.Prognostic candidate genes were identified through overall survival analysis.Finally,a nomogram was established to assess the predictive value of hub genes,and drug-gene interactions were also constructed.RESULTS In this study,we obtained 8 modules through WGCNA analysis,and there was a significant correlation between the yellow module and age.Then we identified 10 hub genes(SRC,TLR4,CD40,STAT3,SELL,CXCL10,IL2RA,IL10RA,CCR7 and FCGR2B)by cytoHubba tool.Within these hubs,two genes were found to be associated with OS(CXCL10,P=0.029 and IL2RA,P=0.0066)by survival analysis.Additionally,we combined these two hub genes and age to build a nomogram.Moreover,the drugs related to IL2RA and CXCL10 might have a potential therapeutic role in relapsed and refractory BL.CONCLUSION From WGCNA and survival analysis,we identified CXCL10 and IL2RA that might be prognostic markers for BL.

Testicular Burkitt’s Lymphoma: A Case Report and Literature Review

Background: Burkitt’s lymphoma of the testis (TBL) is a rare and extremely aggressive malignant usually diagnosed in front of a testicular mass. We describe an interesting single case of TBL managed by a combined multimodal approach with a review of the literature. Case Report: A patient aged 69-year-old male, newly hypertensive, who presented with a twelve-month history of right testis progressive painful scrotal swelling, which worsens following a motorbike accident. Clinical examination revealed a large tender mass in an erythematous right scrotal bursa. A scrotal ultrasound showed a right heterogenous intra-testicular mass. The patient underwent unilateral (right) radical orchiectomy. Histopathological examination revealed presence of monomorphic lymphoid cells, with moderate to increased size, dissociated inconstantly by macrophages consistent with a Burkitt’s-like non-Hodgkin Lymphoma. After surgery, the patient was transferred to oncologist for adjuvant chemotherapy. Conclusion: A testicular mass is a usual circumstance for the discovery of a primary tumour of the testicle. Burkitt’s testicular lymphoma is a rare tumour whose diagnosis is based on histological findings. There are non-consensual etiological or predisposing factors. The treatment depends imperatively on the stage of the disease. Therapeutic modalities relay on in surgical excision, chemotherapy and radiation therapy but the accurate procedures are not standardized.

Burkitt Lymphoma Presenting as Ileocolic Intussusception in an Adult

Adult intussusception is rare, highly associated with a malignant lead point, and often requires emergent surgical management. We report the case of a 44-year-old male who presented with generalized abdominal pain and was found to have early ileocolic intussusception secondary to a large ileocecal mass. Biopsies of the mass and an enlarged cardiophrenic lymph node, as well as pleural fluid cytology were all consistent with Burkitt lymphoma (BL). Curiously, the patient’s abdominal exam was reassuring, and the intussusception and malignant bowel obstruction resolved over 36 hours with conservative management alone. With a Burkitt lymphoma international prognostic index (BL-IPI) score of 2, the patient proceeded to treatment with combination chemoimmunotherapy and attained a complete response after four cycles. There was no bowel perforation or recurrent intussusception throughout treatment. Thus, this report marks the first reported case of adult BL-associated intussusception to resolve with non-invasive management and establishes a precedent for conservative management in select patients.

Valproic Acid Enhances the Anti-tumor Effect of(-)-gossypol to Burkitt Lymphoma Namalwa Cells

Burkitt lymphoma is a highly aggressive B-cell neoplasm. New therapeutic methods are needed to overcome the adverse effect of intensive chemotherapy regimens. Valproic acid and （-）-gossypol are two kinds of chemical compounds used as new anti-tumor drugs in recent years.

Modified R-CODOX-M/IVAC chemotherapy regimens in Chinese patients with untreated sporadic Burkitt lymphoma

Objective:To characterize modified R-CODOX-M/IVAC-based chemotherapy to lower the severe adverse events in Chinese adult patients with sporadic Burkitt lymphoma.Methods:We enrolled a retrospective cohort including 123 adult patients with untreated sporadic Burkitt lymphoma from August 2008 to September 2019 at Sun Yat-sen University Cancer Center.We studied a dose-modified and long-course R-CODOX-M/IVAC regimen utilizing a low dose of 1.0 g/m2/cycle cyclophosphamide,2 g/m2/cycle methotrexate,4,500 mg/m2/cycle ifosfamide,and 4.0 g/m2/cycle cytarabine.Forty-nine patients with low risk disease underwent 4–6 cycles of dose-modified R-CODOX-M-based chemotherapy.Seventy-four patients with high risk disease underwent 6–8 cycles of dose-modified alternating R-CODOX-M/IVAC regimens.Results:The objective remission was 87.0%.The event-free survival rate and overall survival at 3 years were 81.2%and 92.1%,respectively.Major grade 3–4 adverse events included leukopenia(91.9%),anemia(58.5%),thrombocytopenia(73.2%),and febrile neutropenia(48.8%).A total of 26.0%and 37.4%of patients received red blood cell and platelet transfusions,respectively.We observed 4 cases(3.3%)of septic shock after chemotherapy.Two treatment-related deaths occurred from severe infection.Conclusions:The modified R-CODOX-M/IVAC chemotherapy regimen was effective for sporadic Burkitt lymphoma in the Chinese population,with a lower toxicity than standard regimens.

Clinical presentation of gastric Burkitt lymphoma presenting with paraplegia and acute pancreatitis:A case report

BACKGROUND The incidence of gastric Burkitt lymphoma(BL),presenting as paraplegia and acute pancreatitis,is extremely low.BL is a great masquerader that presents in varied forms and in atypical locations,and it is prone to misdiagnosis and missed diagnosis.The prognosis of BL remains poor because of the difficulty in early diagnosis and the limited advances in chemotherapy.CASE SUMMARY A 53-year-old man was referred to our hospital from the local county hospital due to abdominal pain for two weeks and weakness in the lower extremities for one day.Magnetic resonance imaging of the abdomen and lumbar spine showed a swollen pancreas and gallbladder,with peripancreatic exudation and liquid collection,indicating acute pancreatitis and acute cholecystitis.Additionally,we observed abnormally thickened lesions of the gastric wall,multiple enlarged retroperitoneal lymph nodes and a well-demarcated,posterolateral extradural mass lesion between T9 and T12,with extension through the spinal foramen and definite bony destruction,suggesting metastasis in gastric malignancy.Subsequent whole-body positron emission tomography/computed tomography examination showed multifocal malignant lesions in the stomach,pancreas,gallbladder,bone,bilateral supraclavicular fossa,anterior mediastinum,bilateral axillary and retroperitoneal lymph nodes.Gastroduodenal endoscopy revealed primary BL with massive involvement of the gastric body and duodenum.The patient refused chemotherapeutic treatment and died one week later due to upper gastrointestinal hemorrhage.Afterward,we reviewed the characteristics of 11 patients with BL involving the stomach,pancreas or spinal cord.CONCLUSION Clinicians should be aware that BL can be the potential cause of acute pancreatitis or a rapidly progressive spinal tumor with accompanying paraplegia.For gastric BL,gastroscopy biopsies and pathology are necessary for a definite diagnosis.

Secondary peripheral T-cell lymphoma and acute myeloid leukemia after Burkitt lymphoma treatment:A case report

BACKGROUND Multiple primary cancer refers to more than one synchronous or sequential cancer in the same individual.Multiple primary cancer always presents as solid cancer or acute myeloid leukemia(AML)secondary to lymphoma.Here,we report a rare case of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment.CASE SUMMARY A 54-year-old female patient was admitted to our hospital complaining of edema on her left lower limb.Physical examination revealed multiple superficial lymphadenectasis on her neck and pelvis.Color ultrasonography examination showed multiple uterine fibroids and a solid mass at the lower left side of the abdomen.Pathological biopsy revealed Burkitt lymphoma.After three hyper-CVAD(A+B)regimens,she achieved complete remission.Two years later,lymphadenectasis reoccurred.A relevant biopsy confirmed the diagnosis of peripheral T-cell lymphoma,which was accompanied by gastrointestinal invasion and hemocytopenia.Meanwhile,bone marrow examination revealed AML.On the second day of scheduled treatment,she developed gastrointestinal bleeding,peptic ulcers,and hemorrhagic shock and was critically ill.She was then discharged from the hospital due to financial concerns.CONCLUSION This is the first report of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment with heterochronous and synchronal multiple primary cancers.

Gallbladder Burkitt's lymphoma mimicking gallbladder cancer:A case report

BACKGROUND Malignant lymphoma is a rare form of gallbladder malignancy.Most of these malignancies are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas;however,Burkitt’s lymphoma of the gallbladder is extremely rare,and only two previous reports are available in the literature.Herein,we report a rare case of Burkitt’s lymphoma of the gallbladder mimicking gallbladder adenocarcinoma.CASE SUMMARY An 83-year-old man with no abdominal complaints was found to have a gallbladder tumor and periportal lymph node enlargement on computed tomography(CT)performed for hypertension screening.His laboratory data revealed slightly elevated serum levels of carcinoembryonic antigen and soluble interleukin 2 receptor.Imaging examinations revealed two irregular and contrastenhanced masses extending into the gallbladder lumen,but these did not infiltrate the serosa.Moreover,a periportal lymph node had enlarged to 30 mm.Based on these findings,we diagnosed the patient as having gallbladder adenocarcinoma with lymph node metastasis,which was treated using bile duct resection with gallbladder bed resection and periportal lymph node dissection.However,the patient was finally diagnosed as having Burkitt’s lymphoma.Although the surgical margin was pathologically negative,recurrence was noted at the hepatic radical margin and superior pancreaticoduodenal lymph nodes on positron emission tomography/CT soon after discharge.Thus,he was referred to a hematologist and started receiving treatment with reduced-dose cyclophosphamide,doxorubicin,vincristine,and prednisone.CONCLUSION Burkitt’s lymphoma can occur in the gallbladder.Biopsy can be useful in cases with findings suggestive of gallbladder malignant lymphoma.

Prostatic Burkitt Lymphoma, a Rare Secondary Location

Introduction: Non-Hodgkin’s malignant lymphoma is found primarily in African children. Prostate localization is a rare entity. We report the case of a secondary prostatic localization of Burkitt lymphoma in a 14-year-old child. Observation: the 14-year-old child NNJ was followed at the Libreville Cancer Institute (ICL) for Burkitt maxillo-facial stage II bilateral Murphy lymphoma. The clinical examination noted an alteration of the general state, total hematuria, a voluminous prostatic mass filling the rectal ampoule. The paraclinical assessment noted renal insufficiency, a prostatic mass on ultrasound. Anatomo-pathological examination of the prostatic biopsy diagnosed Burkitt type non-Hodgkin’s malignant lymphoma. He died a week later. Conclusion: Primary or secondary prostatic lymphoma is rare. Obstructive renal insufficiency is an additional complication that darkens its prognosis by delaying etiological treatment based on polychemotherapy.

Regulatory Effects of Deguelin on Proliferation and Cell Cycle of Raji Cells

Summary： The underlying mechanism of deguelin regulating the cell cycle in human Burkitt＇s lym phoma cell line Raji cells in vitro, and the cytotoxicity of deguelin to Raji cells and human peripheral blood monocular cells （PBMCs） were investigated. The effects of deguelin on the growth of Raji cells were studied by 3-（4, 5-dimethyl-2-thiazolyl）-2,5-diphenyl-2H-tetrazolium （MTT） assay. Apoptosis was detected through Hoechst 33258 staining. The effect of deguelin on the cell cycle of Raji cells was studied by a propidium iodide method. The expression levels of cyclin D1, P21 and pRb were examined by using Western blotting. The results showed that the proliferation of Raji cells was inhibited in the de guelin-treated group, with a 24-h IC5o value of 21.61 nmol/L and a 36-h IC50 value of 17.07 nmol/L. Proliferation in Raji cells was inhibited significantly by deguelin, while little change was observed in PBMCs. Deguelin induced G2/M arrest in Raji cells. The expression of cyclin D1, P21 and pRb was dramatically down-regulated by deguelin in a dose-dependent manner. It was concluded that deguelin could inhibit the proliferation of Raji cells by arresting the cells at GE/M phase and inducing the cell apoptosis. Moreover, deguelin selectively induced apoptosis of Raji cells with low toxicity to PBMCs. The antitumor effects of deguelin were related to the down-regulated expression of cyclin D1, P21 and pRb proteins.

Trichostatin A Regulates hGCN5 Expression and Cell Cycle on Daudi Cells in vitro

The expression of human general control of amino acid synthesis protein 5 （hGCN5） in human Burkitt＇s lymphoma Daudi cells in vitro, effects of Trichostatin A （TSA） on cell proliferation and apoptosis and the molecular mechanism of TSA inhibiting proliferation of Daudi cells were investigated. The effects of TSA on the growth of Daudi cells were studied by 3-（4, 5-dimethyl-2-thiazolyl）-2,5-diphenyl-2H-tetrazolium （MTT） assay. The effect of TSA on the cell cycle of Daudi cells was assayed by a propidium iodide method. Immunochemistry and Western blot were used to detect the expression of hGCN5. The proliferation of Daudi cells was decreased in TSA-treated group with a 24 h IC50 value of 415.3979 μg/L. TSA induced apoptosis of Daudi cells in a timeand dose-dependent manner. Treatment with TSA （200 and 400 μg/L） for 24 h, the apoptosis rates of Daudi cells were （14.74±2.04） % and （17.63±1.25） %, respectively. The cell cycle was arrested in G0/G1 phase （50, 100 μg/L） and in G2/M phase （200 μg/L） by treatment with TSA for 24 h. The expression of hGCN5 protein in Daudi cells was increased in 24 h TSA-treated group by immunochemistry and Western blot （P〈0.05）. It was suggested that TSA as HDACIs could increase the expression of hGCN5 in Daudi cells, and might play an important role in regulating the proliferation and apoptosis of B-NHL cell line Daudi cells.

One Month Ongoing Intussusception: Case Report

The aim is to present a case operated due to one-month ongoing intussusception and diagnosed as lymphoma. A six years old boy was admitted to our emergency department with complaint of colicky abdominal pain and bilious vomiting for the last month. He was operated due to 3 cm intussusception at ileocecal part. A mass which is about 6 cm in diameter, hard, partly mobile and invaginate the intestine at its posterior aspect was found. Pathology was reported as Burkitt lymphoma. He received two cycles of chemotherapy at post-operative period. He is still event free for the last two years. One must remember that lymphoma can be the lead point in intussusception especially in elderly children.

Treatment outcome in children with central nervous system-positive Burkitt lymphoma using only intrathecal and systemic chemotherapy combined with rituximab

Background:With current chemotherapy treatment,>90%of survival has been obtained for Burkitt lymphoma(BL).In this study,the demographic characteristics and treatment outcomes are presented for 78 children in China with central nervous system-positive(CNS+)BL.Methods:This retrospective study consecutively enrolled 78 CNS+BL patients in Beijing Children’s Hospital(BCH)from 2007 to 2019 who received the BCH B-cell non-Hodgkin’s lymphoma regimen(modified by French-American-British mature lymphoma B-cell 96[FAB/LMB96]C1 arm±rituximab).Clinical characteristics,methods of disease detection in the CNS,and outcomes were evaluated.Univariate and multivariate analyses were used to assess prognostic factors.Results:The median age of 65 boys and 13 girls at the time of diagnosis was 5.7 years(ranging from 1 to 14 years).Patients were followed up for a median time of 34 months(ranging from 1 to 72 months).Bone marrow invasion was found in 38(48.7%)patients.There were 48(61.5%),44(56.4%),and 25(32%)patients with cranial nerve palsy,intracerebral mass(ICM),and parameningeal extension,respectively.Abnormal cerebrospinal fluid(CSF)morphology and CSF immunophenotype appeared in 15(19.2%)and 15(19.2%)patients,respectively.There were 69(88.5%)patients treated with chemotherapy combined with rituximab,and nine patients were treated solely with chemotherapy.Finally,five patients died of treatment-related infection,recurrence occurred for 13,and one developed a second tumor.The 3-year overall survival and event-free survival rates were 78.9%±4.7%and 71.4%±6.0%,respectively.Treatment with chemotherapy only,ICM positivity,and>4 organs involved at diagnosis were independent risk factors.Conclusions:Rituximab combined with a modified LMB96 regimen has greatly increased the efficacy of treatment for Chinese children with CNS+BL,and with the continuous collection of outcome data,treatment-related complications are decreasing.For further verification,a large sample multicentre randomized controlled study should be performed to explore a treatment scheme for Chinese children with even greater efficacy.

Clinicopathological Study of Sporadic Burkitt Lymphoma in Children

Background：Non-Hodgkin lymphoma is the fourth most common malignant tumors in children,Burkitt lymphoma （BL） accounts for 30-50％ of all pediatric lymphomas.The aim of this study was to investigate the clinicopathologic features,immunophenotype,Epstein-Barr virus （EBV） infection and c-myc gene rearrangement of sporadic BL in children.Methods：Ninety-two cases of pediatric BL were retrospectively analyzed for clinical features,immunohistochemistry,EBV-encoded RNA （EBER） status by in situ hybridization and c-myc gene rearrangement by fluorescence in situ hybridization.Results：In the 92 cases,male is predominant in sex distribution （M：F =3.38：1）.The average age at diagnosis was 4.97 years.Polypoid BL showed a lower clinical stage （P =0.002）,and advanced clinical stage and low serum albumin level at diagnosis were associated with poor outcome （P =0.024 and 0.053,respectively）.The positive expression of CD10,B-cell lymphoma-6,MUM1 and EBER were 95.7％ （88 cases）,92.4％ （85 cases）,22.8％ （21 cases）,41.3％ （38 cases）,respectively.The expression of MUM1 were not associated with EBV infection status （P =1.000）.c-myc gene rearrangement was detected in 94.6％ （87/92）.Clinical treatment information for 54 cases was collected,21 patients died of tumor after surgery alone,33 patients received surgery and chemotherapy,and of which six patients died shortly afterwords （MUM 1 positive expression in 3 cases,P =0.076）.Conclusions：The anatomical location,growth pattern and serum albumin level of BL were associated with biological behavior.MUM1 may be a potential adverse prognostic marker,and not associated with EBV infection status.

Outcomes of Burkitt lymphoma with bone marrow involvement or Burkitt leukemia in Chinese children

Importance Burkitt lymphoma with bone marrow involvement and Burkitt leukemia behave aggressively.Thus far,there are limited data concerning survival and toxicity in Chinese children with Burkitt lymphoma or Burkitt leukemia who have undergone treatment with the non-Hodgkin’s lymphoma Berlin-Frankfurt-Münster-90/95(NHL-BFM-90/95)protocol.Objective To analyze outcomes and toxicity in pediatric patients who exhibit Burkitt lymphoma with bone marrow involvement or Burkitt leukemia following treatment with the NHL-BFM-90/95 protocol.Methods Patients aged<18 years with bone marrow involvement/leukemia who were treated with the NHL-BFM-90/95 protocol,with or without rituximab,in Sun Yat-Sen University Cancer Center from April 2004 to December 2018 were included in this retrospective analysis.Results Twenty-five patients were eligible.Burkitt lymphoma with bone marrow involvement and Burkitt leukemia were present in 10 and 15 patients,respectively.Central nervous system infiltration was not observed in any patients.All patients underwent chemotherapy involving NHL-BFM-90/95 protocol.Six courses of treatment were administered to each patient(v-AA-BB-CC-AA-BB-CC).The BFM-90/95 plus rituximab protocol was administered to 13 patients.The median follow-up interval was 31.9 months(range,2.5–158 months).Of the 25 patients,four died:three died of tumor progression and one died of therapy abandonment after relief of tumor lysis syndrome.The estimated 5-year event-free survival and overall survival rates were both 85.8%±5.0%.Interpretation Chinese pediatric patients who exhibit Burkitt lymphoma with bone marrow involvement or Burkitt leukemia can achieve optimal treatment outcomes and exhibit good tolerance when using the NHL-BFM-90/95 protocol.

Reversible Posterior Leukoencephalopathy Syndrome Sometimes Could be Irreversible： A Case Following Tumor Lysis Syndrome in Childhood Burkitt＇s Lymphoma

Reversible posterior leukoencepbalopathy syndrome （RPLS） was first described by Hinchey eta/. in 1996 as a clinical radiologic syndrome consisting of reversible cortical neuroIogic dysIhnction and brain imaging findings involving the posterior circulation, especially the occipital lobes.