The KIR2DL family serves as prognostic biomarkers and correlates with immune infiltrates in acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a prevalent haematological malignancy in which various immune and stromal cells in the bone marrow microenvironment have instrumental roles and substantially influence its progression. KIR2DL is a member of the immunoglobulin-like receptor family and a natural killer (NK) cell surface-specific receptor. However, its impact on immune infiltration regarding AML has not been addressed. We aimed to explore molecular markers associated with the immune microenvironment and prognosis of AML with a particular focus on KIR2DL family members. Analysis of data from The Cancer Genome Atlas and Genotype-Tissue Expression databases revealed that KIR2DL1, KIR2DL3 and KIR2DL4 expression were significantly upregulated in AML and associated with decreased overall survival (OS). Moreover, univariate Cox analysis implicated KIR2DL genes as independent prognostic markers of OS. Functional enrichment analysis revealed that KIR2DL genes were associated with immune cells, the immune microenvironment and NK cell-mediated cytotoxicity. Additionally, immune infiltration analyses revealed that KIR2DL upregulation was associated with stronger immune infiltration. Finally, we performed drug sensitivity profiling of KIR2DL genes using the Cellminer database. Collectively, our findings suggest that KIR2DL1, KIR2DL3 and KIR2DL4 have critical roles in AML and may represent novel biomarker genes for disease prognosis and immune infiltration.

Mechanism of salidroside regulating autophagy based on network pharmacology and molecular docking.

Salidroside is a natural product of phenols with a wide range of pharmacological functions, but whether it plays a role in regulating autophagy is unclear. We systematically investigated the regulatory effect and molecular mechanism of salidroside on autophagy through network pharmacology, which provided a theoretical basis for subsequent experimental research. First, the target genes of salidroside were obtained using the Chinese Medicine System Pharmacology Database and Analysis Platform, and the target genes were converted into standardized gene names using the Uniprot website. At the same time, autophagy-related genes were collected from GeneCards, and preliminary handling of data to obtain intersecting genes. Then, the String website was used to construct a protein-protein interaction network, and to perform the Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis. To observe the specific molecular mechanism by which salidroside regulates autophagy, we constructed a drug component-target genes-autophagy network. Finally, we performed molecular docking to verify the possible binding conformation between salidroside and the candidate target. By searching the database and analyzing the data, we found that 113 target genes in salidroside interact with autophagy. Salidroside regulate autophagy in relation to a number of important oncogenes and signaling pathways. Molecular docking confirmed that salidroside has high affinity with mTOR, SIRT1, and AKT1. Through network pharmacology combined with molecular docking-validated research methods, we revealed the underlying mechanism of salidroside regulation of autophagy. This study not only provides new systematic insights into the underlying mechanism of salidroside in autophagy, but also provides new ideas for network approaches for autophagy-related research.

[Research Progress of NK Cell Therapy in Multiple Myeloma Treatment --Review].

Multiple myeloma (MM) is a hematologic neoplasm characterized by malignant proliferation of monoclonal plasma cells in the bone marrow. NK cells, a class of innate lymphocytes with potent natural killer activity, are capable of recognizing and destroying tumor cells and virally infected cells, and have attracted attention as a potential anticancer therapy. In patients with MM, NK cells are suppressed in number and function, resulting in reduced immune surveillance and clearance of myeloma cells. Restoring or enhancing the killing effect of NK cells on myeloma cells is an important strategy for MM immunotherapy, and some progress has been made in clinical trials targeting NK cellrelated therapies. This article reviews the research progress on the applications prospects of NK cell in MM immunotherapy.

EV-mediated intercellular communication in acute myeloid leukemia: Transport of genetic materials in the bone marrow microenvironment.

Acute myeloid leukemia (AML) is a common hematological cancer. Cancer cells exchange information with the surrounding microenvironment, which can be transmitted by extracellular vesicles (EVs). In recent years, the genetic materials transported by EVs have attracted attention due to their important roles in different pathological processes. EV-derived ncRNAs (EV-ncRNAs) regulate physiological functions and maintain homeostasis, mainly including microRNAs, long noncoding RNAs, and circular RNAs. However, the mechanism of involvement and potential clinical application of EV-ncRNAs in AML have not been reported. Given the unique importance of the bone marrow microenvironment (BMME) for AML, a greater understanding of the communication between leukemic cells and the BMME is needed to improve the prognosis of patients and reduce the incidence of recurrence. Additionally, studies on leukemic EV-ncRNA transport guide the design of new diagnostic and therapeutic tools for AML. This review systematically describes intercellular communication in the BMME of AML and emphasizes the role of EVs. More importantly, we focus on the information transmission of EV-ncRNAs in the BMME to explore their clinical application as potential biomarkers and therapeutic targets.

Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study.

BACKGROUND: Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, has shown encouraging anti-tumour activity in heavily pre-treated patients with relapsed or refractory peripheral T-cell lymphoma in a phase 1 study (JACKPOT8 Part A). Here, we report the full analysis of a phase 2 study, in which we assessed the anti-tumour activity of golidocitinib in a large multinational cohort of patients. METHODS: We did a single-arm, multinational, phase 2 trial (JACKPOT8 Part B) in 49 centres in Australia, China, South Korea, and the USA. Eligible patients were adults (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were given oral golidocitinib 150 mg once daily until disease progression or other discontinuation criteria were met. The primary endpoint was the CT-based objective response rate, assessed by an independent review committee (IRC) per Lugano 2014 classification. The activity analysis set included all patients who received at least one dose and whose pathological diagnosis of peripheral T-cell lymphoma had been retrospectively confirmed by a central laboratory and who had at least one measurable lesion at baseline assessed by IRC. The safety analysis set included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04105010, and is closed to accrual and follow-up is ongoing. FINDINGS: Between Feb 26, 2021, and Oct 12, 2022, we assessed 161 patients for eligibility, of whom 104 (65%) were enrolled and received at least one dose of study drug; the activity analysis set included 88 (85%) patients (median age 58 years [IQR 51-67], 57 [65%] of 88 were male, 31 [35%] were female, and 83 [94%] were Asian). As of data cutoff (Aug 31, 2023; median follow-up was 13·3 months [IQR 4·9-18·4]), per IRC assessment, the objective response rate was 44·3% (95% CI 33·7-55·3; 39 of 88 patients, p<0·0001), with 21 (24%) patients having a complete response and 18 (20%) having a partial response. In the safety analysis set, 61 (59%) of 104 patients had grade 3-4 drug-related treatment-emergent adverse events. The most common grade 3-4 drug-related treatment-emergent adverse events were neutrophil count decreased (30 [29%]), white blood cell count decreased (27 [26%]), lymphocyte count decreased (22 [21%]), and platelet count decreased (21 [20%]), which were clinically manageable and reversible. 25 (24%) patients had treatment-related serious adverse events. Deaths due to treatment-emergent adverse events occurred in three (3%) patients: two (2%) due to pneumonia (one case with fungal infection [related to golidocitinib] and another one with COVID-19 infection) and one (1%) due to confusional state. INTERPRETATION: In this phase 2 study, golidocitinib showed a favourable benefit-risk profile in treating relapsed or refractory peripheral T-cell lymphoma. The results of this study warrant further randomised clinical studies to confirm activity and assess efficacy in this population. FUNDING: Dizal Pharmaceutical.

[Research Progress of Cancer-associated Fibroblasts in Hematolo- gic Malignancies --Review].

Cancer-associated fibroblasts （CAF） are a key component of the tumor microenvironment, which can secrete a variety of cytokines, chemokines and growth factors, directly and indirectly support cancer cells, also alter the immune cellular environment by inhibiting the activity of immune effector cells and recruiting immunosuppressive cells, thereby allowing cancer cells to evade immune surveillance. CAF has been proven to be associated with the development, progression, and poor prognosis of solid tumors. However, the role of CAF in hematological malignancies is still unclear. This article reviews the research progress of CAF in hematological malignancies.

Identifying a prognostic model and screening of potential natural compounds for acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is one of the most common hematologic malignancies with a poor prognosis and high recurrence rate. The discovery of new predictive models and therapeutic agents plays a crucial role. Methods: The differentially expressed gene that was explicitly highly expressed in The Cancer Genome Atlas (TCGA) and GSE9476 transcriptome databases were screened and included in the least absolute shrinkage and selection operator (LASSO) regression model to derive risk coefficients and build a risk score model. Functional enrichment analysis was conducted on the screened hub genes to explore the potential mechanisms. Subsequently, critical genes were incorporated into a nomogram model based on risk scores to analyze prognostic value. Finally, this study combined network pharmacology to find potential natural compounds for hub genes and used molecular docking to verify the binding ability of molecular structures to natural compounds to explore drug development for possible efficacy in AML. Results: A total of 33 highly expressed genes may be associated with poor prognosis of AML patients. After LASSO and multivariate Cox regression analysis of 33 critical genes, Rho-related BTB domain containing 2 (RHOBTB2), phospholipase A2 (PLA2G4A), interleukin-2 receptor-α (IL2RA), cysteine and glycine-rich protein 1 (CSRP1), and olfactomedin-like 2A (OLFML2A) were found to played a significant role in the prognosis of AML patients. CSRP1 and OLFML2A were independent prognostic factors of AML. The predictive power of these 5 hub genes in combination with clinical features was better than clinical data alone in predicting AML in the column line graphs and had better predictive value at 1, 3, and 5 years. Finally, through network pharmacology and molecular docking, this study found that diosgenin in Guadi docked well with PLA2G4A, beta-sitosterol in Fangji docked well with IL2RA, and OLFML2A docked well with 3,4-di-O-caffeoylquinic acid in Beiliujinu. Conclusions: The predictive model of RHOBTB2, PLA2G4A, IL2RA, CSRP1, and OLFML2A combined with clinical features can better guide the prognosis of AML. In addition, the stable docking of PLA2G4A, IL2RA, and OLFML2A with natural compounds may provide new options for treating AML.

The non-coding competing endogenous RNAs in acute myeloid leukemia: biological and clinical implications.

Acute myeloid leukemia (AML) is a hematologic carcinoma that has seen a considerable improvement in patient prognosis because of genetic diagnostics and molecularly-targeted therapies. Nevertheless, recurrence and drug resistance remain significant obstacles to leukemia treatment. It is critical to investigate the underlying molecular mechanisms and find solutions. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), circular RNAs, long non-coding RNAs, and pseudogenes, have been found to be crucial components in driving cancer. The competing endogenous RNA (ceRNA) mechanism has expanded the complexity of miRNA-mediated gene regulation. A great deal of literature has shown that ncRNAs are essential to the biological functions of the ceRNA network (ceRNET). NcRNAs can compete for the same miRNA response elements to influence miRNA-target RNA interactions. Recent evidence suggests that ceRNA might be a potential biomarker and therapeutic strategy. So far, however, there have been no comprehensive studies on ceRNET about AML. What is not yet clear is the clinical application of ceRNA in AML. This study attempts to summarize the development of research on the related ceRNAs in AML and the roles of ncRNAs in ceRNET. We also briefly describe the mechanisms of ceRNA and ceRNET. What's more significant is that we explore the clinical value of ceRNAs to provide accurate diagnostic and prognostic biomarkers as well as therapeutic targets. Finally, limitations and prospects are considered.

Mechanism of Procyanidin B2 in the Treatment of Chronic Myeloid Leukemia Based on Integrating Network Pharmacology and Molecular Docking.

OBJECTIVE: To study the pharmacological mechanism of procyanidin B2 (PCB2) on chronic myeloid leukemia (CML) by integrating network pharmacological methods systematically. METHODS: Firstly, the potential target genes of PCB2 were predicted by the pharmacological database and analysis platform (TCMSP and Pharmmapper). Meanwhile, the relevant target genes of CML were collected from GeneCards and DisGene. Pooled data were collected to screen for common target genes. Furthermore, the above intersection genes were imported into the String website to construct a protein-protein interaction (PPI) network, and the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were further analyzed. Besides, molecular docking was performed to verify the possible binding conformation between PCB2 and candidate targets. Finally, MTT and RT-PCR experiments of K562 cells were performed to verify the above results of network pharmacology. RESULTS: A total of 229 PCB2 target genes were retrieved, among which 186 target genes had interaction with CML. The pharmacological effects of PCB2 on CML were related to some important oncogenes and signaling pathways. The top ten core targets predicted by Network Analysis were as follows: AKT1, EGFR, ESR1, CASP3, SRC, VEGFA, HIF1A, ERBB2, MTOR, and IGF1. Molecular docking studies confirmed that hydrogen bonding was the main interaction force of PCB2 binding targets. According to the molecular docking score, the following three target proteins were most likely to bind to PCB2: VEGFA (-5.5 kcal/mol), SRC (-5.1 kcal/mol), and EGFR (-4.6 kcal/mol). After treatment of PCB2 for 24h, mRNA expression levels of VEGFA and HIF1A decreased significantly in K562 cells. CONCLUSION: Through integrating network pharmacology combined with molecular docking, the study revealed the potential mechanism of PCB2 anti-chronic myeloid leukemia.

[Recent Research Progress of Extramedullary Plasmacytoma --Review].

Extramedullary plasma cell tumor (EMP) is a kind of plasma cell tumor, and its pathogenesis is not completely clear. According to whether it is independent of myeloma disease, it can be divided into primary and secondary EMP, which have different biological and clinical characteristics. Primary EMP has low invasion, fewer cytogenetic and molecular genetic abnormalities and good prognosis, and surgery and / or radiotherapy are the mainly treatments. Secondary EMP, as the extramedullary invasive progression of multiple myeloma (MM), is often accompanied by high-risk cellular and molecular genetic abnormalities and poor prognosis, chemotherapy, immunotherapy and hematopoietic stem cell transplantation are the mainly treatment. This paper reviews the latest research progress of EMP in the pathogenesis, cytogenetics molecular genetics and treatment, so as to provide reference for clinical work.

Mechanism of salidroside in the treatment of chronic myeloid leukemia based on the network pharmacology and molecular docking.

BACKGROUND: Salidroside is a phenolic natural product, which is a kind of Rhodiola rosea. It has been confirmed that it has inhibitory effects on chronic myeloid leukemia, but the specific performance of its molecular effects is still unclear. OBJECTIVE: To systematically study the pharmacological mechanism of salidroside on chronic myeloid leukemia by means of network pharmacology. METHODS: First, the possible target genes of salidroside were predicted through the Traditional Chinese Medicine Pharmacology Database and Analysis Platform, the target gene names were converted into standardized gene names using the Uniprot website. At the same time, the related target genes of chronic myeloid leukemia were collected from GeneCards and DisGenet; Collect summary data and screen for commonly targeted genes. Then, the above-mentioned intersected genes were imported into the String website to construct the protein-protein interaction (PPI) network, and the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were further analyzed. To investigate the overall pharmacological effects of salidroside on chronic myeloid leukemia, we constructed a drug component-target gene-disease (CTD) network. Finally, molecular docking was performed to verify the possible binding conformation between salidroside and the candidate target. RESULTS: A total of 126 salidroside target genes were retrieved, and 106 of them had interactions with chronic myeloid leukemia. The pharmacological effects of salidroside on chronic myeloid leukemia are related to some important oncogenes and signaling pathways. Molecular docking studies confirmed that the main role of salidroside binding to the target genes is hydrogen bonding. CONCLUSIONS: We revealed the potential mechanism of action of salidroside against chronic myeloid leukemia, verified by network pharmacology combined with molecular docking. However, salidroside is a promising drug for the prevention and treatment of chronic myeloid leukemia, and further research is needed to prove it.

[Mechanism Underlying the Inhibitory Effect of MiR-532-3p on the Cells Proliferation of Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the effects and underlying mechanism of miR-532-3p and resibufogenin (RES) by regulating Wnt/ß-catenin signaling on diffuse Large B-cell lymphoma (DLBCL) cells proliferation. METHODS: DLBCL tissues and adjacent normal tissues were collected from patients had been diagnosed with DLBCL at the First Hospital of Lanzhou University from October 2019 to October 2021. Four groups including mimics-NC, miR-532-3p mimics, RES control and RES treatment in SU-DHL-4 cells were designed. The expression level of miR-532-3p was detected by RT-qPCR. The protein content of ß-catenin was detected by Western blot. MTT assay was used to detect the proliferation activity of SU-DHL-4 cells. RESULTS: miR-532-3p expression was significantly decreased in DLBCL tissues compared with adjacent normal tissues (P<0.001). The miR-532-3p content in lymphoma cells was significantly lower than that in normal lymphocytes (P<0.001). After overexpression of miR-532-3p, the viability of SU-DHL 4 cells was significantly decreased (P<0.001), with a reduced expression of ß-catenin (P<0.05). RES treatment inhibited the proliferation of SU-DHL-4 cells and decreased ß-catenin expression in SU-DHL-4 cells compared with the control group. CONCLUSION: Overexpression of miR-532-3p reduced Wnt/ß-catenin signaling and inhibited the proliferation of lymphoma cells. Moreover, RES treatment inhibited lymphoma cells growth partially through Wnt/ß-catenin signaling suppression.

Comparison of efficacy and safety of ripertamab (SCT400) versus rituximab (Mabthera® ) in combination with CHOP in patients with previously untreated CD20-positive diffuse large B-cell lymphoma: A randomized, single-blind, phase III clinical trial.

This study compared the efficacy, safety and immunogenicity of ripertamab (SCT400) and rituximab (Mabthera® ) combined with CHOP as the first-line treatment for Chinese patients with CD20-positive diffuse large B cell lymphoma (DLBCL). This is a randomized, patient-blind, multicenter, active-control, non-inferiority study with parallel design. Patients were randomly (2:1) to receive ripertamab combined with CHOP (S-CHOP) or rituximab (Mabthera® ) combined with CHOP (R-CHOP) for up to 6 cycles. The primary endpoint was the Independent Review Committee (IRC) assessed objective response rate (ORR) in full analysis set (FAS) and the per protocol set (PPS). A total of 364 patients (243 in the S-CHOP and 121 in the R-CHOP groups) were enrolled in this study. In FAS, IRC-assessed ORRs were 93.8% (95% confidence interval (CI) 90.0%, 96.5%) and 94.2% (95% CI: 88.4%, 97.6%) in the S-CHOP and R-CHOP groups (p = 0.9633), respectively. The ORR difference between the two groups -0.4% (95% CI: -5.5%, 4.8%) met the pre-specified non-inferiority margin of -12%. There were no significant differences between the S-CHOP and R-CHOP groups in 1-year progression-free survival rates (81.1% vs. 83.2%, p = 0.8283), 1 year event-free survival rates (56.2% vs. 58.1%, p = 0.8005), and 3-year overall survival rates (81.0% vs. 82.8%, p = 0.7183). The results in PPS were consistent with those in FAS. The rates of treatment-emergent adverse events (TEAEs) and ≥ grade 3 TEAEs were 97.9% and 99.2%, 85.2% and 86.0% in the S-CHOP and R-CHOP groups, respectively in safety set. The percentage of anti-drug antibodies positive patients in the S-CHOP group was numerically lower than the R-CHOP group (10.9% vs. 16.0%). This study demonstrated that S-CHOP was not inferior to R-CHOP in the first-line treatment of Chinese patients with CD20-positive DLBCL in efficacy, safety and immunogenecity. S-CHOP could be an alternative first-line standard treatment regimen for this patient population.

[Expression and Prognostic Value of Metabolism-related Genes in Pediatric Acute Lymphoblastic Leukemia].

OBJECTIVE: To analyze the expression and prognostic value of metabolism-related genes in pediatric acute lymphoblastic leukemia (ALL), and explore the potential prognostic biomarkers or therapeutic targets. METHODS: Transcriptome data from 84 children with B-cell ALL at the time of diagnosis and prior to any treatment were used to analyze the differential gene expression. A prognostic scoring system based on the expression of the metabolism-related genes was constructed using Cox and Lasso regression methods. The prognostic value of the scoring system was further assessed by multivariate Cox regression analysis. Gene set enrichment analysis was carried out by using GSEA software. RESULTS: Among the 933 metabolism-related genes, 14 up-regulated genes and 17 down-regulated genes were identified as differentially expressed genes. In addition, 8 up-regulated genes (ASS1, CKM, PTGES, ADCY5, HNMT, PHGDH, CYP4F3, AADAT) and 4 down-regulated genes (GDA, DHRS9, IDO2, UGT2B4) were selected to establish a novel prognostic scoring system. Patients in the high-risk group showed poorer survival significantly than patients in the low-risk group (P<0.05). The prognostic scoring system was still shown to be an independent prognostic factor for the survival of children with ALL after the clinical characteristics, such as gender, age, white blood cell count at initial diagnosis, cytogenetics and molecular genetics were included (HR=8.906, 95%CI: 3.114-25.470). GSEA results showed that 6 metabolism-related pathways (amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, fructose and mannose metabolism, glyoxylate and dicarboxylate metabolism, pyrimidine metabolism, selenoamino acid metabolism) were enriched in the high-risk group. CONCLUSION: The abnormal metabolism-related gene expression is associated with the clinical outcome of children with ALL, and these results provide potential novel prognostic biomarkers and treatment targets for pediatric ALL.

[The Relationship between Body Mass Index and Adult Acute Myeloid Leukemia].

OBJECTIVE: To analysis the relationship between different BMI (body mass index) and the clinical characteristics, laboratory examination indexes of newly diagnosed adult patients with acute myeloid leukemia (AML), so as to investigate the effects of BMI to the efficacy of first induction chemotherapy. METHODS: The clinical data of 145 newly diagnosed adult AML patients treated in the First Hospital of Lanzhou University from August 2015 to August 2019 were retrospective analyzed. According to the guidelines for prevention and control of overweight and obesity in Chinese adults, the BMI (kg/m2) of the selected AML patients before induction chemotherapy was calculated and the patients were divided into the low body mass group (BMI<18.5), the normal body mass group (18.5 ≤BMI ≤23.9) and the overweight and obese group (BMI ≥24). The clinical data of the patients, including sex, age, risk stratification,the types of leukemia, gene mutation, complications, length of hospital stay and other clinical features; white blood cell (WBC), hemoglobin (Hb), albumin, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low density lipoprotein (LDL), lactate dehydrogenase (LDH), and other laboratory index; agra-nulocytosis with fever, infection of etiology, lack of granulocyte duration, significant bleeding, liver and kidney toxicity of chemotherapy adverse reactions associated indicators and Morphological remission were collected. The induction chemotherapy regimen was the standard chemotherapy regimen (anthracyclines combined with cytarabine). RESULTS: Among the 145 newly diagnosed adult AML patients, there were 71 males and 74 females. The median age was 50 years old(range 18 to 82 years old). There were 21 patients in underweight group (14.5%), 79 patients in normal weight group (54.5%), and 45 patients in overweight and obese group (31.0%). The patients with higher BMI level showed the older in age（P=0.018）. There were significant differences in sex between the patients in each group(P=0.035). In overweight and obese patients, the number of male was significantly higher than female. There were no statistical differences in AML classification, comorbidities(Diabetes, hypertension, coronary heart disease), hospital days, whether secondary AML and FLT3 gene mutation among the patients in different BMI groups. There were significant differences in TG of the patients in the different groups, the overweight and obese patients were higher (P=0.007). There were no significant differences in WBC and Hb counts, ALB, TC, HDL, LDL, or LDH between the patients in each BMI group at newly diagnosed. The complete remission rate of the patients in the low body mass group or overweight and obese group were lower than that in the normal body weight group (P=0.035). The rate of documented infection during the first induction chemotherapy were significantly higher for the patients in low body mass group than those in normal weight group or overweight and obese group (P=0.038). There was no statistical difference in chemotherapy regimens, the number of chemotherapy until CR, febrile neutropenia, bleeding, and the time of neutropenia, liver and kidney toxicity among each BMI group. Multivariate analysis showed that overweight and obese (P=0.012) , FLT3 mutation (P=0.015) were the risk factors affecting the CR rate of the patients. And the patients with secondary AML, high-risk type, and newly diagnosed WBC ≥50×109/L showed lower CR rate, but there was no statistical difference in the patients of each group. CONCLUSION: In newly diagnosed adult patients with AML, low body mass, overweight and obesity, and FLT3 mutations were the factors reducing the early efficacy of AML patients. There were more adverse reactions induced by chemotherapy in the low body mass group. Therefore, inappropriate BMI level can be a risk factor for assessing the prognosis of adults with newly diagnosed AML.

Higher red blood cell distribution width at diagnose is a simple negative prognostic factor in chronic phase-chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: A retrospective study.

ABSTRACT: The aim of this study was to evaluate the ability of the red blood cell distribution width (RDW) to predict prognosis and treatment response in chronic myeloid leukemia (CML)-chronic phase (CP) patients treated with tyrosine kinase inhibitor (TKIs).We retrospectively enrolled 93 newly diagnosed CML-CP patients treated with TKIs from 2009 to 2018 at the First Hospital of Lanzhou University. Patients were divided into 2 groups using an RDW of 18.65% determined by receiver operating characteristic curve analysis. We analyzed the correlation of treatment responses and the RDW compared to common scoring systems, as well as the correlation of the RDW with disease outcome, including overall survival (OS) and progression-free survival (PFS), and demographic and laboratory factors affecting outcome. Univariate analysis and Cox regression analysis were used.The median age of patients was 40 years, and 51 patients (54.8%) were men. A high RDW could predict treatment response at 3 months (P = .03) and 6 months (P = .02). The RDW was significantly lower in patients who achieved molecular response by 3 months (P < .001) and complete cytogenetic response by 6 months (P = .001) than in those who did not respond. Patients with a high RDW (>18.65%, n = 35) had significantly worse 5-year OS (77.1% vs 96.6%; P = .008) and PFS (80.0% vs 98.3%; P = .002) than those with a low RDW (≤18.65%, n = 58). Multivariate analysis demonstrated that a high RDW was an adverse predictor of OS (P = .005, HR (hazard ratio) = 9.741) and PFS (P = .009, HR = 16.735).The RDW is a readily available prognostic marker of outcome in patients with CML-CP and can predict treatment response to TKIs. Further larger and prospective studies are required.

Identification of mast cells as a candidate significant target of immunotherapy for acute myeloid leukemia.

OBJECTION: Immunotherapy based on T cells is a new therapy for Acute myeloid leukemia (AML). However, there has not been considerable improvement compared with traditional chemotherapeutics. This study aimed to identify important immune cells, genes, and drugs associated with the immunotherapy of AML. METHODS: The gene expression profile and clinical data of patients with AML were downloaded from TCGA database, and the abundance ratio of immune cells was obtained via CIBERSORT. Kaplan-Meier (KM) survival analysis was used to assess the relationship between immune cells and survival time of patients with AML. Differentially expressed genes (DEGs) analysis was conducted to obtained DEGs related to mast cells. Then, protein-protein interaction (PPI) analysis and enrichment analysis were performed to explore the hub genes. Finally, Connectivity Map (CMap) database was utilized to predicts potential drugs that may reverse or induce the mast cell-related gene expression. RESULTS: Our study showed that mast cell was correlated with survival time of patients with AML, and 135 genes were screened to be related with mast cells. 6 hub genes were identified via PPI network, and 3 potential small molecule drugs were screened to be related to regulating the mast cell-related gene expression via CMap database. CONCLUSION: The hub genes and drugs have high research value and clinical application in AML therapy. Our study not only provides gene targets and small molecule drugs for AML immunotherapy concerning mast cells but also provides new ideas for researchers to explore immunotherapy targets of other tumors.

Efficacy and safety of geptanolimab (GB226) for relapsed or refractory peripheral T cell lymphoma: an open-label phase 2 study (Gxplore-002).

BACKGROUND: Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. METHODS: We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria. RESULTS: Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30-22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2-51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to < 50% ones (ORR, 53.3% vs. 25.0%, p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related. CONCLUSIONS: In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population. TRIAL REGISTRATION: This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.

Occult olfactory neuroblastoma presenting with multiple bone metastases: a case report.

RATIONABLE: Olfactory neuroblastoma (ONB) is a rare malignant tumor of the nasal cavity, the primary local symptoms are usually inconspicuous. Patients are often admitted to various specialties based on different primary symptoms, which may result in delayed diagnosis and even a misdiagnosis. PATIENT CONCERNS: Here we report a case of ONB that presented initially as multiple ostealgia without any local symptoms of the tumor and primarily misdiagnosed as multiple myeloma. The patient was a 47-year-old female with bone pain at multiple sites. The initial diagnosis was considered as multiple myeloma. However, the morphologic examination of bone marrow suggested that the tumor cells originated from the nervous tissues. After the positron emission computed tomography scan, the primary lesion in the nasal cavity was located, and a biopsy was performed. DIAGNOSIS: The final diagnosis of ONB was confirmed by histopathological tests. INTERVENTIONS: The patient was treated with metronomic chemotherapy. OUTCOMES: The symptoms of bone pain were significantly relieved 3 months later. The emission computed tomography scan of the whole body bones and the magnetic resonance imaging of the head showed that the tumor size did not change significantly and proved a progression-free of the disease. LESSONS: It is a reasonable strategy to identify the original latent tumor by a prompt positron emission computed tomography scan when the primary diagnosis indicates a metastatic disease, especially for the occult malignancies like ONB.