Evaluating the effect of acute myeloblastic leukemia-derived exosomes on the human bone marrow mesenchymal stromal cell proliferation.

Background: The progression of leukemia is substantially associated with the interactions of leukemic cells with surrounding cells within the bone marrow microenvironment (BMM), and these interactions were facilitated using exosomes as vital mediators. The current study aimed to examine the proliferative effects of exosomes derived from the HL-60 cell line, a representative of acute myeloblastic leukemia (AML), on the cell cycle progression of human bone marrow mesenchymal stromal cells (hBM-MSCs), a key element of the BMM.

Methods And Results: hBM-MSCs were treated with different concentrations of AML-derived exosomes from the HL-60 cell line.

Identification of Prognostic Genes in Acute Myeloid Leukemia Microenvironment: A Bioinformatic and Experimental Analysis.

Acute myeloid leukemia (AML) is a lethal hematologic malignancy with a variable prognosis that is highly dependent on the bone marrow microenvironment. Consequently, a better understanding of the AML microenvironment is crucial for early diagnosis, risk stratification, and personalized therapy. In recent years, the role of bioinformatics as a powerful tool in clarifying the complexities of cancer has become more prominent.

Investigating the multifaceted cooperation of autophagy, PI3K/AKT signaling pathways, and INPP4B gene in de novo acute myeloid leukemia patients.

Background: Acute myeloid leukemia (AML) has been the most prevalent form of acute leukemia among adults, and it has been associated with poor survival rates over the last four decades. Understanding the processes involved in leukemogenesis, particularly autophagy and signaling pathways, can provide critical insights into their roles in disease development, risk assessment, and potential therapeutic interventions. This study investigated gene expression changes, focusing on MAP1LC3B and BECN1, related to autophagy, as well as PI3KCA and AKT1 in the PI3K-AKT pathway, and INPP4B, which regulates this signaling cascade.

Expression Changes of SIRT1 and FOXO3a Significantly Correlate with Oxidative Stress Resistance Genes in AML Patients.

The increased metabolism in acute myeloid leukemia (AML) malignant cells resulted in the production of high levels of free radicals, called oxidative stress conditions. To avoid this situation, malignant cells produce a considerable amount of antioxidant agents, which will lead to the release of a continuous low level of reactive oxygen species (ROS), causing genomic damage and subsequent clonal evolution. SIRT1 has a key role in driving the adaptation to this condition, mainly through the deacetylation of FOXO3a that affects the expression of oxidative stress resistance target genes such as Catalase and Manganese superoxide dismutase (MnSOD).

An overview of the molecular and clinical significance of the angiopoietin system in leukemia.

The angiogenesis efficacy in solid tumors and hematological malignancies has been identified for more than twenty years. Although the exact role of angiogenesis in leukemia as a common hematological malignancy has not yet been extensively studied, its effect is demonstrated on the initiation and maintenance of a favorable microenvironment for leukemia cell proliferation. The angiopoietin family is a defined molecular mediator for angiogenesis, which contributes to vascular permeability and angiogenesis initiation.

The effect of microvesicles derived from K562 cells on proliferation and apoptosis of human bone marrow mesenchymal stem cells.

Objectives: Microvesicles (MVs) are small membrane-bound particles that act as a vehicle to transfer their contents, such as proteins, RNAs, and miRNAs, to the target cells, making them undergo several changes. Depending on the origin and the target cell, MVs may cause cell survival or apoptosis. This study investigated the effects of MVs released from the leukemic K562 cell line on the human bone marrow mesenchymal stem cells (hBM-MSCs) to evaluate changes in the survival or apoptosis of the cells in an system.

Effect of Acute Myeloid Leukemia-derived Extracellular Vesicles on Bone Marrow Mesenchymal Stromal Cells: Expression of Poor Prognosis Genes.

Objective: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder resulting from a complex interplay between leukemic cells and supporting factors from their microenvironment. In this context, extracellular vesicles (EVs) have been shown to play an essential role in forming a tumor-protective microenvironment. In this study, we examined the influence of AML-derived EVs on cellular and molecular characterization of bone marrow mesenchymal stromal cells (BM-MSCs), particularly alteration in the expression of genes (IL-6, Gas-6, and Galectin-3) relating to relapse and chemoresistance.

Transcription analysis of a histones modifiers panel coupled with critical tumor suppressor genes displayed frequent changes in patients with AML.: mRNA levels of histones modifiers and TSGs in AML.

Epigenetic alterations could cause leukemia through the activation of normally silent loci or silencing of normally active loci. We herein aimed to compare the expression patterns of a histone modifiers panel consisted of SUV39H1, PRDM16, UHRF2, KDM2B, and KDM3C between acute myeloid leukemia(AML) cells and normal cells and to assess the correlation of these genes with the expression of vital tumor suppressor genes, including p16 and p53. Bone marrow or peripheral blood samples of 50 AML patients at diagnosis and also 18 subjects with a normal hematopoietic system as a control group were obtained after informed consent.

Evaluation of Sestrin 2, Adiponectin, AMPK, and mTOR Genes Expression in Acute Myeloid Leukemia Patients.

Background: Effective treatment of acute myeloid leukemia (AML) is still controversial, therefore; a comprehensive understanding regarding the impaired cellular signaling pathways in AML can be useful in designing new therapeutic approaches. Among signaling pathways involved in AML, the mammalian target of rapamycin (mTOR) signaling pathway is of particular importance. While dysregulation of mTOR signaling has been reported in a wide range of patients with AML, but most studies have focused on mTOR downstream targets, and mTOR upstream targets have been overlooked.

Acute promyelocytic leukemia derived extracellular vesicles conserve PML-RARα transcript from storage-inflicted degradation: a stable diagnosis tool in APL patients.

The early death, which is more common in acute promyelocytic leukemia (APL) patients rather than other types of acute myelocytic leukemia (AML) highlights the importance of appropriate diagnostic method for early detection of this disease. The low sensitivity of the conventional methods, low tumor burden in some patients, and the need for bone marrow sampling are some of the diagnostic challenges on the way of proper detection of APL. Given these, we aimed to compare the efficacy of extracellular vesicles (EVs), as a diagnostic tool, with the existing methods.

Investigating the expression pattern of the angiopoietin-Tie system in ALL and its correlation with baseline characteristics.

Background: Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children. Several environmental and genetic factors are known to be involved in its development and progression. The angiopoietin-Tie system is one of the most critical factors in angiogenesis, and its possible role in solid tumors and leukemia has been previously investigated.

Circulatory miR-155 correlation with platelet and neutrophil recovery after autologous hematopoietic stem cell transplantation, a multivariate analysis.

The involvement of microRNAs in the regulation of hematopoietic stem cells paves the way for their use in the management of autologous HSC transplantation (AHSCT). We aimed to evaluate the predictive value of circulatory microRNAs in extracellular vesicles (EVs) and plasma in platelet and neutrophil engraftment. Circulatory miR-125b, mir-126, miR-150, and miR-155 expression was assessed in isolated EVs and plasma in samples collected from AHSCT candidates.

Evaluation of LKB1 and Serine-Glycine Metabolism Pathway Genes (SHMT1 and GLDC) Expression in AML.

LKB1 is a significant tumor suppressor and epigenetic regulator playing a vital role in different types of cancers. SHMT1 and GLDC are two critical genes of the epigenetic pathway influenced by LKB1. As epigenetic is the major cause of AML pathogenesis, this study aimed at investigating LKB1, SHMT1, and GLDC gene expression levels in acute myeloid leukemia patients.

IGF family effects on development, stability, and treatment of hematological malignancies.

Multiple factors, including growth factors, are shown to be culprits of cancer outset and persistence. Among growth factors, insulin-like growth factors (IGFs) family are of more importance in the prognosis of blood malignancies. After binding to their corresponding receptor, IGFs initiate PI3K/AKT signaling pathway and increase the translation of intracellular proteins, such as cell division-related proteins.

The protective effect of oleuropein against radiation-induced cytotoxicity, apoptosis, and genetic damage in cultured human lymphocytes.

Purpose: The aim of this study was to evaluate the effects of oleuropein radiation protection and to find an effective radioprotector.

Materials And Method: Human mononuclear cells were treated with oleuropein at the concentration of 100 μM (optimum concentration), incubated for 24 h, and then exposed to 2 Gy gamma-rays. The anti-radiation effect of oleuropein was assessed by MTT assay, flow cytometry, comet assay, and micronucleus (MN) assay.

CDK Blockade Using AT7519 Suppresses Acute Myeloid Leukemia Cell Survival through the Inhibition of Autophagy and Intensifies the Anti-leukemic Effect of Arsenic Trioxide.

The strong storyline behind the critical role of cyclin-dependent kinase (CDK) inhibitor proteins in natural defense against malignant transformation not only represents a heroic perspective for these proteins, but also provides a bright future for the application of small molecule inhibitors of CDKs in the novel cancer treatment strategies. The results of the present study revealed that the inhibition of CDKs using pan-CDK inhibitor AT7519, as revealed by the induction of G1 cell cycle arrest as well as the reduction of cyclins expression, resulted in decreased survival in acute myeloid leukemia (AML)-derived KG-1 cells, either in the context of single agent or in combination with arsenic trioxide (ATO). Apart from alterations in the expression of proliferation and apoptotic genes, the anti-survival property of AT7519 was coupled with the inhibition of autophagy-related genes.

The Expression of P53, MDM2, c-myc, and P14 Genes in Newly Diagnosed Acute Lymphoblastic Leukemia Patients.

The treatment response of acute lymphoblastic leukemia (ALL) depends on the percentage of lymphoblasts, cytogenetic aberrations, and altered gene expression. The analysis of the gene expression is applicable for determination of risk stratification and prognosis of cancers. c-MYC, P14, MDM2, and P53 play a vital role in cell survival through a functional network.

Evaluation of growth factor independence 1 expression in patients with acute myeloid leukemia.

Objective: Growth factor independence 1 (GFI1), a transcriptional repressor, is required for hematopoietic stem cell maintenance and self-renewal in addition to controlling differentiation and proliferation of myeloid cells. As murine studies have demonstrated that this transcription factor has a notable role in the initiation and progression of acute myeloid leukemia (AML) disease, the aim of the current study was to investigate and review the influence of GFI1 in human AML cells.

Methods: GFI1 expression levels were measured by means of real-time polymerase chain reaction in 96 primary AML samples which were then compared to gene expression levels observed in 18 healthy subjects.

Biodecomposition of Phenanthrene and Pyrene by a Genetically Engineered .

Background: Genetically engineered microorganisms (GEMs) can be used for bioremediation of the biological pollutants into nonhazardous or less-hazardous substances, at lower cost. Polycyclic aromatic hydrocarbons (PAHs) are one of these contaminants that associated with a risk of human cancer development. Genetically engineered E.

Standardization of Plasma Rich in Growth Factors (PRGF) and its effects on androgenic hair loss.

Androgenic alopecia (AGA), as the most common cause of hair loss, is a chronic process that affects 80% of men and 50% of women throughout life. Existing and approved treatments for this condition are limited, and unfortunately, the length of treatment is long, while its efficacy is not much suitable. Plasma rich in growth factors (PRGF) autologous therapy is based on the delivery of a pool of bioactive molecules impressive for the treatment of AGA.

The antioxidant curcumin postpones ovarian aging in young and middle-aged mice.

Reproductive senescence is accompanied by a reduced number and quality of ovarian follicles in response to the accumulation of free radicals and the process of apoptosis. Having selected mice as models, we examined the hypothesis that curcumin as an antioxidant and anti-inflammatory agent might prevent or retard ovarian aging. Female NMRI 21-day-old mice were divided into control, vehicle and curcumin groups.

Evaluation of ATG7 and Light Chain 3 (LC3) Autophagy Genes Expression in AML Patients.

Background And Aim: Autophagy, known as cell death type II, is a housekeeping pathway that currently has been worked on in matters of tumorigenesis and leukomogenesis. Therefore, expression levels of ATG7 and LC3 as two key genes in AML patients are targeted in this study.

Material And Method: This study was performed on 55 de novo AML patients against 17 healthy volunteers, acquired samples from bone marrow (BM) and peripheral blood (PB) sources in different ages and gender.