The relationship between PM20D1 gene and hypoxia and prognosis in diffuse large B-cell lymphoma was analyzed by integrating multiple databases / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨肽酶M20结构域1（peptidase M20 domain containing 1，PM20D1）在人弥漫大B细胞淋巴瘤（diffuse large B-cell lymphomas，DLBCL）细胞中的表达及其与缺氧相关性和预后的关系。方法：通过GDC、TCGA、GTEx公共数据库分析PM20D1表达对DLBCL细胞增殖、迁移和凋亡的影响及其与患者预后的关系。通过对不同分组患者的富集分析及PM20D1与CD274相关性分析验证PM20D1是否为DLBCL的缺氧相关基因；采用ChEA、ENCODE和hTFtarget数据库分析上游调控PM20D1表达的转录因子（TF）和miRNA，以及差异表达PM20D1与化疗药物敏感性的关系。采用WB法检测PM20D1在正常淋巴细胞和DLBCL细胞中的表达水平，通过设计PM20D1的siRNA序列敲减目的基因，并采用qPCR和WB法检测验证SUDHL2和SUDHL10细胞中PM20D1的敲减效率，采用CCK-8法和Transwell实验分别检测敲减PM20D1对细胞增殖和迁移能力的影响，流式细胞术检测细胞凋亡水平。结果：PM20D1在DLBCL组织中高表达且患者预后差（P<0.05或P<0.01）；富集分析显示，PM20D1高表达组与ssGSEA高分组主要涉及细胞电耦合通讯、甘油三酯代谢过程调节和细胞质翻译起始复合物过程，且PM20D1表达与免疫检查点CD274表达呈正相关（P<0.01，r=0.757）。在SUDHL2和SUDHL10细胞中敲减PM20D1后，细胞的增殖和迁移均显著降低（均P<0.05），细胞凋亡明显增加（P<0.05）。结论：PM20D1基因在DLBCL组织和细胞中高表达且与患者预后密切相关；PM20D1可能通过促进DLBCL细胞的增殖、迁移并抑制凋亡，从而促进DLBCL的发生发展。

18F-FDG PET/CT Prognostic Role in Diffuse Large B-cell Lymphoma Following Chemotherapy / 中山大学学报(医学科学版)

ObjectiveTo assess the prognostic value of 18F-FDG PET/CT parameters for predicting therapeutic response in diffuse large B-cell lymphoma （DLBCL）. MethodsWe retrospectively analyzed the clinical data and 18F-FDG PET/CT radiomics features of 81 DLBCL patients enrolled between June 2015 and October 2020. Multivariate logistic regression analysis was used to identify the predictive factors for therapeutic response of DLBCL， based on which a predictive model was developed accordingly. The performance of the model was evaluated by receiver operating characteristic （ROC） curves and calibration plots. ResultsDuring the two years after first chemotherapy， 23 patients （28.3%） developed relapse and 58 patients （71.7%） had progression-free survival （PFS）. The analysis for the predictive capability of the binary logistic regression model incorporating the PET/CT features revealed that the imaging features of 18F-FDG PET/CT after chemotherapy were independent prognostic factors for PFS. Among them， SUVTHR-mean2 was the most important factor for predicting therapeutic response in DLBCL patients after chemotherapy， with a cutoff value of 2.00 （AUC=0.81）. Conclusions18F-FDG PET/CT showed a valuable prognostic performance for PFS in DLBCL patients after chemotherapy， with the imaging feature after chemotherapy SUVTLR-mean2 being the optimal independent predictor. Our predictive model of imaging features might have an important prognostic value in assessing the risk of disease progression， guiding the treatment and follow-up protocol， improving therapeutic efficiency and cutting down the medical cost.

Effect of Qiling Baitouweng Tang on Proliferation and Apoptosis in Diffuse Large B-cell Lymphoma Through JAK2/STAT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Qiling Baitouweng Tang （QLBTWT） on proliferation and apoptosis， Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway and interleukin-10 （IL-10） in diffuse large B-cell lymphoma （DLBCL）. MethodWith human DLBCL cells OCI-LY10 and U2932 as research objects， cell proliferation was detected by cell counting kit-8 （CCK-8） assay. After treatment with 0， 4.6， 9.3， 18.7， 37.5， 75， 150 mg·L-1 QLBTWT for 24 h， the half-inhibitory concentration （IC50） of OCL-LY10 and U2932 cells was calculated to be 9.33， 16.13 mg·L-1， respectively， based on which， 9.5， 19， 38 mg·L-1 QLBTWT were selected for subsequent experiments. After 0， 9.5， 19， 38 mg·L-1 QLBTWT treatment for 24 h， the zymogen activities of Caspase-3， Caspase-8 and Caspase-9 in OCI-LY10 and U2932 cells were detected using corresponding activity assay kits （colorimetric）， and the IL-10 expression was detected by enzyme-linked immuno sorbent assay （ELISA）. The apoptosis rate and cell cycle of OCI-LY10 and U2932 cells treated with different concentrations of QLBTWT for 24 h were detected by flow cytometry. The expressions of apoptosis-related proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved poly adenosine diphosphate ribose polymerase （cleaved PARP）， cleaved Caspase-3］， JAK2， STAT3， phospho-JAK2 （p-JAK2）， phospho-STAT3 （p-STAT3） pathway proteins， and c-Myc protein in OCL-LY10 and U2932 cells after 24 h treatment with 0， 9.5， 19， 38 mg·L-1 QLBTWT were all tested by Western blot. ResultAfter QLBTWT treatment on OCI-LY10 and U2932 cells for 24 h， cell proliferation was inhibited in each QLBTWT group compared with that in the control group （P<0.05， P<0.01）. The zymogens of Caspase-3， Caspase-8 and Caspase-9 were activated （P<0.01）， and there was an increase in cell apoptosis （P<0.05， P<0.01） and cell cycle arrest at Gap phase1 （G1） phase in 9.5， 19 and 38 mg·L-1 QLBTWT group （P<0.05， P<0.01）. After 9.5， 19 and 38 mg·L-1 QLBTWT treatment on OCI-LY10 and U2932 cells for 24 h， the expressions of Bcl-2， p-JAK2 and p-STAT3 proteins were decreased （P<0.01）， and the expressions of Bax， cleaved PARP and cleaved Caspase-3 proteins were increased （P<0.01）， but no significant change was observed in the expressions of JAK2 and STAT3 proteins. Compared with the conditions in the control group， the expressions of c-Myc， p-JAK2， and p-STAT3 proteins were down-regulated in 19 mg·L-1 QLBTWT group and 19 mg·L-1 QLBTWT+10 μg·L-1 IL-10 group （P<0.05， P<0.01）， and up-regulated in 10 μg·L-1 IL-10 group （P<0.05， P<0.01）， while there was no difference in JAK2/STAT3 proteins. ConclusionQLBTWT can inhibit proliferation and induce apoptosis of human DLBCL cells OCI-LY10 and U2932， and the potential mechanism may be related to the regulation of JAK2/STAT3 signaling pathway.

A novel IRAK4/PIM1 inhibitor ameliorates rheumatoid arthritis and lymphoid malignancy by blocking the TLR/MYD88-mediated NF-κB pathway

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

Clinical significance of LncRNA-MIAT as a non-invasive diagnostic marker of nonHodgkin's lymphoma associated with occult hepatitis C virus infection

Aims: the current research aimed to investigate LncRNA-MIAT in patients with nonHodgkin lymphoma (NHL) and to assess its correlation with clinicopathological features and treatment protocols of NHLs among Egyptian patients with Occult hepatitis C virus (HCV) infection (OCI). Patients & Methods: This study was conducted on 20 patients with NHL and 30 healthy subjects as the control group. All subjects were screened for HCV-RNA in both plasma and PBMCs. RT-PCR determined lncRNA-MIAT. Results: lncRNA-MIAT relative expression level was upregulated in NHL groups (2.73±0.86) compared to controls (1.06±0.07), P ˂0.001*. Among NHL, patients with OCI (3.2±0.63) had significantly higher levels of lncRNA-MIAT compared to HCV (2.6±1.08) and non-HCV (2.4±0.4), P ˂0.001*. Additionally, the relative expression levels of lncRNA-MIAT were significantly positively correlated with laboratory and clinicopathological features of NHL. Interestingly, concerning the treatment of DLBCLNHL, there were significantly higher levels of lncRNA-MIAT in no treatment subgroup (n=10, 3.31±0.95) compared to successfully treated subgroups [CHOP (n=7, 1.58±0.34) and R-CHOP (n=3, 11.16±0.21), P ˂0.001* Conclusions: lncRNA-MIAT level was upregulated in NHL patients, particularly patients with OCI. Thus, circulatory lncRNA-MIAT may serve as a promising non-invasive diagnostic marker for NHL associated with OCI

Analysis of correlation between the number of circulating DLBCL cells and marrow tumor burden by FCM and its clinical significance / 中华检验医学杂志

Objective:To investigate the correlation between the number of circulating DLBCL cell and the marrow tumor cell burden and the prognostic indicators in patients with DLBCL, and to evaluate the feasibility of circulating DLBCL cell reflecting the marrow tumor burden and disease progression. Optimization of FCM for screening circulating DLBCL cell was done to monitor MRD and recurrence.Methods:We conducted a retrospective study in 75 diagnosed DLBCL patients in the First Affiliated Hospital of Zhengzhou University from June 2020 to February 2021, including 43 males and 32 females aged 61 (37-85) years. According to the diagnosis and treatment criteria, the patients were divided into initial and recurrence group ( n = 53), partial response(PR)group ( n=14) and complete response(CR)group ( n=8). According to the positive criteria of circulating DLBCL cells, 48 cases were divided into circulating DLBCL positive group and 27 cases were negative group. 30 anemia patients with non-B-cell tumor-related diseases were selected as the control group, including 16 males and 14 females, aged 52 (30-79) years. 70 healthy subjects, including 36 males and 34 females, aged 39 (25-57), were selected for methodology optimization. FCM was used to detect the ratio of marrow and circulating DLBCL cells in each group, and analyze the connection between circulating DLBCL cells and clinical indicators. Statistical analysis was performed using t test, χ 2 test, Kruskal-Wallis H test, Spearman rank correlation, and Logistic regression. Results:(1) Bone marrow and circulating DLBCL cells were not detected in CR group and control group; The positive rate of circulating DLBCL cells in the initial/recurrent group and PR groups was 75.47% and 57.14%, respectively. The proportion of bone marrow and circulating DLBCL cells was positively correlated in the two groups ( P value was <0.001 and 0.020, respectively). (2) The proportion of bone marrow and circulating DLBCL cells in the initial and recurrent groups, PR group, CR group and control group decreased successively ( P<0.05). The proportion of DLBCL cells was 27.72% (initial and recurrent bone marrow group), 26.92% (initial and recurrent circulating group), 3.23% (bone marrow PR group) and 1.67% (circulating PR group), respectively. (3) Compared with the negative group, the circulating DLBCL cell positive group had increased LDH, β 2-MG, and CMYC expression(≥80%), with decreased LYM, HGB<100 g/L, B symptoms, PD-L1 expression, and age ≥60 years, showing higher ECOG, aaIPI/IPI scores and Ann staging ( P<0.05). Age ≥60, B symptoms, and PD-L1 expression were independent risk factors for circulating DLBCL cells ( P<0.05). Conclusions:The detectable rate of circulating DLBCL cell could be improved by optimizing the preoperative treatment conditions of FCM. Circulating DLBCL cells can reflect the tumor burden and disease progression. Detecting circulating DLBCL cells may improve patients′ compliance.

HistonedemethylaseJMJD3promotesthestemnessofdiffuselargeBcelllymphoma cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effect of histone demethylase JMJD3 (jumonji domain-containing protein 3) on the stemness of diffuse large B-cell lymphoma (DLBCL) cells. Methods: The relationship between the expression of JMJD3 and the overall survival of DLBCL patients was analyzed using the clinical data of DLBCL patients in TCGA database. The control plasmid (pCMV) and JMJD3 expression plasmid(pCMV-JMJD3)weretransfectedintoDLBCLcellsofABCandGCBsubtype via lipofectamine transfection. Then, the mRNAlevels of JMJD3,ALDH1, OCT4 and SOX2 were detected by RT-PCR and qPCR; the activity ofALDH1 enzyme was detected by Flow cytometry; the protein expressions of OCT4 and SOX2 were detected by Western blotting. Gene enrichment in DLBCL patients with high JMJD3 expression was analyzed by gene set enrichment analysis (GSEA). Results: The result of prognosis analysis showed that high expression of JMJD3 was related with poor prognosis in DLBCL patients (P<0.05); however, multivariate analysis showed that the expression of JMJD3 was not the independent factor affecting the prognosis of DLBCL patients (all P>0.05). The expression of JMJD3 was remarkably increased in DLBCL cells transfected with pCMV-JMJD3, which led to significantly increased mRNA level and enzyme activity of ALDH1 as well as up-regulated mRNA and protein expressions of OCT4 and SOX2 (P<0.05 or P<0.01). GSEA analysis showed that enrichment of Wnt/β-catenin signaling pathway related gene set was observed in DLBCL patients with high JMJD3 expression (P<0.05). Conclusion: JMJD3 promotes the stemness of DLBCL cells, which may be a potential therapeutic target for DLBCL patients.

Classifying DLBCL according cell of origin using Hans algorithm and its association with clinicopathological parameters: A single centre experience

@#Introduction: In recent years, "double hit" and "double protein" involving gene rearrangement and protein expression of c-MYC and BCL2 and/or BCL6 are the most used terms to describe poor prognostic factors in diffuse large B-cell lymphoma (DLBCL). This study was to determine the frequency of double or triple protein expression by using immunohistochemistry (IHC) and comparing the result with clinicopathological features and cell of origin (COO) classification. Methods: We conducted a cross-sectional study by using 29 archived formalin-fixed paraffin embedded tissue blocks of DLBCL. All the samples were evaluated for the subgrouping of COO DLBCL was determined by expression of CD10, BCL6 and MUM1 based on Hans classification. In addition, expressions of c-MYC, BCL2 and BCL6 were detected by IHC. Results: Among the 29 cases, MYC, BCL2 and BCL6 proteins were detected in 72.4%, 62.1% and 62.1% of patients, respectively. Concurrent expression (c-MYC positive/BCL2 positive and/or BCL6 positive) was present in 58.6% of patients. 34.5% were categorised as germinal centre like (GCB) subgroup and 65.5% were categorised as nongerminal centre like (non-GCB) subgroup. Among the clinicopathological features, the double/triple protein expression lymphoma was significantly associated with elevated LDH level (p=0.018), IPI score (p=0.003), Ann Arbor stage (p=0.011) and complete response rate (p=0.011). Conclusion: Double/triple protein lymphoma was strongly associated more adverse clinical risk factors. Thus, analyses of MYC, BCL2 and BCL6 expression by IHC represents a rapid and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.

Curcumin Inhibits the Proliferation, Migration, Invasion, and Apoptosis of Diffuse Large B-Cell Lymphoma Cell Line by Regulating MiR-21/VHL Axis

Prognostic impact of MYD88 mutation, proliferative index and cell origin in diffuse large B cell lymphoma

Abstract Background Diffuse large B-cell lymphoma, among non-Hodgkin lymphomas, is one of the most frequent subtypes. Clinical laboratory data and post-treatment outcomes are scarce in the Brazilian population. Objective The main objective of this retrospective study was to assess the impact of tumor markers, including the Myeloid differentiation primary response 88 (MYD88) mutation. Method Eighty-three patients were included and treated with R-CHOP or R-CHOP-like regimens. Results Median age was 64-years old and 58% were female patients. The median follow-up was 42 months. The progression free survival (PFS) at this time was 63% and overall survival (OS), 66%. In the patients with tumors expressing Myc proto-oncogene protein (MYC) and B-cell lymphoma 2 (BCL2), assessed by immunohistochemistry (IHC), known as dual protein expressers, median post-progression survival was 31 (15-45) months. An increased proliferative index were associated with a high rate of progression (hazard ratio 2.31 [95% confidence interval [1.05-5.12]; p = 0.04). The cell of origin (COO), identified by IHC, was not able to predict PFS (p = 0.76). The MYD88 L265P mutation was present in 10.8% (9/83) of patients and did not show a prognostic correlation. Conclusion In conclusion, the MYD88 mutation, although an important tool for diagnosis and a possible target drug, presented at a low frequency and was not a prognostic marker in this population.

Clinical significance of cell-free DNA as a prognostic biomarker in patients with diffuse large B-cell lymphoma

BACKGROUND: Cell-free DNA (cfDNA) has the potential to serve as a non-invasive prognostic biomarker in some types of neoplasia. The investigation of plasma concentration of cfDNA may reveal its use as a valuable biomarker for risk stratification of diffuse large B-cell lymphoma (DLBCL). The present prognostic value of plasma cfDNA has not been widely confirmed in DLBCL subjects. Here, we evaluated cfDNA plasma concentration and assessed its potential prognostic value as an early DLBCL diagnostic tool. METHODS: cfDNA concentrations in plasma samples from 40 patients with DLBCL during diagnosis and of 38 normal controls were determined with quantitative polymerase chain reaction (qPCR) for the multi-locus L1PA2 gene. RESULTS: Statistically significant elevation in plasma cfDNA concentrations was observed in patients with DLBCL as compared to that in normal controls (P<0.05). A cutoff point of 2.071 ng/mL provided 82.5% sensitivity and 62.8% specificity and allowed successful discrimination of patients with DLBCL from normal controls (area under the curve=0.777; P=0.00003). Furthermore, patients with DLBCL showing higher concentrations of cfDNA had shorter overall survival (median, 9 mo; P=0.022) than those with lower cfDNA levels. In addition, elevated cfDNA concentration was significantly associated with age, B-symptoms, International Prognostic Index (IPI) score, and different stages of disease (all P<0.05). CONCLUSION: Quantification of cfDNA with qPCR at the time of diagnosis may allow identification of patients with high cfDNA concentration, which correlates with aggressive clinical outcomes and adverse prognosis.

pSTAT3 and MYC in Epstein-Barr virus-positive diffuse large B-cell lymphoma

@#Introduction: Epstein-Barr Virus (EBV) is associated with several B-cell non-Hodgkin’s lymphoma (NHL), but the role of EBV in diffuse large B-cell lymphoma (DLBCL) is poorly defined. Several studies indicated the expression of phosphorylated STAT3 (pSTAT3) is predominant in EBV(+)- DLBCL, of which its activated form can promote the downstream oncogenes expression such as c-MYC. c-MYC gene rearrangements are frequently found in aggressive lymphoma with inferior prognosis. Furthermore, EBV is a co-factor of MYC dysregulation. JAK1/STAT3 could be the downstream pathway of EBV and deregulates MYC. To confirm the involvement of EBV in JAK1/ STAT3 activation and MYC deregulation, association of EBV, pSTAT3 and MYC in EBV(+)- DLBCL cases were studied. The presence of pSTAT3 and its upstream proteins: pJAK1 is identify to delineate the role of EBV in JAK1/STAT3 pathway. Materials and Methods:51 cases of DLBCL paraffin-embedded tissue samples were retrieved from a single private hospital in Kuala Lumpur, Malaysia. EBER-ISH was performed to identify the EBV expression; ten EBV(+)-DLBCL cases subjected to immunohistochemistry for LMP1, pJAK1, pSTAT3 and MYC; FISH assay for c-MYC gene rearrangement. Results: Among 10 cases of EBV(+)-DLBCL, 90% were non-GCB subtype (p=0.011), 88.9% expressed LMP1. 40% EBV(+)-DLBCL had pJAK1 expression. Conclusion: 66.7% EBV(+)-DLBCL showed the positivity of pSTAT3, which implies the involvement of EBV in constitutive JAK/STAT pathway. 44.5% EBV(+)-DLBCL have co-expression of pSTAT3 and MYC, but all EBV(+)-DLBCL was absence with c-MYC gene rearrangement. The finding of clinical samples might shed lights to the lymphomagenesis of EBV associated with non-GCB subtypes, and the potential therapy for pSTAT3-mediated pathway.

Advances in targeted drug therapy for relapse/refractory diffuse large B-cell lymphoma / 中国肿瘤临床

Lymphoma is a group of heterogeneous hematological malignant tumors originating from lymph nodes or other lymphoid tissues, including Hodgkin's lymphoma and non-Hodgkin's lymphoma. Diffuse large B-cell lymphoma (DLBCL) is one of the most com-mon subtypes of non-Hodgkin's lymphoma (NHL) with obvious heterogeneity. Standard R-CHOP regimen (rituximab combined with cy-clophosphamide, adriamycin, vincristine and prednisone) can significantly improve the survival of more than 60% of patients. Howev-er, there are still about 30%-40% of patients with relapse or refractory disease, and the prognosis is very poor. How to prolong the sur-vival of relapsed/refractory DLBCL patients and improve their prognosis has become a research hotspot. With the continuous in-depth study of gene expression profiles and molecular mechanisms of drug resistance, new chemotherapy schemes and new drugs emerge, which brings new hope for individualized precise treatment of relapsed/refractory DLBCL. This article reviews the recent progress of targeted drugs in the treatment of relapsed/refractory DLBCL.

The prognostic value of prognostic nutritional index in patients with diffuse large B-cell lymphoma / 中国肿瘤临床

Objective: To investigate the prognostic value of prognostic nutritional index (PNI) in patients with diffuse large B-cell lym-phoma (DLBCL). Methods: We retrospectively reviewed the medical records of 82 patients with DLBCL treated at Tianjin Union Medi-cal Center between June 2010 and June 2016. The optimal cutoff value of PNI was determined using a receiver operating characteristic (ROC) curve and the Youden index. The relationship of high and low PNI with the clinical characteristics of the patients, therapeutic ef-ficacy, and prognosis were analyzed. Results: Overall, mean PNI of the patients was 46.17±8.8. When the PNI was 44.15, the Youden in-dex was found to be maximal, with a sensitivity of 74.6% and specificity of 67.2%. There were 38 patients (46.3%) in the low PNI group (<44.15) and 44 patients (53.7%) in the high PNI group (≥44.15). Data analysis showed that PNI was correlated with Eastern Coopera-tive Oncology Group performance status (ECOG PS), Ann Arbor stage, international prognostic index (IPI) score, and lactic acid dehydro-genase (LDH) level (P<0.05). The total effective rate of the low PNI group was significantly lower than that of the high PNI group (65.8% vs. 86.4%; χ2=4.848; P=0.028). The 3-year overall survival (OS) rate of the entire group of patients was 69.1%. The 1-, 2-, and 3-year OS rates of the low PNI group (86.8%, 67.8%, and 56.9%, respectively) were significantly lower than that of the high PNI group (96.7%, 89.5%, and 80.2%, respectively; χ2=9.421, P=0.002). Univariate analysis showed that PNI<44.15, ECOG PS≥2, IPI>2, stageⅢ/Ⅳ, and lymphocyte count<1.0×109/L had a significant impact on predicting OS (P<0.05). Multivariate analysis showed that PNI<44.15 (P=0.006) and stageⅢ/Ⅳ(P=0.011) were independent factors for predicting OS. Conclusions: PNI might be used as a simple and feasible clinical prognostic indicator in patients with DLBCL.

Clinical impacts of inflammatory markers and clinical factors in patients with relapsed or refractory diffuse large B-cell lymphoma

BACKGROUND: Systemic inflammatory response can be associated with the prognosis of diffuse large B cell lymphoma (DLBCL). We investigated the systemic factors significantly related to clinical outcome in relapsed/refractory DLBCL.METHODS: In 242 patients with DLBCL, several factors, including inflammatory markers were analyzed. We assessed for the correlation between the survivals [progression-free survival (PFS) and overall survival (OS)] and prognostic factors.RESULTS: In these patients, a high derived neutrophil/lymphocyte ratio (dNLR) (PFS, HR=2.452, P=0.002; OS, HR=2.542, P=0.005), high Glasgow Prognostic Score (GPS) (PFS, HR=2.435, P=0.002; OS, HR=2.621, P=0.002), and high NCCN-IPI (PFS, HR=2.836, P=0.003; OS, HR=2.928, P=0.003) were significantly associated with survival in multivariate analysis. Moreover, we proposed a risk stratification model based on dNLR, GPS, and NCCN-IPI, thereby distributing patients into 4 risk groups. There were significant differences in survival among the 4 risk groups (PFS, P<0.001; OS, P<0.001).CONCLUSION: In conclusion, dNLR, GPS, and NCCN-IPI appear to be excellent prognostic parameters for survival in relapsed/refractory DLBCL.

Correlation between D-loop SNPs of mitochondrial DNA and diffuse large B cell lymphoma / 中国肿瘤生物治疗杂志

@# Objective: To investigate the correlations between single nucleotide polymorphisms (SNPs) in the D-loop of mitochondrial DNA (mtDNA) and the disease risk as well as the prognosis of diffuse large B cell lymphoma (DLBCL). Methods: Blood samples from 108 DLBCL patients treated at the Department of Hematology of the Fourth Hospital of Heibei Medical University during July, 1991 and July 2012 were collected for this study; in addition, blood samples from 159 healthy controls during the same period were also collected. DNA was extracted according to the standard protocols for PCR amplification and SNP locus genotype analyses. The risk of D-loop SNPs was investigated by case-control study. Results: The minor alleles of nucleotides 73A/G, 263A/G, 315C/C insert were associated with a decreased risk for DLBCL. The minor allele of the nucleotides 200G/Awas associated with an increased risk for DLBCL. To further evaluate the predictive function of D-loop SNPs in DLBCL patients, five SNP sites were identified by Log-Rank test that with statistically significant prediction value of DLBCL survival in a univariate analysis. In a multivariate analysis, allele 16304 was identified as an independent predictor of DLBCL prognosis. The survival time of DLBCL patients with 16304C was significantly shorter than that of patients with 16304T (RR=0.513, 95% CI=0.266-0.989, P<0.05). Conclusion: The analysis of D-loop SNPs in mtDNA can help identifying the occurrence risks and poor prognosis subtypes of DLBCL.

Prognostic evaluation of different PET/CT reading methods in Hodgkin lymphoma and diffused large B-cell lymphoma / 上海交通大学学报（医学版）

18F-fluoro-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has been used as a crucial imaging modality for staging and prognosis evaluation in the patients with lymphoma. Since biological characteristics, treatment responses and prognosis vary in different subtypes of lymphoma, this review mainly focused on progress of 18F-FDG PET/CT evaluation in prognosis of Hodgkin lymphoma (HL) and diffused large B-cell lymphoma (DLBCL). The significance in prognostic evaluation of interim 18F-FDG PET/CT in HL is well-known, but it still remains controversy in DLBCL. Moreover, the semi-quantitative method of 18F-FDG PET/CT evaluation in lymphoma has bright future.

Primary breast diffuse large B-cell lymphoma: a report of 21 cases / 中国肿瘤临床

Objective: To investigate the clinical characteristics, treatment regimens, and outcomes of patients with primary breast dif-fuse large B-cell lymphoma (PB-DLBCL). Methods: Between January 2010 and January 2018, 21 patients with PB-DLBCL were diag-nosed, treated, and followed up at the First Affiliated Hospital of Zhengzhou University. All patients were female, with a median age of 49 years (ranging from 21 to 77 years) at presentation. All patients received chemotherapy, of which 17 patients received the CHOP regimen and 4 received the EPOCH regimen. Eight patients received chemotherapy followed by radiotherapy, and 13 received chemo-therapy alone. Six patients received prophylactic intrathecal injections. The incidences of refractory and progressive disease between patients who received different regimens were analyzed using the Chi-square test. The overall survival (OS) and progression-free sur-vival (PFS) rates were calculated using the Kaplan-Meier method, and differences in survival were compared using the Log-rank test. Multivariate analysis was performed with the Cox-regression model for those factors that were confirmed as significant in the univari-ate analysis. Results: The most common presentation was a painless mass. The 5-year OS and PFS rates were 74% and 66%, respective-ly. There was no significant difference in the incidence of refractory or progressive disease between the EPOCH and CHOP groups (P=0.603). Six of those who received prophylactic intrathecal injections had no central nervous system recurrence, and 2 patients who did not receive prophylactic intrathecal injections had central nervous system recurrence. Univariate and multivariate analyses showed that both the level of serum β2 microglobulin [P=0.044, hazard ratio (HR)=0.431, 95% confidence interval (CI): 0.432-0.967] and radio-therapy (P=0.002, HR=0.495, 95% CI: 1.073-2.508) were related to the OS of PB-DLBCL. Conclusions: PB-DLBCL often occurs in women, mostly involving the unilateral breast, which manifests mainly as a painless mass. The level of serum β2 microglobulin is a factor of poor prognosis in PB-DLBCL. The treatment modality of chemotherapy combined with radiotherapy can significantly improve the OS of PB-DLBCL. Prophylactic intrathecal injections may be useful to reduce the incidence of refractory disease or recurrence in the central nervous system.

Clinical significance of changes in levels of serum β2-MG, VEGF, and LDH in patients with diffuse large B-cell lymphoma after treatment / 中国肿瘤临床

Objective: To assess the clinical significance of changes in levels of serum β2 microglobulin (β2-MG), vascular endothelial growth factor (VEGF), and lactate dehydrogenase (LDH) in patients with diffuse large B-cell lymphoma (DLBCL) after treatment. Methods: A total of 89 patients with DLBCL who were admitted to the hospital between February 2015 an July 2017 were included in the DLBCL group and 40 normal, healthy persons admitted during the same period were selected as the control group. All DLBCL patients underwent standard chemotherapy after admission. Peripheral venous blood was collected before and after chemotherapy to determine any changes in serum β2-MG, VEGF, and LDH levels. Biomarker levels were also compared with those from normal, healthy subjects. The clinical and pathological data of all DLBCL patients were collected and the relationships between changes in biomarker levels, clinical and pathological parameters of DLBCL, and curative effects were analyzed. Results: The levels of serum β2-MG, VEGF, and LDH in the DLBCL group were higher than those in the control group (P<0.05) and all levels in DLBCL group decreased after chemotherapy (P<0.05). The effective rate of the R-CHOP group was higher than that of the CHOP group (P<0.05). Serum LDH levels were higher in patients with typical B symptoms than in those without such symptoms (P<0.05). Serum levels of β2-MG, VEGF, and LDH were higher in patients with Ann Arbor stageⅢ-Ⅳlymphoma, with bone marrow involvement, whose international prognostic index (IPI) was high-risk, and with treatment failure than in those with stageⅠ-Ⅱlymphoma, without bone marrow involvement, with low-risk IPI, and with treatment response (P<0.05). The levels of serum VEGF, β2-MG, and LDH were positively correlated with each other, and all three biomarkers were negatively correlated with treatment response (P<0.05). Conclusions: Levels of serum β2-MG, VEGF, and LDH are elevated in patients with DLBCL but are significantly decreased after treatment. Changes in expression levels of these three biomarkers are related to clinical stage, bone marrow involvement, IPI, and treatment response. These biomarkers can be used as a basis for monitoring DLBCL and evaluating curative effect and prognosis.

Progress in research on prognosis-related gene mutations in diffuse large B-cell lym-phoma through next generation sequencing / 中国肿瘤临床

Diffuse large B-cell lymphoma(DLBCL)is a highly invasive malignant lymphoma,and the molecular mechanism of its patho-genesis is not fully understood.Next generation sequencing(NGS)is an increasingly mature gene assay technology,which has been widely applied in recent years to study the genetics of DLBCL.Targeted therapy development has progressed significantly on the basis of these studies,which has made genetic mutations in DLBCL become the new research hotspot.This review summarizes the progress in research on progress-related gene mutations in DLBCL.