The patients with multiple myeloma were infected with COVID-19 during autologous stem cell transplantation: case report and literature review.

This paper introduces two cases of multiple myeloma, COVID-19 infection during autologous stem cell transplantation, the treatment process, and different results of the two patients, which provides a reference for how to carry out ASCT safely during the COVID-19 normalization stage.

Increased coexpression of PD-L1 and IDO1 is associated with poor overall survival in patients with NK/T-cell lymphoma.

Immunotherapy with programmed cell death 1 ligand 1 (PD-L1) blockade was effective in patients with NK/T-cell lymphoma. In addition to PD-L1, indoleamine 2,3-dioxygenase-1 (IDO1) is one of the most promising immunotherapeutic targets. High proportions of PD-L1 and IDO1 proteins were observed by immunohistochemistry (IHC) from 230 newly diagnosed patients with NK/T lymphoma with tissue samples from three cancer centers and were associated with poor overall survival (OS) in patients with NK/T lymphoma. Importantly, the coexpression of PD-L1 and IDO1 was related to poor OS and short restricted mean survival time in patients with NK/T lymphoma and was an independent prognostic factor in the training cohorts, and which was also validated in 58 NK/T lymphoma patients (GSE90597). Moreover, a nomogram model constructed with PD-L1 and IDO1 expression together with age could provide concise and precise predictions of OS rates and median survival time. The high-risk group in the nomogram model had a positive correlation with CD4 + T-cell infiltration in the validation cohort, as did the immunosuppressive factor level. Therefore, high PD-L1 and IDO1 expression was associated with poor OS in patients with NK/T lymphoma. PD-L1 and IDO1 might be potential targets for future immune checkpoint blockade (ICB) therapy for NK/T lymphoma.

High-dose methotrexate, thiotepa, orelabrutinib combined with or without rituximab in primary or secondary central nervous system diffuse large B-cell lymphoma: a single-center retrospective analysis.

Purpose: Central nervous system lymphoma (CNSL) is an aggressive non-Hodgkin's lymphoma (NHL) confined to the central nervous system (CNS). Orelabrutinib is an oral second-generation Bruton tyrosine kinase (BTK) inhibitor and a novel therapeutic strategy for CNSL. The purpose of this study was to evaluate the effectiveness and safety of high-dose methotrexate (HD-MTX), thiotepa, and orelabrutinib combined with or without rituximab (MTO±R)regimen in the treatment of patients with CNSL. Methods: A total of 14 patients with CNS diffuse large B-cell lymphoma (DLBCL) were included in this retrospective study. All patients received the regimen MTO±R. Overall response rate (ORR), complete response rate(CR), partial response (PR), stable disease (SD), progressive disease (PD), progression-free survival (PFS), overall survival (OS), and the safety of MTO±R were assessed by the investigator. Results: Fourteen patients were evaluable for safety, and 13 patients were evaluable for efficacy. The overall CR rate was 69.2%, and the ORR was 92.3% for total patients. For PCNSL, the CR rate and ORR were 55.6% and 88.9%, respectively. For relapsed/refractory CNSL, the CR rate and ORR were 66.7% and 91.7%, respectively. The median follow-up time was 12.8 months. The median PFS was 11.3 months, and the median OS was not achieved. The 12-month PFS and OS rates were 60% and 70%, respectively. Adverse events occurred in 17 cycles, and Grade 3 AEs occurred in 5 patients (35.7%). Conclusion: MTO±R was an efficacious and well-tolerated regimen in patients with CNSL. A novel BTK inhibitor in combination with chemotherapy offers a new potential therapeutic strategy for patients with CNSL.

Current status and future prospects of chimeric antigen receptor-T cell therapy in lymphoma research: A bibliometric analysis.

CAR-T cell therapy, a novel therapeutic approach that has attracted much attention in the field of cancer treatment at present, has become the subject of many studies and has shown great potential in the treatment of hematological malignancies, such as leukemia and lymphoma. This study aims to analyze the characteristics of articles published on CAR-T cell therapy in the lymphoma field and explore the existing hotspots and frontiers. The relevant articles published from 2013 to 2022 were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, Bibliometric online analysis platform, Microsoft Excel, and R software were used for bibliometric analysis and visualization. The number of publications related to the research has been increasing year by year, including 1023 articles and 760 reviews from 62 countries and regions, 2092 institutions, 1040 journals, and 8727 authors. The United States, China, and Germany are the main publishing countries in this research field. The top 10 institutions are all from the United States, the journal with the highest impact factor is BLOOD, the author with the most publications is Frederick L Locke, and the most influential author is Carl H June. The top three keywords are "Lymphoma," "Immunotherapy," and "Therapy." "Maude (2014)" is the most cited and strongest burstiness reference over the past decade. This study provides a comprehensive bibliometric analysis of CAR-T cell therapy in lymphoma, which can help researchers understand the current research hotspots in this field, explore potential research directions, and identify future development trends.

Involvement of spleen is associated with shorter survival in patients with angioimmunoblastic T cell lymphoma.

BACKGROUND: The prognosis of patients with angioimmunoblastic T cell lymphoma (AITL) remains dismal, with their 5-year overall survival (OS) and progression-free survival (PFS) rates of 32-41% and 18-38%, respectively. Spleen involvement occurs in a proportion of patients with AITL. But still, it is unclear whether spleen involvement impacts the prognosis of AITL patients. In this study, we aim to establish new prognostic indicators for the identification of high-risk patients to draft optimal treatment regimens. METHODS: We collected and counted the clinical data of 54 patients with AITL treated with CHOP-based first-line chemotherapy regimen between 2010 and 2021 at Hubei Cancer Hospital and Hunan Cancer Hospital. In addition, all patients received PET-CT scan prior to receiving treatment. We performed univariate and multivariate analyses to assess the predictive role of tumor characteristics, laboratory, and radiographic data for the prognosis of AITL. RESULTS: We observed that PFS and OS are worse in patients with high ECOG scores, spleen involvement, and low serum albumin levels in patients with AITL. In univariate analysis, stage (HR 3.515 [1.142-10.822], p = 0.028) and spleen involvement (HR 8.378 [1.085-64.696, p = 0.042) were correlated with PFS in patients with AITL. Besides, stage (HR 3.439 [1.108-10.674], p = 0.033) and spleen involvement (HR 11.002 [1.420-85.254], p = 0.022) were significantly correlated with OS. Consistently, spleen involvement was correlated with OS (HR 16.571 [1.350-203.446], p = 0.028) and PFS (HR 10.905 [1.037-114.690], p = 0.047) in AITL patients in a multivariate analysis. CONCLUSION: This study demonstrates that spleen involvement might be used as a prognostic indicator for AITL patients.

Global Research Trends on the Treatment of Diffuse Large B-Cell Lymphoma: A Bibliometric and Visualized Study.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype. Treatment of DLBCL has improved greatly in recent decades, with thousands of papers published. We conducted a bibliometric analysis of the literature on DLBCL treatment, and discussed cooperation among authors, countries, and institutions, and identified research hotspots for DLBCL treatment. We searched the Web of Science Core Collection (WOSCC) using "Diffuse Large B Cell Lymphoma or DLBCL" and "Treatment or Therapy or Clinical Trial" as the subject terms, and analyzed the publication year, research direction, country/region, institution, author, source publication, distribution of funding institutions, and other conditions provided by the database. In addition, scientometrics software was used to analyze literature citations and cooperative publications. Bibliometric analyses were performed using https://bibliometric.com/app and VOSviewer. Network maps were generated to evaluate collaborations between different authors, countries, institutions, and keywords. A total of 7,255 studies on treatment of DLBCL were retrieved from the WOSCC on February 19, 2021. We found that the number of publications increased gradually from 1999 to 2021, and this trend was relatively stable in the past 3 years. The countries that produced the most publications were the United States, China, and Japan. Among institutions, University of Texas MD Anderson Cancer Center published the most manuscripts. Furthermore, the United States also had the most annual publications, citations, distribution of journal sources, and funding. Cooperative research between countries is also relatively important to treatment of DLBCL. Therapeutic regimens such as CHOP and R-CHOP, and immunotherapy (CAR-T, PD1/PDL1, and CAR-NK, etc.), have received increased attention. Bibliometric analysis of studies related to DLBCL treatment can help researchers and clinical workers quickly understand the hotspots and development trends in this field, and provide reference for the formulation of public health policies.

Successful Treatment of Primary CNS Extranodal NK/T-Cell Lymphoma with Surgery and Chemotherapy Combined with Sintilimab: A Case Report and Literature Review.

Primary central nervous system extranodal natural killer/T-cell lymphoma (PCNS ENK/TCL) is an extremely rare lymphoma. Only 23 cases of PCNS ENK/TCL have been reported in the English literature. Due to the rarity of this lymphoma, an effective therapeutic strategy has not been defined. Generally, this type of lymphoma is treated with surgery, intrathecal chemotherapy, and postoperative chemoradiation therapy. The prognosis is poor. Herein, we present a case of primary brain NK/T cell lymphoma in a 50-year-old immunocompetent Chinese female and review the literature. The patient underwent intracranial tumor resection and was subsequently treated with a PD1 monoclonal antibody (Sintilimab) combined with chemotherapy. The patient survived 15 months after diagnosis. This is the first report of PCNS ENK/TCL treated with surgery and chemotherapy combined with immunotherapy and suggests an effective treatment regimen for PCNS ENK/TCL.

Survival Analysis of Hepatosplenic T Cell Lymphoma: A Population-Based Study Using SEER.

PURPOSE: Hepatosplenic T cell lymphoma (HSTCL) is a rare tumor that lacks data to guide management decisions. To shed light on the nature and therapy of the entity, we conducted this study. PATIENTS AND METHODS: We retrospectively reviewed patients diagnosed with HSTCL between 1975 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database to analyze the clinical characteristics and survival outcome compared with PTCL-NOS and ALK+ ALCL. RESULTS: A total of 123 HSTCLs were included in the analysis. Most patients were aged ≤60 years (81.3%) and had a male predominance (69.1%). Organs with lymphoma infiltration of HSTCL were more common in the spleen (98.4%). The 1-year, 3-year, and 5-year overall survival (OS) rates in the entire HSTCL cohort were 56.9% (95% CI, 47.5-66.3%), 37.6% (95% CI, 28.0-47.2%), and 31.6.0% (95% CI, 22.2-41.0%), respectively. The overall survival (OS) of HSTCL patients was similar to that of PTCL-NOS patients (P = 0.128) but worse than that of patients with ALK+ ALCL (P < 0.001). The disease-specific survival (DSS) of HSTCL patients was worse than that of PTCL-NOS and ALK+ ALCL patients (P < 0.05). The same tendency was found in the matched data set. Cox regression analyses indicated that the use of chemotherapy combined with topical treatment may improve the survival of patients with HSTCL. CONCLUSION: A higher proportion of young patients and a strong male predominance were found in HSTCL. Chemotherapy combined with topical treatment may be an optional regimen. Further studies are needed to intensify efforts in dealing with this rare but unfavorable disease.

Ferroptosis-Related Gene Signature: A New Method for Personalized Risk Assessment in Patients with Diffuse Large B-Cell Lymphoma.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease, which makes prognostic prediction challenging. The rapid development of research on ferroptosis provides the possibility of its use in prognosis in cancer patients. The aim of the current investigation was to perform a systematic study of ferroptosis and DLBCL prognosis to identify prognostic biomarkers in DLBCL. MATERIALS AND METHODS: A total of 884 DLBCL patients from the Gene Expression Omnibus database were included in this study and were divided into a training set and a validation set. Univariate Cox regression analysis was used to investigate relationships between gene expression and prognostic values. Ferroptosis-related genes associated with overall survival in the training set were then extracted, and the least absolute shrinkage and selection operator Cox regression model was used to establish an eight-gene signature, comprising ZEB1, PSAT1, NGB, NFE2L2, LAMP2, HIF1A, FH, and CXCL2. RESULTS: The signature exhibited significant independent prognostic value in both the training set and the validation set. It also exhibited strong prognostic value in subgroup analysis. A nomogram integrating the eight-gene signature and components of the International Prognostic Index facilitated reliable prognostic prediction. CONCLUSION: A novel and reliable ferroptosis-related gene signature that can effectively classify DLBCL patients into high-risk and low-risk groups in terms of survival rate was developed. It could be used for prognostic prediction in DLBCL patients. Targeting ferroptosis may be a therapeutic alternative in DLBCL.

Correlation between the structure and skin permeability of compounds.

A three-descriptor quantitative structure-activity/toxicity relationship (QSAR/QSTR) model was developed for the skin permeability of a sufficiently large data set consisting of 274 compounds, by applying support vector machine (SVM) together with genetic algorithm. The optimal SVM model possesses the coefficient of determination R2 of 0.946 and root mean square (rms) error of 0.253 for the training set of 139 compounds; and a R2 of 0.872 and rms of 0.302 for the test set of 135 compounds. Compared with other models reported in the literature, our SVM model shows better statistical performance in a model that deals with more samples in the test set. Therefore, applying a SVM algorithm to develop a nonlinear QSAR model for skin permeability was achieved.

Primary Mediastinal B-Cell Lymphoma: Novel Precision Therapies and Future Directions.

Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinicopathologic disease from other types of diffuse large B-cell lymphoma (DLBCL) with unique prognostic features and limited availability of clinical data. The current standard treatment for newly diagnosed PMBCL has long been dependent on a dose-intensive, dose-adjusted multi-agent chemotherapy regimen of rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH). Recent randomized trials have provided evidence that R-CHOP followed by consolidation radiotherapy (RT) is a valuable alternative option to first-line treatment. For recurrent/refractory PMBCL (rrPMBCL), new drugs such as pembrolizumab and CAR-T cell therapy have proven to be effective in a few studies. Positron emission tomography-computed tomography (PET-CT) is the preferred imaging modality of choice for the initial phase of lymphoma treatment and to assess response to treatment. In the future, baseline quantitative PET-CT can be used to predict prognosis in PMBCL. This review focuses on the pathology of PMBCL, underlying molecular basis, treatment options, radiotherapy, targeted therapies, and the potential role of PET-CT to guide treatment choices in this disease.

Identification and Validation of a Prognostic Gene Signature for Diffuse Large B-Cell Lymphoma Based on Tumor Microenvironment-Related Genes.

Diffuse large B-cell lymphoma (DLBCL) is an extremely heterogeneous tumor entity, which makes prognostic prediction challenging. The tumor microenvironment (TME) has a crucial role in fostering and restraining tumor development. Consequently, we performed a systematic investigation of the TME and genetic factors associated with DLBCL to identify prognostic biomarkers for DLBCL. Data for a total of 1,084 DLBCL patients from the Gene Expression Omnibus database were included in this study, and patients were divided into a training group, an internal validation group, and two external validation groups. We calculated the abundance of immune-stromal components of DLBCL and found that they were related to tumor prognosis and progression. Then, differentially expressed genes were obtained based on immune and stromal scores, and prognostic TME-related genes were further identified using a protein-protein interaction network and univariate Cox regression analysis. These genes were analyzed by the least absolute shrinkage and selection operator Cox regression model to establish a seven-gene signature, comprising TIMP2, QKI, LCP2, LAMP2, ITGAM, CSF3R, and AAK1. The signature was shown to have critical prognostic value in the training and validation sets and was also confirmed to be an independent prognostic factor. Subgroup analysis also indicated the robust prognostic ability of the signature. A nomogram integrating the seven-gene signature and components of the International Prognostic Index was shown to have value for prognostic prediction. Gene set enrichment analysis between risk groups demonstrated that immune-related pathways were enriched in the low-risk group. In conclusion, a novel and reliable TME relevant gene signature was proposed and shown to be capable of predicting the survival of DLBCL patients at high risk of poor survival.

Optimal Courses of Chemotherapy Combined with Radiotherapy for Low-Risk Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Propensity Score Matching Analysis.

PURPOSE: This retrospective study compared effectiveness between ≤4 cycles and ≥5 cycles of L-asparaginase/pegaspargase-based chemoradiation in newly diagnosed low-risk extranodal natural killer/T-cell lymphoma (ENKTL), nasal type classified according to the Prognostic Index of Natural Killer (PINK) lymphoma model. PATIENTS AND METHODS: Patients were categorized into ≤4-cycle (2-4 chemotherapy cycles, n = 166) and ≥5-cycle groups (5-6 cycles, n = 86). Propensity score matching analysis was used to reduce potential confounding bias between the two groups. Treatment responses, adverse events, and survival outcomes between the two groups were analyzed. RESULTS: No matter before or after matching (65 in the ≤4-cycle group, 65 in the ≥5-cycle group), response rates and survival outcomes were similar between the ≤4-cycle and ≥5-cycle groups. Incidences of grade 1-2 anemia and transaminase elevation were higher in the ≥5-cycle group. After matching, for stage IE disease, there were no differences in response rates and survival outcomes between the two groups. For stage IIE disease, the complete response rate was higher in the ≥5-cycle group (72.4% vs 92.6%, p = 0.049), and the 3-year overall survival (65.5% vs 85.2%, p = 0.024) and 3-year progression-free survival (58.6% vs 81.5%, p = 0.027) rates were significantly extended in the ≥5-cycle group. CONCLUSION: When chemoradiotherapy strategies with L-asparaginase/pegaspargase-based regimens are applied to modern low-risk ENKTL patients classified according to the PINK model, it may be better to moderately extend chemotherapy courses in patients with stage IIE disease.

Potential of circular RNA itchy E3 ubiquitin protein ligase as a biomarker and treatment target for multiple myeloma.

BACKGROUND: This study aimed to investigate the association of circular RNA itchy E3 ubiquitin protein ligase (circ-ITCH) expression with disease risk, clinical characteristics, progression-free survival (PFS) and overall survival (OS) of multiple myeloma (MM), and to explore the influence of circ-ITCH overexpression on MM cell activities in vitro. METHODS: Bone marrow samples from 92 MM patients and 30 healthy controls were collected, and circ-ITCH expression was detected by quantitative polymerase chain reaction. PFS and OS in MM patients were calculated. Circ-ITCH in human MM cell lines and normal bone marrow mononuclear cells (BMMCs) were detected. Circ-ITCH overexpression and control overexpression plasmids were transfected to U226 cell line, and cell proliferation as well as apoptosis were assessed. RESULTS: Circ-ITCH expression was under-expressed in MM patients compared to healthy controls. And receiver operating characteristic curve displayed that circ-ITCH could distinguish MM patients from healthy controls [area under curve: 0.809 (95% CI: 0.722-0.895)]. Additionally, circ-ITCH high expression was associated with decreased International Staging System (ISS) stage in MM patients. Kaplan-Meier curves and Cox's regression analysis displayed that circ-ITCH expression was positively correlated with PFS and OS. In vitro, circ-ITCH expression was lower in MM cell lines (including RPMI8226, U226 and NCI-H929) compared to normal BMMCs. In U226 cells, cell proliferation was decreased but apoptosis was elevated by circ-ITCH overexpression. CONCLUSIONS: Circ-ITCH might serve as a potential biomarker and treatment target for MM.

Analysis of Genomic Alteration in Primary Central Nervous System Lymphoma and the Expression of Some Related Genes.

Primary central nervous system lymphoma (PCNSL) is a rare and special type of non-Hodgkin lymphoma. The treatment of PCNSL is comprehensive, combining surgery, radiotherapy, and chemotherapy. However, the outcome is poor because of its high invasiveness and rate of recurrence. We analyzed 22 cases of PCNSL using next-generation sequencing (NGS) to detect 64 candidate genes. We used immunohistochemical methods to analyze gene expression in 57 PCNSL samples. NGS showed that recurrent mutations in KMT2D and CD79B, components of the NF-κB pathway, accounted for 65% of total mutations in PCNSL samples. The most frequent mutated gene was PIM1 (77.27%, 17/22), followed by MYD88 (63.64%, 14/22), CD79B (69.09%, 13/22), and KMT2D (50.00%, 11/22). Mutations of the CD79B gene were associated with an inferior progression-free survival (PFS), and GNA13 gene mutations were associated with a shorter PFS and overall survival (OS) in PCNSL patients (P < .05). PIM1 and MYD88 were highly expressed in PCNSL patients and were related to their OS time. MYD88 overexpression might be an independent and poor prognostic predictor of OS time. In summary, we identified highly recurrent genetic lesions in CD79B and KMT2D, components of the NF-κB pathway, in PCNSL and validated the expression of PIM1 and MYD88 related to poor survival, thereby providing novel insights into the pathogenesis and precision medicine of PCNSL.

Lysophosphatidic Acid is a Biomarker for Peritoneal Carcinomatosis of Gastric Cancer and Correlates with Poor Prognosis.

BACKGROUND: Peritoneal carcinomatosis (PC) is an important cause of morbidity and mortality among patients with gastric cancer. Thus, it is important to identify an ideal biomarker for PC. METHODS: Plasma and ascites samples were collected from gastric cancer patients with PC and a control group. Lysophosphatidic acid (LPA) levels were tested and analyzed. RESULTS: The plasma LPA levels of gastric cancer patients with PC were significantly higher than those in gastric cancer patients after radical resection (p = 0.046) and healthy volunteers (p < 0.001). Besides, plasma LPA levels were statistically lower after chemotherapy in gastric cancer patients with PC (p = 0.028). Furthermore, the ascites LPA levels were significantly higher in gastric cancer patients with peritoneal carcinomatosis than those in liver cirrhosis patients (p < 0.001). Moreover, ascites LPA levels were statistically lower after intraperitoneal chemotherapy injection than before (p < 0.001). In addition, the plasma LPA levels were significantly associated with serum CA125 levels (p = 0.032) and TNM stage in gastric cancer patients (p = 0.009). Individuals with plasma LPA levels >20,000 ng/mL had significantly worse overall survival (OS) than those with plasma LPA levels <20,000 ng/mL group (p = 0.006). In addition the group with ascites LPA levels >24,000 ng/mL showed significantly worse progression-free survival (PFS) and OS (p < 0.001 in PFS and OS). CONCLUSIONS: This study demonstrated that LPA levels in plasma and ascites may be useful diagnostic biomarkers for PC of gastric cancer and that higher levels are associated with poor prognosis.

STAT3 mediates multidrug resistance of Burkitt lymphoma cells by promoting antioxidant feedback.

Burkitt lymphoma (BL) is a highly aggressive B-cell neoplasm. Although BL is relatively sensitive to chemotherapy, some patients do not respond to initial therapy or relapse after standard therapy, which leads to poor prognosis. The mechanisms underlying BL chemoresistance remain poorly defined. Here, we report a mechanism for the relationship between the phosphorylation of STAT3 on Tyr705 and BL chemoresistance. In chemoresistant BL cells, STAT3 was activated and phosphorylated on Tyr705 in response to the generation of the reactive oxygen species (ROS), which induced Src Tyr416 phosphorylation after multi-chemotherapeutics treatment. As a transcription factor, the elevated phosphorylation level of STAT3Y705 increased the expression of GPx1 and SOD2, both of which protected cells against oxidative damage. Our findings revealed that the ROS-Src-STAT3-antioxidation pathway mediated negative feedback inhibition of apoptosis induced by chemotherapy. Thus, the phosphorylation of STAT3 on Tyr705 might be a target for the chemo-sensitization of BL.

Multiple Roles of WNT5A in Breast Cancer.

Breast cancer is one of the most common malignant tumors of women. Modern combinatorial therapeutic regimens can reduce patient tumor burdens to undetectable levels, yet in many cases these tumors will relapse. Understanding of breast cancer biology, developing more potent therapeutic approaches, and overcoming resistance are of great importance. WNT5A is a non-canonical signaling member of the WNT family. Its role in breast cancer still remains unclear. Most of the evidence shows that WNT5A is a suppressor in breast cancer and loss of its expression is associated with poor prognosis, while some evidence suggests the tumorigenicity of WNT5A. WNT signaling molecules are potent targets for treatment of cancer. Therefore, understanding the role of WNT5A in breast cancer may provide new ideas and methods for breast cancer treatment. We review the evidence concerning WNT5A and breast cancer involving the signaling pathways and the molecular-targeted therapy of WNT5A. Our results show that the role WNT5A plays depends on the availability of key receptors and intercellular interactions among different cell types.

WITHDRAWN: ALDH1A1 induces resistance to CHOP in diffuse large B-cell lymphoma through activation of the JAK2/STAT3 pathway.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

ALDH1A1 induces resistance to CHOP in diffuse large B-cell lymphoma through activation of the JAK2/STAT3 pathway.

Increasing evidence has shown that aldehyde dehydrogenase 1A1 (ALDH1A1), a detoxifying enzyme, is responsible for chemoresistance in a variety of tumors. Although the majority of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), chemoresistance is a common cause of treatment failure. This study aims to investigate the significance of ALDH1A1 expression and the mechanism by which ALDH1A1 is involved in the chemoresistance of DLBCL cells. ALDH1A1 expression was assessed in 88 DLBCL tissues by immunohistochemistry. The association between ALDH1A1 expression and outcome was evaluated. We also investigated the effect of ALDH1A1 on CHOP resistance in DLBCL cells using functional analysis. ALDH1A1 expression levels were upregulated in patients with stable or progressive disease after CHOP and its expression positively correlated with expression of STAT3 and p-STAT3. In keeping with these observations, ALDH1A1 expression was significantly associated with short survival of DLBCL patients who received CHOP chemotherapy. In functional assays in Pfeiffer cells, overexpression of ALDH1A1 conferred resistance to CHOP, while silencing of ALDH1A1 using short hairpin RNA had the opposite effect. Furthermore, we also observed that ALDH1A1 could regulate the JAK2/STAT3 pathway, while inhibition of the JAK2/STAT3 pathway by WP1066 negated the effect of ALDH1A1 overexpression. These observations reveal that ALDH1A1 induces resistance to CHOP through activation of the JAK2/STAT3 pathway in DLBCL, and its targeting provides a potential strategic approach for reversing CHOP resistance.