BET bromodomain inhibitors PFI-1 and CPI-203 suppress the development of follicular lymphoma via regulating Wnt/ß-catenin signaling.

Objective: Follicular lymphoma (FL) is an indolent B-cell lymphoproliferative disorder, characterized by a lymphoid follicular pattern of growth. PFI-1 or CPI-203 has been known to effectively promote the inhibition of primary effusion lymphoma progression. This study aimed at investigating the anti-tumor properties of PFI-1 and CPI-203 on FL cells and uncover the underlying mechanism of action. Methods: FL cells were treated with PFI-1 and CPI-203, and the treated cells were evaluated for their cell viability, cell cycle and apoptosis using CCK8, flow cytometry, and Western blot assays. A xenograft mouse model was used for assessing the in vivo effects of CPI-203 on tumorigenesis. Results: PFI-1 or CPI-203 showed potential inhibitory effects on the cell viability of DOHH2 and RL cells in a dose-response-dependent manner. Furthermore, PFI-1 and CPI-203 inhibited cell growth, induced apoptosis of FL cells in vitro, and facilitated the translocation of ß-catenin into cytoplasm both in vitro and in vivo. After engrafted with FL cells, CPI-203-treated mice got a longer duration of survival and a smaller tumor size than control mice. Mechanistically, PFI-1 and CPI-203 impede the activity of ß-catenin and its downstream molecules by regulating the DVL2/GSK3ß axis. Conclusion: In conclusion, PFI-1 and CPI-203 may serve as potential anti-tumor inhibitors for the therapy of FL.

[Clinical Characteristics and Correlation with Prognosis of DLBCL with Bone Marrow Involvement and Chromosomal Abnormalities].

OBJECTIVE: To investigate the clinical characteristics of diffuse large B-cell lymphoma(DLBCL) patients with bone marrow involvement and chromosome abnormalities, and further analyze the correlation between the degree of chromosome abnormality and prognosis. METHODS: The clinical data of 88 patients diagnosed with DLBCL with bone marrow involvement and complete chromosomal findings in Shanxi Province Cancer Hospital were retrospectively analyzed. The χ2 test was used to analyze their clinical characteristics, and the Kaplan-Meier method was used in PFS and OS, and log-rank method in comparison. RESULTS: Chromosome abnormalities were detected in 31 of the 88 patients(35.2%), 15 of whom had complex karyotype(17.0%). The positive rate of BCL-2, BCL-6, C-MYC and Ki-67≥80% was high in patients with complex karyotype, and most of them are double expressor lymphoma. Survival analysis showed that patients with complex karyotype of DLBCL had poorer PFS and OS compared to those with normal karyotype and 1-2 chromosomal abnormalities. CONCLUSION: In DLBCL patients with bone marrow involvement and chromosome abnormalities, patients with complex karyotype have a shorter survival time.

The prognostic index PRIMA-PI combined with Ki67 as a better predictor of progression of disease within 24 months in follicular lymphoma.

Background: Progression of disease within 24 months (POD24) is a risk factor for poor survival in follicular lymphoma (FL), and there is currently no optimal prognostic model to accurately predict patients with early disease progression. How to combine traditional prognostic models with new indicators to establish a new prediction system, to predict the early progression of FL patients more accurately is a future research direction. Methods: This study retrospectively analyzed patients with newly diagnosed FL patients in Shanxi Provincial Cancer Hospital from January 2015 to December 2020. Data from patients undergoing immunohistochemical detection (IHC) were analyzed using χ2 test and multivariate Logistic regression. Also, we built a nomogram model based on the results of LASSO regression analysis of POD24, which was validated in both the training set and validation set, and additional external validation was performed using a dataset (n = 74) from another center, Tianjin Cancer Hospital. Results: The multivariate Logistic regression results suggest that high-risk PRIMA-PI group, Ki-67 high expression represent risk factors for POD24 (P<0.05). Next, PRIMA-PI and Ki67 were combined to build a new model, namely, PRIMA-PIC to reclassify high and low-risk groups. The result showed that the new clinical prediction model constructed by PRIMA-PI with ki67 has a high sensitivity to the prediction of POD24. Compared to PRIMA-PI, PRIMA-PIC also has better discrimination in predicting patient's progression-free survival (PFS) and overall survival (OS). In addition, we built nomogram models based on the results of LASSO regression (histological grading, NK cell percentage, PRIMA-PIC risk group) in the training set, which were validated using internal validation set and external validation set, we found that C-index and calibration curve showed good performance. Conclusion: As such, the new predictive model-based nomogram established by PRIMA-PI and Ki67 could well predict the risk of POD24 in FL patients, which boasts clinical practical value.

ALK-Positive Anaplastic Large-Cell Lymphoma in a Patient with Chronic Lymphocytic Leukemia: A Case Report and Literature Review.

Chronic lymphocytic leukemia (CLL) can experience histological transformation to a more aggressive lymphoma called "Richter's transformation". This transformation usually leads to diffuse large B cell lymphoma, though cases of T cell lymphoma have been identified. Here we report an extremely rare case of ALK (anaplastic lymphoma kinase) positive anaplastic large cell lymphoma. We performed detailed examination for this patient and reviewed related literatures to understand the transformation. Despite our best effort, this patient passed away shortly. Literature review shows no consensus on treatment and poor prognosis of this condition. We intend to report this case and explore novel treatment possibilities for these patients.

Chidamide induces apoptosis in DLBCL cells by suppressing the HDACs/STAT3/Bcl­2 pathway.

Diffuse large B­cell lymphoma (DLBCL) is a highly heterogeneous malignant tumor type, and epigenetic modifications such as acetylation or deacetylation serve vital roles in its development. Chidamide, a novel histone deacetylase inhibitor, exerts an anticancer effect against various types of cancer. The present study aimed to evaluate the cellular effect of chidamide on a number of DLBCL cell lines and to investigate its underlying mechanism. The results demonstrated that chidamide induced the death of these cells in a concentration­(0­30 µmol/l) and time­dependent (24­72 h) manner, as determined using the Cell Counting Kit­8 cell viability assay. Moreover, chidamide promoted cellular apoptosis, which was identified via flow cytometry and western blot analysis, with an increase in cleaved caspase­3 expression and a decrease in Bcl­2 expression. Chidamide treatment also decreased the expression level of STAT3 and its phosphorylation, which was accompanied by the downregulation of a class­I histone deacetylase (HDAC) inhibitor, chidamide. Collectively, these data suggested that chidamide can be a potent therapeutic agent to treat DLBCL by inducing the apoptotic death of DLBCL cells by inhibiting the HDACs/STAT3/Bcl­2 pathway.

Primary Gastric Diffuse Large B-Cell Lymphoma: Prognostic Factors in the Immuno-Oncology Therapeutics Era

Objective: This study aimed to explore the prognostic factors for primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Materials and Methods: This retrospective study analyzed 72 PG-DLBCL patients between January 2012 and December 2017 in the Shanxi Cancer Hospital of Shanxi Medical University to identify the different prognostic factors in PG-DLBCL. The clinical features, treatment, and follow-up information were analyzed. Results: The low CD4:CD8 ratio group (median subsequent overall survival [OS]: 36.06 months; 95% confidence interval [CI]: 25.73-46.40) showed a significant decrease in subsequent OS compared to the normal group among PG-DLBCL patients who were newly diagnosed and did not receive rituximab (median OS: 52.58 months; 95% CI: 44.18-60.97; p=0.029). Event-free survival status 24 months after the date of diagnosis (EFS24) also decreased significantly in the low CD4:CD8 group (median EFS24: 16.27 months; 95% CI: 13.09-19.45) compared to the normal group (median EFS24: 20.34 months; 95% CI: 17.05-23.63; p=0.014). Multivariate analysis showed that low CD4:CD8 at diagnosis was an independent poor prognostic factor for subsequent OS and EFS24. Conclusion: Our data suggest that identifying prognostic factors, especially host immunity, may provide useful information for assessing prognosis or clinical management.

Primary hematological malignancy of the uterine cervix: A case report.

The present case report investigated the clinical characteristics of primary hematological malignancy of the uterine cervixin five patients. Among the five patients, three patients were diagnosed with non-Hodgkin's lymphoma (NHL) and two patients with myeloid sarcoma (MS) of the uterine cervix. Biopsies of the uterine cervices demonstrated the involvement of lymphoid cells or myeloid blasts cells. Immunohistochemical staining demonstrated the expression of B-lymphoid and myeloid lineage markers. The associated lysozyme, myeloperoxidase and mast/stem cell growth factor receptor (CD117) markers were specific for the diagnosis of MS. The three patients with NHL survived, and one of the patients survived for 82 months with no evidence of disease; however, was eventually lost to follow-up. The two patients with MS succumbed to the cancer as a result of progressive disease and leukemia. Therefore, pathological examination may be important for the timely diagnosis and appropriate therapeutic regimen for primary hematological malignancy of the uterine cervix.

Autologous peripheral blood stem cell transplantation in children and adolescents with non-Hodgkin lymphoma.

The aim of this study was to evaluate the effect and safety of autologous peripheral blood stem cell transplantation (APBSCT) in children and adolescents with non-Hodgkin lymphoma (NHL). Ten patients with NHL were analyzed retrospectively. In all the patients, lymph node enlargement was most frequently detected. Patients with a mediastinal mass presented with a cough, palpitation and shortness of breath. Extranodal patients presented with abdominal pain, inability to walk and vaginal bleeding. All patients underwent APBSCT with conditioning regimens BEAM or BuCy. Among them, four patients with B-cell NHL received rituximab in addition to the conditioning regimen. Hematopoietic reconstitution was observed in all patients. Severe toxicity and transplant-related mortality were not observed. Prior to APBSCT, nine patients with a status of complete response (CR) and CR unconfirmed achieved continuing complete remission. Only one patient with partial response succumbed to progressive disease. APBSCT in children and adolescents with NHL is a safe, convenient and efficient treatment. The BEAM conditioning regimen was shown to be effective and tolerable for children and adolescents with NHL. Rituximab is a safe agent in the transplantation. The CR status at the time of transplantation demonstrated a higher survival rate.

[Clinical detection of CMV in allogeneic bone marrow transplantation--review].

Human cytomegalovirus (CMV) infection may cause life-threatening complications and lead to failure in transplantation. So, it is very important to explore the laboratory methods which can detect the CMV sufficiently early and accurately. This review discusses methodological aspects of quantitative CMV assays with emphasis on recently developed antigen detection assays and molecular biological methods.