Functions of N6-methyladenosine (m6A) RNA modifications in acute myeloid leukemia.

N6-methyladenosine (m6A) is the most common modification of eukaryotic RNA. m6A participates in RNA splicing, nuclear export, translation, and degradation through regulation by methyltransferases, methylation readers, and demethylases, affecting mRNA stability and translation efficiency. Through the dynamic and reversible regulatory network composed of " Writers-Erasers-Readers", m6A modification plays a unique role in the process of hematopoiesis. Acute myeloid leukemia (AML) is a heterogeneous disease characterized by malignant proliferation of hematopoietic stem cells/progenitor cells. Many studies have shown that m6A-related proteins are abnormally expressed in AML and play an important role in the occurrence and development of AML, acting as carcinogenic or anticancer factors. Here, we describe the mechanisms of action of reversing m6A modification in hematopoiesis and AML occurrence and progression to provide a basis for further research on the role of m6A methylation and its regulatory factors in normal hematopoiesis and AML, to ultimately estimate its potential clinical value.

Efficacy of Surgery in Patients with Stage I Primary Parotid Gland Lymphoma: A Population-Based Study.

Background: Limited and controversial evidence is available on the efficacy of surgery for patients with stage I primary parotid gland lymphoma. Thus, we aimed to investigate whether surgery can enhance the prognosis of patients with stage I primary parotid gland lymphoma using large sample data. Methods: From 1998 to 2015, we searched the Surveillance, Epidemiology, and End Results (SEER) program database and extracted information regarding patients with stage I primary parotid gland lymphoma; we classified these patients into surgery and nonsurgery groups. We calculated overall survival (OS) and cancer-specific survival (CSS) using Kaplan-Meier curves and log-rank testing. Propensity score matching (PSM) analysis was also used to further account for confounding variables before comparing the OS and CSS again. We used the COX proportional hazard regression model in both multivariate and univariate analyses. Results: We enrolled 918 patients with stage I primary parotid gland lymphoma, among which 656 (71.5%) patients underwent surgery. Before PSM, the surgery group had better OS (hazard ratio (HR) = 0.673, 95% confidence interval (CI): 0.519-0.873, and p=0.003) and CSS (HR = 0.595, 95% CI: 0.403-0.879, and p=0.008) than the nonsurgery group. After PSM, surgery was still a beneficial factor for OS (HR = 0.569, 95% CI: 0.399-0.810, and p=0.002) and CSS (HR = 0.384, 95% CI: 0.220-0.669, and p=0.001). Furthermore, in univariate and multivariate analyses, total parotidectomy significantly increased OS (p=0.001 and p=0.021, respectively) and CSS (p=0.001 and p=0.037, respectively). Conclusions: In summary, the prognosis of patients with stage I primary parotid gland lymphoma can be significantly improved by surgery. Moreover, total parotidectomy was a protective factor for OS and CSS before and after PSM analysis, suggesting that surgery acts as a significant component in multimodal therapy for early primary parotid gland lymphoma.

A bibliometric analysis of CD38-targeting antibody therapy in multiple myeloma from 1985 to 2021.

Background: CD38 is a transmembrane glycoprotein that is relatively highly expressed on multiple myeloma (MM) cells, and CD38-targeting antibodies use pleiotropic mechanisms to kill MM cells. Immunotherapy, with an increased quality of response and acceptable toxicity, shows tremendous potential for treating MM. This research field study aimed to analyze all the relevant literature via bibliometrics to identify its course of development and structural relationships. Methods: A total of 1,030 relevant articles were retrieved from the Web of Science Core Collection (WoSCC) from 1985 to June 21, 2021. CiteSpace was employed to map authors/references/countries with nodes and links, extract highly cited keywords, analyze the time trends of keywords, recognize cocited authors/references, set timezone or timeline views, analyze burstness and generate a dual map. VOSviewer was used to recognize connections among journals and construct collaboration networks. bibliometric.com was utilized to trace advanced countries/regions in the research field. Results: All of the articles were cited 24,332 times in total, with an average of 23.62 times. Most articles were published in the United States of America (USA), far outweighing other countries/regions. The current hotspots in this field are related to the following keywords: "monoclonal antibody", "refractory MM", "idecabtagene vicleucel", and "B cell maturation antigen (BCMA)". Ten significant clusters, namely, "flow cytometry", "daratumumab", "BCMA", "cell line", "antitumor activity", "gene", "non-Hodgkin's lymphoma", "peripheral blood", "survival" and "anti-CD38", were extracted. The mechanism and effectiveness of CD38-targeting antibodies in treating MM have been studied. Future research hotspots will focus on new therapies for relapsed and refractory multiple myeloma (RRMM) patients. Conclusions: In the past, efforts were applied to elucidate the mechanism and effectiveness of CD38-targeting antibodies in treating MM. Future research hotspots will focus on anti-BCMA chimeric antigen receptor T cell (CAR-T) immunotherapy for patients with RRMM. According to this article, new researchers can discover its course of development and structural relationships in this field.

CAR-T cell therapy targeting B cell maturation antigen is effective for relapsed/refractory multiple myeloma, including cases with poor performance status.

In this open-label, single-arm, phase I/II clinical trial, we evaluated the efficacy of anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell (HDS269B) therapy in 49 relapsed/refractory multiple myeloma (RRMM) patients, including 20 with Eastern Cooperative Oncology Group (ECOG) grade 3-4. After HDS269B infusion (9 × 106 CAR+ cells/kg), 17 patients (34.69%, 11 ECOG 0-2, 6 ECOG 3-4) developed cytokine release syndrome [grade 1-2: 14 patients (28.57%); grade 3: 3 patients (6.12%)]. The objective response rate (ORR) was 77%, with a complete response (CR) achieved in 47%. Ongoing response >12 months occurred in 15 patients, and was extended beyond 38 months in one patient. The median progression-free survival (PFS) and overall survival (OS) were 10 months (95% CI 5.3-14.7) and 29 months (95% CI 10.0-48.0), respectively. The PFS (12 months) and OS (18 months) rates were 41.64% and 62.76%, respectively. In patients with ECOG 0-2 and 3-4, ORR was 79.31% (23/29) and 75.0% (15/20) and PFS were 15 months (95% CI 5.4-24.6) and 4 months (95% CI 0-11.7), respectively. OS was not reached in ECOG 0-2 patients, but was 10.5 months (95% CI 0-22) in ECOG 3-4 patients. Single-cell sequencing indicated that treatment efficacy might be related to mTORC1 signaling. Thus, HDS269B therapy is safe and effective for RRMM patients, even those with ECOG 3-4.

[Toxicity Management and Efficacy Evaluation of BCMA-CART in the Treatment of Relapsed and Refractory Multiple Myeloma].

OBJECTIVE: To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM). METHODS: The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated. RESULTS: After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity. CONCLUSION: BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.