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.

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.

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.

Epstein-Barr virus and Burkitt lymphoma

In 1964,a new herpesvirus,Epstein-Barr virus(EBV),was discovered in cultured tumor cells derived from a Burkitt lymphoma(BL)biopsy taken from an African patient.This was a momentous event that reinvigorated research into viruses as a possible cause of human cancers.Subsequent studies demonstrated that EBV was a potent growth-transforming agent for primary B cells,and that all cases of BL carried characteristic chromosomal translocations resulting in constitutive activation of the c-MYC oncogene.These results hinted at simple oncogenic mechanisms that would make Burkitt lymphoma paradigmatic for cancers with viral etiology.In reality,the pathogenesis of this tumor is rather complicated with regard to both the contribution of the virus and the involvement of cellular oncogenes.Here,we review the current understanding of the roles of EBV and c-MYC in the pathogenesis of BL and the implications for new therapeutic strategies to treat this lymphoma.

Tumor Lysis Syndrome in the Course of Burkitt Lymphoma Revealed by Medullar Compression

Background: Tumor lysis syndrome is unknown to many neurosurgical teams. A dreaded complication, especially in the course of hematological malignancies, like it was the case in two of our patients operated for spinal cord compression by Burkitt’s lymphoma. Objectives: To describe the clinical and biological presentation of this potentially fatal complication, which can be improved by early preventive or curative treatments. Case Reports: Patient 1: A 49-year-old woman was admitted for vertebral and intercostal pain and paraparesis. Myelography revealed epidural medullary compression at the 7th thoracic vertebrae (Th7) level. Patient 2: A 67-year-old woman was admitted for cervico-thoracic pain and paraparesis. MRI showed posterior epidural medullary compression between the 1st thoracic vertebrae (Th1) and 5th thoracic vertebrae (Th5). In both cases, an urgent decompressive laminectomy was performed. They had also received postoperative corticosteroid therapy. The multi-visceral failure occurred on the 1st day (D1) and 3rd day (D3) postoperatively, respectively. In the absence of adequate management, the outcome was fatal for the two patients respectively at D3 and D5 postoperatively. This syndrome was retained in the presence of glucocorticoid (triggering factor) and the histological result in favor of Burkitt lymphoma (target disease). Conclusion: Malignant hemopathies is a common cause of spinal cord compressions. From these two cases, the importance of biological and clinical surveillance emerges, with patients requiring urgent management for radiculo-medullar tumor compression.

奥妥珠单抗联合化疗治疗多线化疗后进展且塞利尼索无效的TP53突变Burkitt淋巴瘤

Burkitt淋巴瘤是一种高度侵袭性的非霍奇金B细胞淋巴瘤(B-NHL),其特征为IGH/MYC基因易位及MYC蛋白高表达。多线化疗后进展且在使用小分子核输出蛋白1(XPO1)抑制剂塞利尼索后仍无效的TP53突变Burkitt淋巴瘤是目前的治疗难点,可选择的治疗方案十分有限,目前仍无有效治疗手段,且预后极差。本文报道伴TP53突变Burkitt淋巴瘤多线化疗后进展且塞利尼索治疗无效的患者2例。患者均接受奥妥珠单抗(G)联合二线方案治疗(1例G-DA-EPOCH方案、1例Ibru+GB方案),目前疗效评估均达到完全缓解(CR),主要不良反应为输液相关反应,经对症支持治疗后明显缓解。以奥妥珠单抗为代表的新药治疗可为目前多线化疗后进展且塞利尼索无效的TP53突变Burkitt淋巴瘤患者的治疗提供参考。

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.

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.

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.

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.

Mangiferin联合硼替佐米对Burkitt淋巴瘤恶性生物学行为的调控机制及对CXCR表达的影响

目的:分析芒果苷(mangiferin)联合硼替佐米对人Burkitt淋巴瘤Raji细胞增殖、侵袭、凋亡和自噬的作用及对CXC趋化因子受体家族(CXCR)表达的影响,并探究其间存在的分子机制,为Burkitt淋巴瘤基础研究与临床提供科学依据。方法:采用不同浓度Mangiferin、硼替佐米单药或联合干预Raji细胞,利用CCK-8法检测细胞增殖,Transwell小室法检测细胞侵袭能力,Annexin V/PI双染流式细胞术检测细胞凋亡,Western blot检测凋亡、自噬及Akt/m TOR通路蛋白表达情况,实时荧光定量PCR检测CXCR家族的表达变化。结果:不同浓度Mangiferin干预Raji细胞不同时间后,可抑制Raji细胞活力,且呈浓度及时间依赖性(r=-0.682,r=-0.836);与单药组相比,Mangiferin联合硼替佐米干预Raji细胞时,细胞增殖与侵袭能力显著下降、凋亡水平显著升高(P<0.01)。Mangiferin联合硼替佐米干预Raji细胞后,可上调促凋亡蛋白Bax表达并显著下调抗凋亡蛋白Bcl-2的表达,同时亦使Caspase-3水解活化,继而诱导Raji细胞发生凋亡。Mangiferin联合硼替佐米干预Raji细胞后可上调LC3Ⅱ蛋白的表达,且细胞中LC3Ⅱ/LC3Ⅰ比值较单药或对照组显著上调(P<0.01)。Mangiferin联合硼替佐米可显著抑制Akt和m TOR的磷酸化水平,通过抑制Akt/m TOR通路来使Raji细胞增殖及侵袭受抑,并诱导细胞发生自噬与凋亡。Mangiferin及硼替佐米单药干预Raji细胞后,可下调CXCR4、CXCR7 m RNA的表达,当两药联合时CXCR4、CXCR7 m RNA表达下调更为显著(P<0.01)。Mangiferin单药或联合硼替佐米干预Raji细胞后CXCR5 m RNA表达无显著变化(P>0.05),但两药联合时可使CXCR3表达下调(P<0.05)。结论:Mangiferin联合硼替佐米能协同抑制Raji细胞增殖、侵袭,并诱导其发生自噬与凋亡,机制可能与抑制Akt/m TOR信号通路并通过下调抗凋亡蛋白Bcl-2和上调促凋亡蛋白Bax以及使CXCR家族表达受抑等有关。

Prognostic values of interim and post-therapy ^(18)F-FDG PET/CT scanning in adult patients with Burkitt's lymphoma

Background:The prognostic values of interim and post-therapy fluorine-18-fluorodeoxyglucose(^(18)F-FDG) positron emission tomography(PET) and PET/computed tomography(CT) scanning have been confirmed in several subtypes of lymphoma.However,its prognostic value in Burkitt's lymphoma has not been clearly defined.The aim of the present study was to assess the prognostic value of PET/CT scanning during different treatment processes of Burkitt's lymphoma.Methods:A total of 29 adult patients with newly diagnosed Burkitt's lymphoma were retrospectively involved in this study;of them,23 patients underwent baseline PET/CT,15 patients underwent mid-therapy PET/CT after 1-4 cycles of chemotherapy,and 17 patients underwent post-therapy PET/CT after all planned first-line chemotherapy cycles.Mid-therapy and post-therapy PET/CT results(positive vs.negative) were visually interpreted according to the criteria of the International Harmonization Project.The reduction in the maximum standardizes uptake values(ASUVmax)of 25%,50%,and 75%were regarded as cutoff points.Overall survival(OS) and progression-free survival(PFS) were regarded as the major endpoints.Results:The median OS and PFS were 27.6 months(range 6.5-78.3 months) and 27.2 months(range 3.0-78.3 months),respectively.The median SUVmax of the baseline PET/CT was 18.3(range 1.6-35.9),whereas the median SUVmax of the mid-therapy and post-therapy PET/CT decreased to 4.0(range 0-17.6) and 3.0(range 0-14.5),respectively.The patients' Eastern Cooperative Oncology Group(ECOG) scores(<2 vs.≥2) were significantly associated with the baseline PET/CT SUVmax.The mid-therapy and post-therapy PET/CT results(positive vs.negative) showed no significant association with OS or PFS.The optimal cutoff ASUVmax from the baseline to the post-therapy PET/CT that could predict a change in OS in patients with Burkitt's lymphoma was 50%(P = 0.019).Conclusions:^(18)F-FDG uptake was intense in Burkitt's lymphoma,and there was a significant reduction in SUVmax during the interim and post-therapy PET/CT procedures.A ASUVmax of greater than 50%was a favorable cutoff point to predict the OS of Burkitt's lymphoma patients.

Complete remission of gastric Burkitt's lymphoma after eradication of Helicobacter pylori

Burkitt’s lymphoma is a highly aggressive nonHodgkin lymphoma, often presenting in extra-nodal sites. It generally has a poor spontaneous outcome and needs aggressive treatment with systemic and intrathecal chemotherapy. Occurrence at the gastric site is rare. We report the case of a 39-year old woman who presented with a prominent ulcerated lesion of the antrum corresponding histologically to a Burkitt’s lymphoma associated with Helicobacter pylori (H pylori) infection. Interphase fluorescence in situ hybridization (FISH) demonstrated c-MYC gene rearrangement in tumour cells without BCL2 or BCL6 gene translocations. Ulcer healing and tumour regression with a complete histological response were obtained 8 wk after H pylori eradication. In spite of this complete remission, taking into account the high risk of recurrence, the patient received systemic and intrathecal chemotherapy. Two years later, the patient remained in complete remission. This is the first report of a gastric Burkitt’s lymphoma responding to H pylori eradication. These findings raisethe question of the potential role of H pylori in the pathogenesis of some gastric Burkitt’s lymphomas, and show the importance of searching for and eradicating the bacteria in combination with conventional chemo-therapy regimens.

褪黑素促进Burkitt淋巴瘤细胞对阿霉素的化疗敏感性

目的探讨褪黑素(Melatonin,MEL)增强阿霉素(Adriamycin,ADM)抑制Burkitt淋巴瘤(Burkitt lymphoma,BL)细胞CA46的作用机制。方法使用不同浓度MEL(分为不加药组,0.5 mM组,1 mM组,2 mM组,4 mM组)分别处理CA466 h、12 h、24 h,使用ADM(分为不加药组,0.1μg/L组,0.2μg/L组,0.4μg/L组,0.8μg/L组,1.6μg/L组)处理CA4624 h,采用CCK8法检测细胞存活率并计算半数抑制率(half inhibition concentration,IC50)。同时,单用0.1μg/L ADM(ADM组),联用1 mM MEL和0.1μg/L ADM(AAM组)处理CA4624 h后,检测IC50的变化。使用蛋白印迹(Western Blotting,WB)实验检测不同浓度的MEL(分别为不加药组,0.5 mM组,1 mM组,2 mM组)处理CA4624 h后对NF-κB蛋白表达量的影响。WB法检测1 mM MEL处理CA4624 h(MEL组),ADM组,AAM组以及不加药组(Control组),WB法检测Nrf2,LC3B和p62蛋白的表达水平。结果MEL对CA46的抑制作用存在时间依赖性和浓度依赖性(P<0.05),同时降低了NF-κB蛋白的表达(P<0.05);同样ADM对CA46的抑制作用存在浓度依赖性(P<0.05);1 mM MEL处理CA466 h、12 h、24 h的IC50分别为(6.170±0.648)mM、(2.205±0.093)mM、(1.297±0.197)mM。ADM组和AAM组中ADM的IC50分别是(1.256±0.080)μg/L和(0.503±0.026)μg/L。AAM组相对于ADM组降低了Nrf2和p62的相对表达量(P<0.05),增强了LC3Ⅱ/LC3Ⅰ比值(P<0.05)。结论MEL增强ADM对CA46的抑制作用,其作用机制与抑制Nrf2/p62信号通路及增强自噬有关。

THE DNase-1 SENSITIVE REGIONS IN GENOMES OF BURKITT' S LYMPHOMA CELLS

This article reported the distribution of DNase-1 sensitive regions in genomes of three Burkitt's lymphoma cell lines, P3HR-1, Raji and Ramos cell lines using a new method of in situ nick translation of chromosomes substituted completely by BrdU. The results showed that the Blym locus on chromosomes In three cell lines and the c-myc locus on chromosomes in P3HR-1 were the DNase-1 sensitive regions and found that the rearrangemental sites of chromosomes present in three Burkltt' s lymphoma cell lines were sensitive to DNase-1 digestion, Indicating that c-myc, bcl-1 genes located at the rearrangemental sites and the Blym gene in Burkltt' s lymphoma are the active genes having the capability of expression.