Leukemia expression

BACKGROUND: Methylprednisolone (MP) is a pharmaceutical agent employed in the management of Leukemia, which is a systemic malignancy that arises from abnormalities in the hematological system. Numerous investigations in the field of cancer research have directed their attention towards propolis, a natural substance with significant potential as a treatment-supportive agent. Its utilization aims to mitigate the potential adverse effects associated with chemotherapy medications. The objective of this study was to examine the impact of olive oil-based propolis (OEP) and caffeic acid phenethyl ester (CAPE) on the treatment of acute myeloid leukemia, as well as to determine if they exhibit a synergistic effect when combined with the therapeutic support product methylprednisolone...

Acute Myeloid Leukemia (AML) is a malignant blood cancer with a high mortality rate. Neutrophil extracellular traps (NETs) influence various tumor outcomes. However, NET-related genes (NRGs) in AML had not yet received much attention. This study focuses on the role of NRGs in AML and their interaction with the immunological microenvironment. The gene expression and clinical data of patients with AML were downloaded from the TCGA-LAML and GEO cohorts. We identified 148 NRGs through the published article. Univariate Cox regression was used to analyze the association of NRGs with overall survival (OS)...

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common among children. AML is characterized by aberrant proliferation of myeloid blasts in the bone marrow and impaired normal hematopoiesis. Despite the introduction of new drugs and allogeneic bone marrow transplantation, patients have poor overall survival rate with relapse as the major challenge, driving the demand for new therapeutic strategies. AML patients with high expression of the very long/long chain fatty acid transporter CD36 have poorer survival and very long chain fatty acid metabolism is critical for AML cell survival...

OBJECTIVES: Intimal hyperplasia is a serious clinical problem associated with the failure of therapeutic methods in multiple atherosclerosis-related coronary heart diseases, which are initiated and aggravated by the polarization of infiltrating macrophages. The present study aimed to determine the effect and underlying mechanism by which tumor necrosis factor receptor-associated factor 5 (TRAF5) regulates macrophage polarization during intimal hyperplasia. METHODS: TRAF5 expression was detected in mouse carotid arteries subjected to wire injury...

Innovative strategies to enhance efficacy and overcome drug resistance in hematologic cancers such as antibody-drug conjugates (ADCs) have shifted the paradigm of conventional care by delivering promising outcomes in cancer therapies with a significant reduction in the risk of relapse. The transferrin receptor 1, CD71, known to be overexpressed in malignant cells, is considered a potent anti-tumoral target. Therefore, we have developed an anti-CD71 ADC, INA03, a humanized antibody conjugated to the monomethyl auristatin E (MMAE) through a 3-arylpropiolonitrile-valine-citruline linker...

Solute carrier family 27 member 2 (SLC27A2) is involved in fatty acid metabolism in tumors and represents a prospective target for cancer therapy. However, the role and mechanism of action of SLC27A2 in acute lymphoblastic leukemia (ALL) remain unclear. In this study, we aimed to explore the intrinsic associations between SLC27A2 and ALL and evaluate the prognostic significance, biological functions, and correlation with immune infiltration. We used the transcriptome and clinical data from the TARGET dataset...

Acute myeloid leukemia (AML) is a hematopoietic malignancy with a high relapse rate and progressive drug resistance. Alternative polyadenylation (APA) contributes to post-transcriptional dysregulation, but little is known about the association between APA and AML. The APA quantitative trait locus (apaQTL) is a powerful method to investigate the relationship between APA and single nucleotide polymorphisms (SNPs). We quantified APA usage in 195 Chinese AML patients and identified 4922 cis-apaQTLs related to 1875 genes, most of which were newly reported...

Risk stratification using genetics and minimal residual disease (MRD) has allowed to increase the cure rates of pediatric acute myeloid leukemia (pedAML) up to 70% in contemporary protocols. Nevertheless, approximately 30% of patients still experience relapse, indicating a need to optimize stratification strategies. Recently, long non-coding RNA (lncRNA) expression has been shown to hold prognostic power in multiple cancer types. Here, we aimed at refining relapse prediction in pedAML using lncRNA expression...

Chronic antigen stimulation is thought to generate dysfunctional CD8 T cells. Here, we identify a CD8 T cell subset in the bone marrow tumor microenvironment that, despite an apparent terminally exhausted phenotype (TPHEX ), expressed granzymes, perforin, and IFN-γ. Concurrent gene expression and DNA accessibility revealed that genes encoding these functional proteins correlated with BATF expression and motif accessibility. IFN-γ+ TPHEX effectively killed myeloma with comparable efficacy to transitory effectors, and disease progression correlated with numerical deficits in IFN-γ+ TPHEX ...

B-cell Chronic Lymphocytic Leukemia (B-CLL) is a malignancy caused by the clonal expansion of mature B lymphocytes bearing a CD5+ CD19+ (B1) phenotype. However, the origin of B-CLL remains controversial. We showed previously that STYK1/NOK transgenic mice develop a CLL-like disease. Using this model system in this study, we attempt to define the stage of CLL initiation. Here, we show that the phenotype of STYK1/NOK-induced B-CLL is heterogeneous. The expanded B1 lymphocyte pool was detected within peripheral lymphoid organs and was frequently associated with the expansions of memory B cells...

This study aims to investigate the role and mechanism of tubiquitin-conjugating enzyme E2 C (UBE2C) in acute myeloid leukemia (AML). Initially, UBE2C expression in leukemia was analyzed using the Cancer Genome Atlas database. Further, we silenced UBE2C expression using small-hairpin RNA (sh-RNA). UBE2C expression was detected via the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis. Apoptotic events and reactive oxygen species (ROS) levels were detected by flow cytometry...

Acute myeloid leukemia (AML) remains a therapeutic challenge despite recent therapeutic advances. Although monoclonal antibodies (mAbs) engaging natural killer (NK) cells via antibody-dependent cellular cytotoxicity (ADCC) hold promise in cancer therapy, almost none have received clinical approval for AML, so far. Recently, CD276 (B7-H3) has emerged as a promising target for AML immunotherapy, due to its high expression on leukemic blasts of AML patients. Here, we present the preclinical development of the Fc-optimized CD276 mAb 8H8_SDIE with enhanced CD16 affinity...

A model construction of systemic acute leukemia is challenging. Herein, we established a systemic leukemia mouse model using highly immunodeficient NPG mice without any immunosuppressive treatments. NPG mice received tail intravenous injection of SHI-1 cells at the concentration of 1×107 cells (group A) or 5×107 cells (group B) and randomly sacrificed each seven days post-inoculation. Tumor development was monitored using nested-PCR, peripheral blood-smear analysis, flow cytometry, pathological examinations, and immunohistochemistry...

Myeloperoxidase (MPO) is the most specific marker of the myeloid lineage, essential for diagnosing acute myeloid leukemia and mixed phenotype acute leukemia with myeloid components. In this regard, we present a unique case of B-acute lymphoblastic leukemia (B-ALL) with isolated MPO expression in bone marrow blasts detected by flow cytometry and immunohistochemistry, while peripheral blood blasts were negative for MPO expression. In this report, our discussion encompasses diagnostic pitfalls from a laboratory testing perspective in similar cases and includes a literature review...

BACKGROUND: Myelodysplastic neoplasms (MDS) are myeloid neoplasms characterized by disordered differentiation of hematopoietic stem cells and a predisposition to acute myeloid leukemia (AML). The underline pathogenesis remains unclear. METHODS: In this study, the trajectory of differentiation and mechanisms of leukemic transformation were explored through bioinformatics analysis of single-cell RNA-Seq data from hematopoietic stem and progenitor cells (HSPCs) in MDS patients...

BACKGROUND: Vitamin D deficiency is prevalent among the Indonesian population, particularly in individuals diagnosed with leukemia-lymphoma. The regulation of vitamin D metabolism is influenced by the expression of several enzymes, such as CYP2R1, CYP24A1, and the vitamin D receptor (VDR). This study aimed to scrutinize the gene expression profiles in both mRNA and protein levels of VDR, CYP2R1, and CYP24A1 in leukemia and lymphoma patients. METHOD: The research was a cross-sectional study conducted at Cipto Mangunkusumo Hospital (RSCM) in Jakarta, Indonesia...

Granulopoiesis is a highly ordered and precisely regulated process in which hematopoietic-related transcription factors play crucial roles. These transcription factors form complex regulatory networks through interactions with their co-factors or with each other, and anomalies in these networks can lead to the onset of leukemia. While the structures and functions of dozens of transcription factors involved in this process have been extensively studied, research on the regulatory relationships between these factors remains relatively limited...

Mutant isocitrate dehydrogenases (IDHs) produce R-2-hydroxyglutarate (R-2HG), which inhibits the growth of most acute myeloid leukemia (AML) cells. Here, we showed that necroptosis, a form of programmed cell death, contributed to the antileukemia activity of R-2HG. Mechanistically, R-2HG competitively inhibited the activity of lysine demethylase 2B (KDM2B), an α-ketoglutarate-dependent dioxygenase. KDM2B inhibition increased histone 3 lysine 4 trimethylation levels and promoted the expression of receptor-interacting protein kinase 1 (RIPK1), which consequently caused necroptosis in AML cells...

De novo acute myeloid leukemia (AML) patients with FMS-like tyrosine kinase 3 internal tandem duplications (FLT3-ITD) have worse treatment outcomes. Arsenic trioxide (ATO) used in the treatment of acute promyelocytic leukemia (APL) has been reported to be effective in degrading the FLT3 protein in AML cell lines and sensitizing non-APL AML patient samples in-vitro. We have previously reported that primary cells from FLT3-ITD mutated AML patients were sensitive to ATO in-vitro compared to other non-M3 AML and molecular/pharmacological inhibition of NF-E2 related factor 2 (NRF2), a master regulator of antioxidant response improved the chemosensitivity to ATO and daunorubicin even in non FLT3-ITD mutated cell lines and primary samples...

CD123 "expression" is common in hematological malignancies, including acute lymphoblastic leukemia (ALL). Flotetuzumab is a novel, investigational CD3/CD123 DART®. We conducted a phase 1 study evaluating safety and efficacy of flotetuzumab in relapsed/refractory ALL (Cohort A) and other advanced CD123-positive hematological malignancies (excluding myeloid malignancies) (cohort B). Thirteen patients (9 in Cohort A and 4 in Cohort B) were treated at dose level 1 (500 ng/kg/day) before early closure due to discontinuation of drug development by sponsor...