TES and SLC40A1 as Potential Biomarkers for Predicting Survival in T-Cell Acute Lymphoblastic Leukemia.

Introduction: Identifying patients with high-risk T-cell acute lymphoblastic leukemia (T-ALL) is crucial for personalized therapy; however, the lack of robust biomarkers hinders prognosis assessment. To address this issue, our study aimed to screen and validate genes whose expression may serve as predictive indicators of outcomes in T-ALL patients while also investigating the underlying molecular mechanisms.

Methods: Differentially expressed genes (DEGs) between T-ALL patients and healthy controls were identified by integrating data from three independent public datasets.

Comprehensive analysis of human monocyte subsets using full-spectrum flow cytometry and hierarchical marker clustering.

Introduction: Exploring monocytes' roles within the tumor microenvironment is crucial for crafting targeted cancer treatments.

Methods: This study unveils a novel methodology utilizing four 20-color flow cytometry panels for comprehensive peripheral immune system phenotyping, specifically targeting classical, intermediate, and non-classical monocyte subsets.

Results: By applying advanced dimensionality reduction techniques like t-distributed stochastic neighbor embedding (tSNE) and FlowSom analysis, we performed an extensive profiling of monocytes, assessing 50 unique cell surface markers related to a wide range of immunological functions, including activation, differentiation, and immune checkpoint regulation.

Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin α2β1.

Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs.

Outcomes of intermediate or high-risk CMML patients treated with hypomethylating agents combined with venetoclax: A single center experience.

Chronic myelomonocytic leukemia (CMML) treatment remains a pressing clinical challenge. We conducted a retrospective analysis on 52 CMML cases, exploring the effectiveness of combining venetoclax (Vene) with hypomethylating agents (HMAs). The study's findings show promise: the HMAs plus Vene group (n = 13, 53.

Diagnostic and prognostic value of ferroptosis-related genes in patients with Myelodysplastic neoplasms.

This study delves into the emerging role of ferroptosis in Myelodysplastic Neoplasms (MDS) and aims to identify a prognostic ferroptosis-related gene signature for MDS. Utilizing RNA-seq data and clinical information from the Gene Expression Omnibus database, the researchers extracted ferroptosis-related genes from the FerrDb website and conducted differential expression analysis using the 'limma' package in R. Hub ferroptosis-related genes in MDS were screened using the "RandomForest" and "carat" R packages.

Stem cell-based therapy for COVID-19.

While The World Health Organization (WHO) has announced that COVID-19 is no longer a public health emergency of international concern(PHEIC), the risk of reinfection and new emerging variants still makes it crucial to study and work towards the prevention of COVID-19. Stem cell and stem cell-like derivatives have shown some promising results in clinical trials and preclinical studies as an alternative treatment option for the pulmonary illnesses caused by the COVID-19 and can be used as a potential vaccine. In this review, we will systematically summarize the pathophysiological process and potential mechanisms underlying stem cell-based therapy in COVID-19, and the registered COVID-19 clinical trials, and engineered extracellular vesicle as a potential vaccine for preventing COVID-19.

Mesenchymal stem cells reversibly de-differentiate myofibroblasts to fibroblast-like cells by inhibiting the TGF-β-SMAD2/3 pathway.

Background: Myofibroblasts (MFB), one of the major effectors of pathologic fibrosis, mainly derived from the activation of fibroblast to myofibroblast transition (FMT). Although MFBs were historically considered terminally differentiated cells, their potential for de-differentiation was recently recognized and implied with therapeutic value in treating fibrotic diseases, for instance, idiopathic pulmonary fibrosis (IPF) and post allogeneic hematopoietic stem cell transplantation bronchiolitis obliterans (BO). During the past decade, several methods were reported to block or reverse MFB differentiation, among which mesenchymal stem cells (MSC) have demonstrated potential but undetermined therapeutic values.

Targeting Bcl-6 prevents sclerodermatous chronic graft-versus-host disease by abrogating T follicular helper differentiation in mice.

Background: Chronic graft-versus-host disease (cGVHD) is the most common cause of non-relapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). CD4 follicular helper T (Tfh) cells, specialized providers of T cell help to B cells, play a vital role in GVHD pathogenesis. B-cell lymphoma-6 (Bcl-6) transcription factor has been shown to be required for Tfh-mediated germinal center reactions.

Deep learning-based transcriptome model predicts survival of T-cell acute lymphoblastic leukemia.

Identifying subgroups of T-cell acute lymphoblastic leukemia (T-ALL) with poor survival will significantly influence patient treatment options and improve patient survival expectations. Current efforts to predict T-ALL survival expectations in multiple patient cohorts are lacking. A deep learning (DL)-based model was developed to determine the prognostic staging of T-ALL patients.

The Gut Bacteria Dysbiosis Contributes to Chronic Graft-Versus-Host Disease Associated With a Treg/Th1 Ratio Imbalance.

Introduction: Dysbiosis of gut bacteria has been discovered in a large number of autoimmune diseases. However, the influence of the gut bacteria in the mice model of chronic sclerodermatous graft-versus-host disease (Scl-GVHD), a disease that resembles an autoimmune disease characterized by chronic inflammation of multiple organs, such as skin, remains elusive. Here, we explore the role of gut bacteria in an Scl-cGVHD mice model.

Dynamics of PD-1 expression are associated with treatment efficacy and prognosis in patients with intermediate/high-risk myelodysplastic syndromes under hypomethylating treatment.

Hypomethylating agents (HMAs) are widely used in patients with higher-risk MDS not eligible for stem cell transplantation. However, the general response rate by HMAs is lesser than 50% in MDS patients, while the relapse rate is high. Emerging evidence indicates that demethylating effects committed by HMAs may facilitate the up-regulation of a range of immune checkpoints or cancer suppressor genes in patients with MDS, among which the programmed death protein 1 (PD-1) and its ligands are demonstrated to be prominent and may contribute to treatment failure and early relapse.

C3aR costimulation enhances the antitumor efficacy of CAR-T cell therapy through Th17 expansion and memory T cell induction.

Although chimeric antigen receptor (CAR)-modified adoptive T cell therapy is a promising immunotherapy for hematological malignancies, the efficacy improvement in relapsed/refractory acute lymphoblastic leukemia (ALL) with extramedullary infiltration and in multiple myeloma (MM) is still warranted. Since C3aR activation can promote the expansion of tumor-killing Th17 cells, we hypothesized that incorporating C3aR as a costimulatory domain would augment the antitumor activity of CAR-T. In this study, we introduced the C3aR domain into a CAR and generated BB-ζ-C3aR CAR-T targeting CD19 or BCMA.

Loss of PRMT7 reprograms glycine metabolism to selectively eradicate leukemia stem cells in CML.

Our group has reported previously on the role of various members of the protein arginine methyltransferase (PRMT) family, which are involved in epigenetic regulation, in the progression of leukemia. Here, we explored the role of PRMT7, given its unique function within the PRMT family, in the maintenance of leukemia stem cells (LSCs) in chronic myeloid leukemia (CML). Genetic loss of Prmt7, and the development and testing of a small-molecule specific inhibitor of PRMT7, showed that targeting PRMT7 delayed leukemia development and impaired self-renewal of LSCs in a CML mouse model and in primary CML CD34 cells from humans without affecting normal hematopoiesis.

Identification and Validation of a Prognostic Risk-Scoring Model Based on Ferroptosis-Associated Cluster in Acute Myeloid Leukemia.

Emerging evidence has proven that ferroptosis plays an important role in the development of acute myeloid leukemia (AML), whereas the exact role of ferroptosis-associated genes in AML patients' prognosis remained unclear. Gene expression profiles and corresponding clinical information of AML cases were obtained from the TCGA (TCGA-LAML), GEO (GSE71014), and TARGET databases (TARGET-AML). Patients in the TCGA cohort were well-grouped into two clusters based on ferroptosis-related genes, and differentially expressed genes were screened between the two clusters.

miR-204-containing exosomes ameliorate GVHD-associated dry eye disease.

Graft-versus-host disease (GVHD)–associated dry eye disease is characterized by extensive inflammatory destruction in the ocular surface and causes unbearable pain and visual impairment. Current treatments provide limited benefits. Here, we report that exosomes from mesenchymal stromal cells (MSC-exo) administered as eye drops notably alleviate GVHD-associated dry eye disease by suppressing inflammation and improving epithelial recovery in mice and humans.

The novel HLA-A*69:01:04 allele identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-A*69:01:04 differs from HLA-A*69:01:01:01 in exon 2 at position 336 by a single synonymous mutation.

[The Establishment and Identification of Acute Myeloid Leukemia NOD-SCID-IL2rgMice Model by Using Luciferase-Expressing KG1a Cells].

Objective: To establish the in vivo traceable acute myeloid leukemia mice model with Luciferase-Expressing KG1a Cells.

Methods: KG1a cells with stable luciferase gene expression (called as KG1a-Luc cells) were constructed by lentivirus transfection, then sifted out by puromycin. Eighteen male NOD-SCID-IL2rgmice aged 8 to 12 weeks were randomly and equally divided into two groups: the control group and the KG1a-Luc group.

Super-enhancer landscape reveals leukemia stem cell reliance on X-box binding protein 1 as a therapeutic vulnerability.

Relapse of patients with chronic myelogenous leukemia (CML) may occur at least partially because leukemia stem cells (LSCs) lack sensitivity to tyrosine kinase inhibitors (TKIs) such as imatinib. The precise regulation of LSC stemness is incompletely understood. Given that traits of LSCs are subject to epigenetic regulation, we hypothesized that LSCs might be dependent on continuous active transcription of genes associated with super-enhancers (SEs), which might, in turn, suggest an opportunity for intervention.

Bone marrow mesenchymal stromal cells in chronic myelomonocytic leukaemia: overactivated WNT/β-catenin signalling by parallel RNA sequencing and dysfunctional phenotypes.

Sophisticated cross-talk between bone marrow mesenchymal stromal cells (BM MSCs) and haematopoietic/leukaemic stem cells in patients with myelodysplastic syndromes (MDS) and myeloid leukaemia have been emphasized in previous reports. However, mesenchymal elements in patients with chronic myelomonocytic leukaemia (CMML) were poorly investigated. By utilizing a parallel RNA-sequencing method, we investigated the transcriptional profile and functional defects of primary BM MSCs from patients with CMML for the first time.

Targeting protein lysine methyltransferase G9A impairs self-renewal of chronic myelogenous leukemia stem cells via upregulation of SOX6.

The application of tyrosine kinase inhibitors (TKIs) in clinic has revolutionized chronic myelogenous leukemia (CML) treatment, but fails to eliminate leukemia stem cells (LSCs), which are considered as roots of drug resistance and disease relapse. Thus, eradication of LSCs may be a promising strategy for curing CML. In this study, we found that protein lysine methyltransferase G9A was overexpressed in CML LSCs.

C-Type Lectin-Like Molecule-1 as a Biomarker for Diagnosis and Prognosis in Acute Myeloid Leukemia: A Preliminary Study.

Objective: AML is a heterogeneous disease both in genomic and proteomic backgrounds, and variable outcomes may appear in the same cytogenetic risk group. Therefore, it is still necessary to identify new antigens that contribute to diagnostic information and to refine the current risk stratification.

Methods: The expression of C-type lectin-like molecule-1 (CLL-1) in AML blasts was examined in 52 patients with newly diagnosed or relapsed/refractory AML and was compared with two other classic markers CD33 and CD34 in AML, in order to assess the value of CLL-1 as an independent biomarker or in combination with other markers for diagnosis in AML.

Challenges and advances in clinical applications of mesenchymal stromal cells.

Mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have been intensely investigated for clinical applications within the last decades. However, the majority of registered clinical trials applying MSC therapy for diverse human diseases have fallen short of expectations, despite the encouraging pre-clinical outcomes in varied animal disease models. This can be attributable to inconsistent criteria for MSCs identity across studies and their inherited heterogeneity.

IL-6 trans-signaling promotes the expansion and anti-tumor activity of CAR T cells.

Chimeric antigen receptor (CAR) T cell therapies lead to high clinical response rates in B cell malignancies, and are under investigation for treatment of solid tumors. While high systemic interleukin- (IL-) 6 levels are associated with clinical cytokine release syndrome (CRS), the role of IL-6 trans-signaling within CAR T-cells has not been reported. We generated CAR T cells that constitutively express hyper IL-6 (HIL-6), a designer cytokine that activates the trans-signaling pathway.