Prognostic value of prognostic nutritional index on extranodal natural killer/T-cell lymphoma patients: A multicenter propensity score matched analysis of 1022 cases in Huaihai Lymphoma Working Group.

Prognostic nutritional index (PNI), comprised of serum albumin level and lymphocyte count, is associated with the prognosis of several malignant diseases, while the prognostic value of PNI in extranodal natural killer/T cell lymphoma, nasal type (ENKTL) remains unclear. This retrospective multicenter study aimed to investigate the value of PNI in predicting the prognosis of newly diagnosed ENKTL patients by using propensity score matched analysis (PSM). A total of 1022 newly diagnosed ENKTL patients were retrieved from Huaihai Lymphoma Working Group and clinicopathological variables were collected. MaxStat analysis was used to calculate the optimal cut-off points of PNI and other continuous variables. The median age at diagnosis was 47 years and 69.4% were males, with the 5-year OS of 71.7%. According to the MaxStat analysis, 41 was the optimal cut-off point for PNI. The Pseudo R2 before matching was 0.250, and it decreased to less than 0.019 after matching. Confounding factors of the two groups were well balanced after PSM. Multivariable analysis revealed that PNI, Korean Prognostic Index (KPI), eastern cooperative oncology group performance status (ECOG PS), the prognostic index of natural killer lymphoma (PINK) and hemoglobin were independent prognostic factors for ENKTL. The results of subgroup analysis demonstrated that patients with low PNI could predict worse prognosis and re-stratify patients in ECOG PS ≥ 2, EBER-positive, the International Prognostic Index (IPI) (HIR + HR), and PINK (HR) groups. PNI combined with IPI, PINK and KPI could improve the prediction efficiency. In conclusion, PNI could accurately stratify the prognosis of ENKTL by PSM analysis and patients with low PNI had poorer prognosis.

AKAP12 and IGFBP4 Are Prognostic Factors for Chronic Lymphocytic Leukemia.

INTRODUCTION: The aim of this study was to develop a prognostic model for chronic lymphocytic leukemia (CLL). METHODS: GEO2R was used to retrieve the gene expression data of CLL and normal B cells from the Gene Expression Omnibus (GEO; GSE22529 and GSE50006 datasets) database. Practical Extraction and Report Language was used to extract the gene expression and overall survival (OS) data of CLL patients from the Chronic Lymphocytic Leukemia - ES (CLLE-ES) project in the International Cancer Genome Consortium (ICGC) database. Cox regression with Lasso was used to create and validate a prognostic model for CLL. RESULTS: A total of 267 genes exhibited differential expression between CLL and normal B cells. Cox univariate analysis identified 14 DEGs that correlated with OS. Lasso multivariate evaluation demonstrated that AKAP12 and IGFBP4 are independent prognostic factors for CLL. Kaplan-Meier survival analysis revealed a significant association between the estimated risk score and survival. The area under the receiver operating characteristic curve was calculated to be 0.97, indicating high predictive accuracy. In addition, high AKAP12 and IGFBP4 risk scores were associated with the high incidence of trisomy 12q. CONCLUSION: Taken together, AKAP12 and IGFBP4 are independent prognostic factors for CLL.

The efficacy and safety of low-dose rituximab in immune thrombocytopenia: a systematic review and meta-analysis.

Rituximab has been frequently used as a second-line treatment for patients with immune thrombocytopenia (ITP). Recently, several studies have proposed low-dose (100 mg or 100mg/m2 per week for 4 weeks) rituximab instead of the standard dose of 375mg/m2 per week for 4 weeks to treat ITP patients. The aim of this review was to systematically evaluate the efficacy and safety of low-dose rituximab for patients with ITP. Pubmed, Web of Science, Cochrane Library and Embase were searched to identify the clinical studies published in full text or abstract that met the predefined inclusion criteria. Efficacy analysis was restricted to the studies enrolling five or more patients. While safety analysis was evaluated based on all the studies reported adverse events. Nine studies (329 patients) were included for effect assessment of low-dose rituximab treatment on the patients with ITP. The pooled overall response rate was 63% (95% CI, 0.54-0.71) while the pooled complete response was 44% (95% CI, 0.33-0.55). Thirty-one patients were reported to experience adverse effects associated with rituximab, among them 30 cases suffered mild to moderate side-effects (grade1-2). Only one patient developed into interstitial pneumonia (grade3). No death was reported. Low-dose rituximab exhibited a satisfactory efficacy and safety profile, indicating that this regimen is a promising therapy for ITP, and should be further investigated through randomized clinical trials with standard-dose rituximab.

Two-Step Centrifugation Method for Subpicomolar Surface-Enhanced Raman Scattering Detection.

The potentiality of surface-enhanced Raman scattering (SERS) to detect ultralow concentrations of analyte has attracted much attention in detection of trace components in both medicinal and environmental samples. However, detection at trace concentration usually requires sophisticated systems. Here, we present an ultrasensitive and facile SERS approach, a two-step centrifugation method, which achieved a detection limit of 500 fM with phenformin hydrochloride and risperidone as acidic and alkaline analyte, respectively. This method consists of two steps: (1) centrifuging colloidal silver to increase nanoparticles' concentration and to remove small-size nanoparticles, thus increasing the chance of analyte adsorption on large nanoparticles that have strong SERS activity; (2) centrifuging samples after the analytes were mixed with nanoparticles. After the first centrifugation and mixing with aqueous analyte, the colloidal silver is either flocculated (for high-concentration samples) or forms a nanoparticle-analyte complex (for low-concentration samples). Until the second centrifugation, the concentration of analyte and hot-spot formation is significantly increased, and thus a high SERS enhancement factor is obtained. In short, the two-step centrifugation method overcomes drawbacks of the traditional method, which demands not only sophisticated operation but also expensive instruments, to fully exploit the potential of SERS detection.

Long-term effect of high-dose dexamethasone with or without low-dose dexamethasone maintenance in untreated immune thrombocytopenia.

BACKGROUND: To tackle the problems associated with high-dose dexamethasone (HD-DXM) in patients with immune thrombocytopenia (ITP). AIM: To compare the efficacy of HD-DXM with or without low-dose dexamethasone maintenance in untreated ITP patients. RESULTS: Dexamethasone (40 mg/day) was given in 4-day pulses every 14 days for 3 cycles in 61 patients with ITP. Among them, 30 cases were given dexamethasone (0.035 mg/kg per day) for maintenance between pulsed HD-DXM and after 3 HD-DXM courses (HD-DXM-M group) and another 31 cases did not receive dexamethasone maintenance (HD-DXM-nM group). The control group comprised the patients who received prednisone (prednisone group). The following results were obtained: (1) at the end of the 3rd cycle, the overall response rate (ORR) was higher in the HD-DXM group than in the prednisone group; (2) the ORR of the HD-DXM group peaked after the 3rd cycle; (3) the ORR after each course was higher in the HD-DXM-M group than in the HD-DXM-nM group; (4) in the 12th month after HD-DXM discontinuation, the relapse rate of the HD-DXM-M group was lower than that of the other groups (prednisone and HD-DXM-nM). CONCLUSION: Treatment with 3 cycles of HD-DXM pulses with low-dose dexamethasone maintenance is an effective method for untreated ITP.

Homoharringtonine combined with cytarabine to treat chronic myelogenous leukemia in myeloid blast crisis and its impact on bone marrow CD34+CD7+ cells.

BACKGROUND: The therapeutic response of chronic myelogenous leukemia in myeloid blast crisis (CML-MBC) is very poor. AIM: To explore the therapeutic effect of homoharringtonine (HHT) combined with cytarabine (HA regimen) on CML-MBC and its influence on bone marrow CD34+CD7+ cells. RESULTS: Thirty-four patients with CML-MBC were treated with the HA regimen and bone marrow CD34+CD7+ cells were assayed prior to and after treatment. Among 33 evaluable patients, the overall hematological response (complete/ partial hematological response and hematological improvement) was 60.1%. Seven patients (21.2%) had a cytogenetic response 12 months after treatment. In the untreated CMLMBC patients, the proportion of bone marrow CD34+CD7+ cells was much higher than in the control group (19.4 ± 7.9 vs. 4.4 ± 1.5%, p < 0.05) and decreased to 14.1 ± 7.1% (p < 0.05) after treatment. Before treatment, the proportion of CD34+CD7+ cells was lower in the patients who had a hematological response to the HA regimen than in the patients who did not respond. CONCLUSION: The HA regimen is an effective treatment for CML-MBC and CD34+CD7+ cells may be one of the valuable clinical parameters to assess treatment effectiveness.

Clinical and molecular characteristics of acute myeloid leukemia and the dismal prognosis of TP53 mutations in a real-world setting.

OBJECTIVES: This study aimed to evaluate the incidence and prognostic significance of common cytogenetic and molecular abnormalities in patients with TP53-mutated and non-TP53-mutated acute myeloid leukemia (AML). METHODS: We retrospectively analyzed the clinical data of 326 patients with newly diagnosed AML hospitalized in our institution between October 2015 and June 2021. Classification variables were reported as percentages and compared by χ2 tests. Survival rates were evaluated by the Kaplan-Meier method. RESULTS: The incidence of TP53 mutations in AML patients in this clinic was 9.8%, of whom 87.5% patients were over 50 years old. The common concurrent mutations of TP53 were DNMT3A, IDH2, NRAS and TET2. Patients with a TP53 variant allele frequency (VAF) ≤ 40% had better overall survival (OS) than patients with a VAF >40%. Compared with non-TP53-mutated patients, significantly more TP53-mutated patients were gene-fusion negative, +mar, - 7/del (7q), - 5/del (5q), - 17/17p-, - 12/12p-, incomplete (inc) karyotype, or complex karyotype (CK), and had FLT3-ITD or IDH2 mutations, as well as a lower complete remission (CR) rate (31.3%) and higher recurrence rate (80.0%). The 2-year OS rates of TP53-mutated and non-TP53-mutated patients were 18.8% and 47.3%, respectively (P < 0.001). Univariate analysis showed that non-TP53-mutated patients with MLL family gene fusion, +mar or - 17/17p - karyotype, and FLT3-ITD mutations had a poor prognosis, while t(8; 21) karyotype was associated with a better prognosis. TP53-mutated patients with - 7/del (7q) or - 5/del (5q) karyotype had a poor prognosis. CONCLUSIONS: The cytogenetic and molecular landscapes differed between TP53-mutated and non-TP53-mutated patients, and some abnormalities had different values between them.

Comparative analysis of clinicopathologic characteristics and prognosis between nasal and nonnasal extranodal NK/T-cell lymphoma.

BACKGROUND: The clinicopathologic characteristics and prognosis of nasal and nonnasal extranodal natural killer T-cell lymphoma (ENKTL) are considered to be different. However, the underlying features responsible for these differences are not well clarified especially in the era of asparaginase therapy. METHODS: In total, 1007 newly diagnosed ENKTL patients from 11 medical centers were included in this study. Clinicopathologic characteristics and survival data were collected. The chi-squared test and Kruskal-Wallis test were utilized for the comparison of different groups. Univariable and multivariable Cox proportional hazards models were used to screen prognostic factors. RESULTS: Overall, 869 (86.3%) patients were nasal forms. Compared to patients with nasal ENKTL, nonnasal patients were at more advanced stages and had poor performance status, bone marrow involvement, elevated serum lactate dehydrogenase (LDH), and CD56-negative status (p < 0.05). The 5-year overall survival (OS) for nasal and nonnasal patients were 65.6% and 45.0%, respectively. The OS of nasal forms patients were superior to nonnasal patients, especially in Eastern Cooperative Oncology Group performance status (ECOG PS) (≥2), advanced stage, KPI (HIR/HR), IPI (HIR/HR), PINK (HR), and high EBV DNA load groups. In patients treated with pegaspargase/L-asparaginase-based regimens, the OS of nasal patients was better than that of nonnasal patients. After adjusting the covariates of age, stage, ECOG PS score, LDH, B symptoms, and BM involvement, results showed that the nonnasal site was associated with poor survival of ENKTL. CONCLUSIONS: The clinicopathologic characteristics and prognosis of nasal and nonnasal ENKTL patients are different. Nasal forms patients had superior OS than nonnasal patients, especially in the era of asparaginase.

Nucleophosmin 1: from its pathogenic role to a tantalizing therapeutic target in acute myeloid leukemia.

Nucleophosmin 1 (NPM1, also known as B23) is a multifunctional protein involved in a variety of cellular processes, including ribosomal maturation, centrosome replication, maintenance of genomic stability, cell cycle control, and apoptosis. NPM1 is the most commonly mutated gene in adult acute myeloid leukemia (AML) and is present in approximately 40% of all AML cases. The underlying mechanisms of mutant NPM1 (NPM1mut) in leukemogenesis remain unclear. This review summarizes the structure and physiological function of NPM1, mechanisms underlying the pathogenesis of NPM1-mutated AML, and the potential role of NPM1 as a therapeutic target. It is reported that dysfunctional NPM1 might cause AML pathogenesis via its role as a protein chaperone, inhibiting differentiation of leukemia stem cells and regulation of non-coding RNAs. Besides conventional chemotherapies, NPM1 is a promising therapeutic target against AML that warrants further investigation. NPM1-based therapeutic strategies include inducing nucleolar relocalisation of NPM1 mutants, interfering with NPM1 oligomerization, and NPM1 as an immune response target.

[Effect of Hypoxia Inducible Factor-1α on Chemosensitivity of B-ALL Cells to Vincristine and Its Mechanism].

OBJECTIVE: To explore the effect of hypoxia on the chemosensitivity of B-acute lymphoblastic leukemia （B-ALL） cells to Vincristine (VCR) and the mechanisms. METHODS: B-ALL cells SUP-B15, Nalm-6 and RS4;11 were selected as the research objects. The cells were divided into the control group and the hypoxia mimic group (CoCl2 pretreatment). The two groups were treated with VCR at different concentrations for 24 hours, CCK-8 was used to detect cell viability, flow cytometry was used to detect cell apoptosis, and Western bolt method was used to detect hypoxia inducible factor (HIF-1α), BAX, Bcl-2 and ß-actin protein expression. Quantitative real-time fluorescent PCR (qRT-PCR) was used to detect BAX and ß-actin mRNA levels. RESULTS: CoCl2 could simulate hypoxic environment to induce the expression of HIF-1α. The cells SUP-B15 and RS4;11 of the hypoxia mimic group were lower sensitivity to VCR as compared with the control group; the apoptosis rate of the hypoxia mimic group was lower than that of the control group after 80 nmol/L VCR treatment. The expression levels of BAX protein and mRNA in the hypoxia mimic group were lower than those of the control group, and there was no significant difference in the expression levels of Bcl-2 protein between two groups. CONCLUSION: Under hypoxic conditions, HIF-1α may mediate VCR resistance in B-ALL cells by downregulating the pro-apoptotic protein BAX.

[Effect of Hypoxia Inducible Factor-1α on Chemosensitivity of B-ALL Cells to Vincristine and Its Mechanism].

OBJECTIVE: To explore the effect of hypoxia on the chemosensitivity of B-acute lymphoblastic leukemia （B-ALL） cells to Vincristine (VCR) and the mechanisms. METHODS: B-ALL cells SUP-B15, Nalm-6 and RS4;11 were selected as the research objects. The cells were divided into the control group and the hypoxia mimic group (CoCl2 pretreatment). The two groups were treated with VCR at different concentrations for 24 hours, CCK-8 was used to detect cell viability, flow cytometry was used to detect cell apoptosis, and Western bolt method was used to detect hypoxia inducible factor (HIF-1α), BAX, Bcl-2 and ß-actin protein expression. Quantitative real-time fluorescent PCR (qRT-PCR) was used to detect BAX and ß-actin mRNA levels. RESULTS: CoCl2 could simulate hypoxic environment to induce the expression of HIF-1α. The cells SUP-B15 and RS4;11 of the hypoxia mimic group were lower sensitivity to VCR as compared with the control group; the apoptosis rate of the hypoxia mimic group was lower than that of the control group after 80 nmol/L VCR treatment. The expression levels of BAX protein and mRNA in the hypoxia mimic group were lower than those of the control group, and there was no significant difference in the expression levels of Bcl-2 protein between two groups. CONCLUSION: Under hypoxic conditions, HIF-1α may mediate VCR resistance in B-ALL cells by downregulating the pro-apoptotic protein BAX.

Epidemiologic Characteristics, Prognostic Factors, and Treatment Outcomes in Primary Central Nervous System Lymphoma: A SEER-Based Study.

OBJECTIVE: This study was conducted in order to study the clinical characteristics, prognostic factors, and treatment outcomes in patients with primary central nervous system lymphoma (PCNSL). MATERIALS AND METHODS: The data of a total of 5,166 PCNSL patients diagnosed between 2000 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database were obtained. RESULTS: The mean age was 63.1 ± 14.9 years, with a male to female ratio of 1.1:1.0. The most common histologic subtype was diffuse large B-cell lymphoma (DLBCL) (84.6%). The 1-, 3-, and 5-year overall survival (OS) rates were 50.1%, 36.0%, and 27.2%, respectively, and the corresponding disease-specific survival (DSS) rates were 54.4%, 41.3%, and 33.5%, respectively. Multivariate analysis with Cox regression showed that race, sex, age, marital status, surgical resection, and chemotherapy were independent prognostic factors for OS and DSS, but radiotherapy was only for OS. Nomograms specially for DLBCL were established to predict the possibility of OS and DSS. The concordance index (C-index) values of OS and DSS were 0.704 (95% CI 0.687-0.721) and 0.698 (95% CI 0.679-0.717), suggesting the high discrimination ability of the nomograms. CONCLUSION: Surgical resection and/or chemotherapy was favorably associated with better OS and DSS. However, radiotherapy was not beneficial for OS and DSS in the long term. A new predictive nomogram and a web-based survival rate calculator we developed showed favorable applicability and accuracy to predict the long-term OS for DLBCL patients specifically.

[Effect of CXCR4 on the Treatment Response and Prognosis of Carfilzomib in Multiple Myeloma].

OBJECTIVE: To explore the effect of CXCR4 on the treatment response and prognosis of Carfilzomib (CFZ) in multiple myeloma. METHODS: Dataset GSE69078 based on microarray data from two CFZ-resistant MM cell lines and their corresponding parental cell lines (KMS11-KMS11/CFZ and KMS34-KMS34/CFZ) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Protein-protein interaction (PPI) network was established to identify the key genes involved in CFZ resistance acquisition. Finally, the prognostic roles of the CFZ risistance key genes in MM using MMRF-CoMMpass data study was verified. RESULTS: 44 up-regulated and 46 down-regulated DEGs were identified. Top 10 hub genes (CCND1, CXCR4, HGF, PECAM1, ID1, HEY1, TCF4, HIST1H4J, HIST1H2BD and HIST1H2BH) were identified via Protein-protein interaction (PPI) network analysis. The CoMMpass data showed that high CXCR4 expression showed correlation to relative higher relapse and progress rates and the overall survival was significant decreased in high CXCR4 patients (P=0.013). CONCLUSION: CXCR4 perhaps plays a crucial role in CFZ acquired resistance, which might help identifying potential CFZ-sensitive patients before treatment and providing a new therapeutic target in CFZ-resistant MM.

Prognostic value of the controlling nutritional status score in patients with myelodysplastic syndromes.

Background: Myelodysplastic syndromes (MDS) are a heterogeneous spectrum of clonal hematopoietic disorders with varying degrees of cytopenia and morphologic dysplasia. The controlling nutritional status (CONUT) score, an easy-to-use tool for assessing the nutritional status, was reported as an independent prognostic factor in cancer patients. However, its role in patients with MDS is unclear. Objective: We aimed to explore the impact of CONUT score on the prognosis of patients with MDS, which is of great significance for clinical treatment. Methods: A total of 121 patients with MDS were analyzed. The CONUT score was calculated prior to therapy. The bio-informatics tool X-tile was used to define the CONUT score and the threshold of 4 points was determined to predict the prognosis. Patients were divided into CONUTlow and CONUThigh groups, and the characteristics were compared between two groups. Results: Results show that CONUTlow was associated with better overall survival (OS) than CONUThigh patients (Median OS, 30.20 vs. 19.63 months, p = 0.0003). However, there were no statistical differences in progression-free survival (PFS) between the two groups (p = 0.2683). Results of univariate and multivariate COX proportional hazard analysis adjusted for bone marrow blasts level, platelet count, International Prognostic Scoring System (IPSS) scores, gender, and hemoglobin (Hb) level showed that the CONUT score was useful in the evaluation standard of OS of MDS (hazard ratio (HR) 2.297, 95% CI 1.441-3.663, p < 0.001). Conclusions: The CONUT, as a novel immuno-nutritional biomarker, may be useful in predicting the OS of MDS.

LASSO Model Better Predicted the Prognosis of DLBCL than Random Forest Model: A Retrospective Multicenter Analysis of HHLWG.

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous non-Hodgkin's lymphoma with great clinical challenge. Machine learning (ML) has attracted substantial attention in diagnosis, prognosis, and treatment of diseases. This study is aimed at exploring the prognostic factors of DLBCL by ML. Methods: In total, 1211 DLBCL patients were retrieved from Huaihai Lymphoma Working Group (HHLWG). The least absolute shrinkage and selection operator (LASSO) and random forest algorithm were used to identify prognostic factors for the overall survival (OS) rate of DLBCL among twenty-five variables. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were utilized to compare the predictive performance and clinical effectiveness of the two models, respectively. Results: The median follow-up time was 43.4 months, and the 5-year OS was 58.5%. The LASSO model achieved an Area under the curve (AUC) of 75.8% for the prognosis of DLBCL, which was higher than that of the random forest model (AUC: 71.6%). DCA analysis also revealed that the LASSO model could augment net benefits and exhibited a wider range of threshold probabilities by risk stratification than the random forest model. In addition, multivariable analysis demonstrated that age, white blood cell count, hemoglobin, central nervous system involvement, gender, and Ann Arbor stage were independent prognostic factors for DLBCL. The LASSO model showed better discrimination of outcomes compared with the IPI and NCCN-IPI models and identified three groups of patients: low risk, high-intermediate risk, and high risk. Conclusions: The prognostic model of DLBCL based on the LASSO regression was more accurate than the random forest, IPI, and NCCN-IPI models.

A Novel Prognostic Index Model for Adult Hemophagocytic Lymphohistiocytosis: A Multicenter Retrospective Analysis in China.

Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder with rapid progression and poor survival. Individual treatment strategy is restricted, due to the absence of precise stratification criteria. In this multicenter retrospective study, we aimed to develop a feasible prognostic model for adult HLH in China. A total of 270 newly diagnosed patients of adult HLH were retrieved from the Huaihai Lymphoma Working Group (HHLWG), of whom 184 from 5 medical centers served as derivation cohort, and 86 cases from 3 other centers served as validation cohort. X-Tile program and Maxstat analysis were used to identify optimal cutoff points of continuous variables; univariate and multivariate Cox analyses were used for variable selection, and the Kaplan-Meier curve was used to analyze the value of variables on prognosis. The C-index, Brier Score, and calibration curve were used for model validation. Multivariate analysis showed that age, creatinine, albumin, platelet, lymphocyte ratio, and alanine aminotransferase were independent prognostic factors. By rounding up the hazard ratios from 6 significant variables, a maximum of 9 points was assigned. The final scoring model of HHLWG-HPI was identified with four risk groups: low risk (≤3 pts), low-intermediate risk (4 pts), high-intermediate risk (5-6 pts), and high risk (≥7 pts), with 5-year overall survival rates of 68.5%, 35.2%, 21.3%, and 10.8%, respectively. The C-indexes were 0.796 and 0.758 in the derivation and validation cohorts by using a bootstrap resampling program. In conclusion, the HHLWG-HPI model provides a feasible and accurate stratification system for individualized treatment strategy in adult HLH.

Clinicopathologic Features and Genomic Signature of De Novo CD5 + Diffuse Large B-Cell Lymphoma : A Multicenter Collaborative Study.

De novo CD5 + diffuse large B-cell lymphoma (DLBCL) has poor survival in the era of immunochemotherapy. Accurate gene-based typing and prognostic stratification can enhance the development of effective individualized treatments. Therefore, we conducted a multicenter retrospective study to evaluate the clinicopathologic characteristics, genomic profiles, and prognostic parameters of 61 patients with CD5 + DLBCL and 60 patients with CD5 - DLBCL, with the goal of facilitating accurate prognostic stratification and potential individualized treatment strategies. Compared with patients with CD5 - DLBCL, older age, advanced stage, higher incidence of central nervous system involvement, and MYC/BCL-2 and p53 overexpression were more prevalent in CD5 + DLBCL. Most patients with CD5 + DLBCL had lymph nodes with non-germinal center B-cell-like or activated B-cell-like subtype according to immunohistochemistry or Lymph2Cx assay. Next-generation sequencing showed that the proportion of MCD subtype (based on the co-occurrence of MYD88 and CD79B mutations) in the CD5 + DLBCL cohort was higher than that in the CD5 - DLBCL cohort (54.2% vs. 13.0%, P =0.005). Compared with the CD5 - cohort, CD5 + DLBCL patients showed poor 5-year overall survival (70.9% vs. 39.0%, P <0.001). Kaplan-Meier survival analysis indicated that cell of origin, MYC/BCL-2, p53, and BCL-6 expression did not have a prognostic impact on patients with CD5 + DLBCL. Multivariate analysis showed that age above 76 years, advanced stage, higher incidence of central nervous system involvement, and hypoalbuminemia were independent factors for poor prognosis in CD5 + DLBCL patients. In summary, CD5 + DLBCL displays poor prognosis, distinctive clinicopathologic characteristics and predominant genetic features of activated B-cell-like and MCD subtypes with worse survival outcome.

LncRNA MNX1-AS1 Contributes to Laryngeal Squamous Cell Carcinoma Growth and Migration by Regulating mir-744-5p/bcl9/ß-Catenin Axis.

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are involved in the progression of laryngeal squamous cell carcinoma (LSCC). Here, we aimed to disclose the role of MNX1-AS1 in LSCC progression, and explore whether MNX1-AS1 participates in LSCC progression via targeting miR-744-5p to active BCL9/ß-catenin signaling. Sixty-five human LSCC tissues and the paracancerous normal tissues were recruited to determine the levels of MNX1-AS1, miR-744-5p and BCL9 using qRT-PCR. The interaction of miR-744-5p and MNX1-AS1/BCL9 was determined by using the RNA immunoprecipitation (RIP) assay and/or luciferase gene reporter assay. Cell viability, in vivo tumor formation, invasion and migration abilities were detected by MTT, Xenograft models and Transwell assays. MNX1-AS1 level was increased significantly in human LSCC tissues as compared with the normal tissues, which showed a positive correlation with BCL9 level while a negative correlation with miR-744-5p level. High level of MNX1-AS1 predicted a poor prognosis and an advanced clinical process in LSCC patients. miR-744-5p targeted upregulation weakened the luciferase activity of MNX1-AS1 and /BCL9, and downregulated their expression levels-wt, while showed no effect when the binding sites were mutated. Knockdown of MNX1-AS1 markedly weakened cell viability, migration, and invasion abilities, while BCL9 overexpression abolished these tendencies. In addition, MNX1-AS1 downregulation induced decreases in tumor volumes and weights in vivo, accompanied by reductions in BCL9, Ki-67 and ß-catenin expression and an increase in miR-744-5p expression. Collectively, this study reveals that MNX1-AS1 contributes to cell growth and migration by regulating miR-744-5p/BCL9/ß-catenin axis in LSCC.

The genetic analysis of Chinese patients with clonal cytopenias using targeted next-generation sequencing.

BACKGROUND: Clonal hematopoiesis (CH) can be found in various myeloid neoplasms (MN), such as myelodysplastic syndromes (MDS), myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN), also in pre-MDS conditions. METHODS: Cytogenetics is an independent prognostic factor in MDS, and fluorescence in-situ hybridization (FISH) can be used as an adjunct to karyotype analysis. In the past 5 years, only 35 of 100 newly diagnosed MDS and MDS/MPN patients were identified abnormalities, who underwent the FISH panel. In addition, we examined a cohort of 51 cytopenic patients suspected MDS or MDS/MPN with a 20-gene next generation sequencing (NGS), including 35 newly diagnosed MN patients and 16 clonal cytopenias of undetermined significance (CCUS) patients. RESULTS: Compared with the CCUS group, the MN group had higher male ratio (22/13 vs 10/6), cytogenetics abnormalities rate (41.4% vs 21.4%) and frequency of a series of mutations, such as ASXL1 (28.6% vs 25%), U2AF1 (25.7% vs 25%), RUNX1 (20% vs 0.0%); also, higher adverse mutations proportion (75% vs 85.2%), and double or multiple mutations (54.3% vs 43.75%). There were 7 MN patients and 4 CCUS patients who experienced cardio-cerebrovascular embolism events demonstrated a significant difference between the two groups (25% vs 20%). Ten of the 11 patients had somatic mutations, half had DNA methylation, while the other half had RNA splicing. Additionally, six patients had disease transformation, and four patients had mutated U2AF1, including two CCUS cases and two MDS-EB cases. Following up to January 2021, there was no significant difference in over survival between the CCUS and MN groups. CONCLUSION: NGS facilitates the diagnosis of unexplained cytopenias. The monitoring and management of CCUS is necessary, also cardio-cerebrovascular embolism events in patients with CH need attention in the clinical practice.

Research progress on treatment of extramedullary multiple myeloma.

ABSTRACTObjectives: Extramedullary multiple myeloma (EMM) is a relatively less frequent subentity of multiple myeloma (MM) and is generally considered to be a poor prognostic factor. Novel agents and hematopoietic stem cell transplantation (HSCT) have led to a significant improvement in the progression-free survival and overall survival of patients with MM, but outcomes of EMM remain dismal. Little is known regarding the role of novel therapies in this setting. This review summarizes the current available data regarding the roles of proteasome inhibitors, immunomodulators, monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapy and HSCT in EMM.Methods: A systematic literature review through PubMed was conducted to summarize the published evidence on the therapeutic developments of novel agents and HSCT in EMM. Literature sources published in English were searched, using the terms multiple myeloma, extramedullary and treatment.Results: Long-term outcomes of EMM patients remain dismal despite the utilization of novel agents and HSCT. The standard therapy of EMM has not been established. EMM should be managed as high-risk disease and treated accordingly.Discussion and conclusion: This review will provide an insight on the current and emerging treatment strategies as well as their efficacy in EMM. Further subgroup analyses in large prospective trials focusing on EMM is needed to help optimize the therapy.