Prasoon Agarwal

National Bioinformatics Infrastructure of Sweden

Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.

ABSTRACT CGGBP1 (CGG triplet repeat-binding protein 1) regulates cell proliferation, stress response, cytokinesis, telomeric integrity and transcription. It could affect these processes by modulating target gene expression under different conditions. Identification of CGGBP1-target genes and their regulation could reveal how a transcription regulat...

Background CGGBP1 is a repetitive DNA-binding transcription regulator with target sites at CpG-rich sequences such as CGG repeats and Alu-SINEs and L1-LINEs. The role of CGGBP1 as a possible mediator of CpG methylation however remains unknown. At CpG-rich sequences cytosine methylation is a major mechanism of transcriptional repression. Concordantl...

Multiple myeloma (MM) is a malignancy of the antibody-producing plasma cells. MM is a highly heterogeneous disease, which has hampered the identification of a common underlying mechanism for disease establishment as well as the development of targeted therapy. Here we present the first genome-wide profiling of histone H3 lysine 27 and lysine 4 trim...

The antibacterial activity of silver nanoparticles has been well-researched throughout the years, and massive data has been generated describing a specific nanoparticle sample and its antibacterial activity by performing laboratory experiments; however, none have utilized this data to create a means of predicting the antibacterial activity. In this...

Citation: Agarwal, P.; Glowacka, A.; Mahmoud, L.; Bazzar, W.; Larsson, L.-G.; Alzrigat, M. MYCN Amplification Associated with Reduced Expression of Genes Encoding γ-Secretase Complex and NOTCH Signaling Components in Neuroblastoma. Int. J. Mol. Sci. 2023, 24, 8141. https://doi.org/10.3390/ ijms24098141 Academic Editors: Raffaele Addeo and Fabio Mor...

Objective Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the metabolic alterations in adolescents with T2D. Methods We performed a cross sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells with serum metabolomic data from First Nation adolescen...

Background Accumulating evidence links disruptions in phospholipid homeostasis to obesity, type 2 diabetes, and fatty liver diseases. Mice with a heterozygous ablation of the phosphatidylethanolamine (PE) synthesizing enzyme Pcyt2+/− show reduced PE synthesis and turnover and develop an age-dependent metabolic syndrome that is characterized by impa...

Glioblastoma multiforme (GBM) cancer stem cells (GSCs) are one of the strongest contributing factors to treatment resistance in GBM. Identification of biomarkers capable of directly affecting these cells within the bulk tumor is a major challenge associated with the development of new targeting strategies. In this study, we focus on understanding t...

Background: High doses of doxorubicin put cancer patients at risk for developing dilated cardiomyopathy. Previously, we showed that doxorubicin treatment decreases SIRT3 (sirtuin 3), the main mitochondrial deacetylase and increases protein acetylation in rat cardiomyocytes. Here, we hypothesize that SIRT3 expression can attenuate doxorubicin induc...

Aberrant insulin-like growth factor 1 (IGF-1) signaling has been proposed as a contributing factor to the development of neurodegenerative disorders including diabetic neuropathy, and delivery of exogenous IGF-1 has been explored as a treatment for Alzheimer’s disease and amyotrophic lateral sclerosis. However, the role of autocrine/paracrine IGF-1...

It is imperative to identify the mechanisms that confer stemness to the cancer cells for more effective targeting. Moreover, there are not many studies on the link between stemness characteristics and the immune response in tumours. Therefore, in the current study involving GBM, we started with the study of BIRC5 (one of the rare genes differential...

Colon adenocarcinoma (COAD) is a common tumor of the gastrointestinal tract with a high mortality rate. Current research has identified many genes associated with immune infiltration that play a vital role in the development of COAD. In this study, we analysed the prognostic and diagnostic features of such immune-related genes in the context of col...

Through unknown mechanisms, fetal exposure to gestational diabetes mellitus (GDM) increases the risk for cardiovascular disease development later in life. We hypothesize that fetal exposure to GDM alters offspring cardiomyocyte metabolism and left ventricular (LV) function with age. To induce GDM, female rats were fed a high fat (45% kcal) and sucr...

Doxorubicin (DOX) is a chemotherapeutic with dose-dependent cardiotoxic effects that limits its use in patients. Previously we showed that DOX decreases expression of the mitochondrial lysine deacetylase SIRT3 in the mouse heart. We hypothesize that DOX impairs cardiac function and energy production through reduced SIRT3 and altered mitochondrial a...

Tafazzin (TAZ) is a cardiolipin (CL) biosynthetic enzyme important for maintaining mitochondrial function. TAZ impacts both the species and content of CL in the inner mitochondrial membrane which are essential for normal cellular respiration. In pancreatic β-cells, mitochondrial function is closely associated with insulin secretion. However, the ro...

Objective Tafazzin (TAZ) is a cardiolipin (CL) biosynthetic enzyme important for maintaining mitochondrial function. TAZ impacts both the species and content of CL in the inner mitochondrial membrane which are essential for normal cellular respiration. In pancreatic β-cells, mitochondrial function is closely associated with insulin secretion. Howev...

Survivin is one of the rare proteins that is differentially expressed in normal and cancer cells and is directly or indirectly involved in numerous pathways required for tumor maintenance. It is expressed in almost all cancers and its expression has been detected at early stages of cancer. These traits make survivin an exceptionally attractive targ...

Through unknown mechanisms, fetal exposure to gestational diabetes mellitus (GDM) increases the risk for cardiovascular disease development later in life. We hypothesize that fetal exposure to GDM induces alterations in cardiomyocyte metabolism and induces left ventricular (LV) dysfunction with age. GDM was induced in female rats with a high fat (4...

Objective Doxorubicin (DOX) is an effective chemotherapeutic but has dose‐dependent cardiotoxic effects that limits its use in pediatric patients. Previous studies in our lab showed that DOX decreases expression of the mitochondrial lysine deacetylase SIRT3 and mitochondrial phospholipid cardiolipin (CL) in the mouse heart. We hypothesize that DOX...

Cerebral choline metabolism is crucial for normal brain function, and its homoeostasis depends on carrier-mediated transport. Here, we report on four individuals from three families with neurodegenerative disease and homozygous frameshift mutations (Asp517Metfs*19, Ser126Metfs*8, and Lys90Metfs*18) in the SLC44A1 gene encoding choline transporter-l...

Aims/hypotheses: This study aimed to determine the degree of left ventricular (LV) dysfunction and its determinants in adolescents with type 2 diabetes (T2D). We hypothesized that adolescents with T2D would display impaired LV diastolic function and that these cardiovascular complications would be exacerbated in youth exposed to maternal diabetes...

Cerebral choline metabolism is crucial for normal brain function, and its homoeostasis depends on carrier mediated transport. Here, we report on four individuals from three families with neurodegenerative disease and homozygous frameshift mutations (Asp517Metfs*19, Ser126Metfs*8, and Lys90Metfs*18) in the SLC44A1 gene encoding the choline transport...

Objective: Polymorphisms in human major histocompatibility complex (MHC) are the strongest genetic associations with rheumatoid arthritis (RA). Epigenome-wide methylation studies suggest DNA methylation changes within MHC may contribute to disease susceptibility. In this study, we profiled MHC-specific methylated CpGs in autoantibody-positive RA pa...

Gestational diabetes mellitus (GDM) is the most common complication of pregnancy. Children exposed to GDM are at an increased risk of developing cardiometabolic diseases later in life, though the mechanisms responsible are unknown. We hypothesize that fetal exposure to GDM induces alterations in cardiomyocyte metabolism and concomitant left ventric...

Fetal exposure to gestational diabetes mellitus (GDM) and poor postnatal diet are strong risk factors for type 2 diabetes development later in life, but the mechanisms connecting GDM exposure to offspring metabolic health remains unclear. In this study, we aim to determine how GDM interacts with the postnatal diet to affect islet function in the of...

Background Inflammatory bowel disease (IBD) is a collective term for diseases involving inflammation of the gastrointestinal tract, among which Crohn’s disease (CD) and ulcerative colitis (UC) are the two main sub-categories. Although Anti-Saccharomyces cerevisiae antibodies (ASCA) could be a useful biomarker in differentiating CD from ulcerative c...

Objective: Although anti-saccharomyces cerevisiae antibodies (ASCA) could be a useful biomarker in differentiating Crohn's disease (CD) from ulcerative colitis (UC), their role as prognostic markers in children with CD has been under-investigated. This longitudinal prospective observational study aimed to assess the prognostic value of ASCA status...

Barth Syndrome (BTHS) is a rare X-linked genetic disease in which the specific 19 biochemical deficit is a reduction in the mitochondrial phospholipid cardiolipin (CL) as a result of a 20 mutation in the CL transacylase tafazzin. We compared the phosphokinome profile in Epstein-Barr 21 virus transformed lymphoblasts prepared from a BTHS patient wit...

Since 1980, global obesity has doubled, and the incidence of cardiometabolic diseases such as type 2 diabetes and heart disease is also increasing. While genetic susceptibility and adult lifestyle are implicated in these trends, evidence from clinical cohorts, epidemiological studies and animal model experiments support a role for early-life enviro...

Background: Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is primarily expressed in neuronal cells and neuroendocrine cells and has been associated with various diseases, including many cancers. It is a multifunctional protein involved in deubiquitination, ubiquitination and ubiquitin homeostasis, but its specific roles are disputed and still g...

DNA cytosine methylation occurs in all three sequence contexts: CpG and CHG (symmetrically on the two strands) and CHH (asymmetrically on one strand). While mechanisms of CpG methylation regulation are well studied; the non-CpG methylation is beginning to be understood. Cytosine methylation patterns genome-wide are required for gene expression regu...

Genome organisation and gene expression is regulated by specific DNA sequences that include “insulator elements”. Insulator proteins, such as CTCF bind to insulator elements to block spreading of silent chromatin in-cis or inhibit interactions between transcriptional enhancers and promoters. By binding to insulators in a methylation-sensittive mann...

Increasing number of studies have shown nuclear localization of the insulin-like growth factor 1 receptor (nIGF-1R) in tumor cells and its links to adverse clinical outcome in various cancers. Any obvious cell physiological roles of nIGF-1R have, however, still not been disclosed. Previously, we reported that IGF-1R translocates to cell nucleus and...

Multiple Myeloma (MM) is a plasma cell tumor localized to the bone marrow (BM). Despite the fact that current treatment strategies have improved patients' median survival time, MM remains incurable. Epigenetic aberrations are emerging as important players in tumorigenesis making them attractive targets for therapy in cancer including MM. Recently,...

Multiple Myeloma (MM) is a plasma cell tumor localized to the bone marrow (BM). Despite the fact that current treatment strategies have improved patients' median survival time, MM remains incurable. Epigenetic aberrations are emerging as important players in tumorigenesis making them attractive targets for therapy in cancer including MM. Recently,...

Targeted inhibition of components establishing and maintaining epigenetic marks has recently attracted attention as promising novel cancer treatment strategies. Recent reports describing the development of highly selective small inhibitors of EZH2 has brought forward the notion of targeted epigenetic therapy to the polycomb complex. Here we highlig...

Targeted inhibition of components establishing and maintaining epigenetic marks has recently attracted attention as promising novel cancer treatment strategies. Recent reports describing the development of highly selective small inhibitors of EZH2 has brought forward the notion of targeted epigenetic therapy to the polycomb complex. Here we highlig...

Despite the introduction of new treatment options for multiple myeloma (MM), a majority of patients relapse due to the development of resistance. Unraveling new mechanisms underlying resistance could lead to identification of possible targets for combinatorial treatment. Using TRAF3 deleted/mutated MM cell lines, we evaluated the role of the cellul...

Multiple myeloma (MM) is characterized by accumulation of post-germinal center, isotype-switched, long-living plasma cells with retained proliferation capacity within the bone marrow. MM is highly heterogeneous and remains fatal. This heterogeneity has hampered identification of a common underlying mechanism for disease establishment and the develo...

Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) are mature CD51 B-cell malignancies with different biological/clinical characteristics. We recently reported an association between different prognostic subgroups of CLL (i.e., IGHV mutated and unmutated) and genomic methylation pattern. However, the relationship between DNA methylat...

We have previously shown the use of the insulin-like growth factor type 1 receptor tyrosine kinase (IGF-1RTK) inhibitor picropodophyllin (PPP) as an attractive strategy to combat multiple myeloma (MM) in vitro and in vivo. After a combinatorial drug screening, the histone deacetylase inhibitor LBH589 was shown to act in synergy with PPP reducing su...

PURPOSE: We have previously demonstrated the use of the IGF-1RTK inhibitor picropodophyllin (PPP) as an attractive strategy to combat multiple myeloma (MM) in vitro and in vivo. After a combinatorial drug screening the HDAC inhibitor LBH589 was shown to act in synergy with PPP reducing survival of MM cells. In the current study we tried to elucidat...

To understand the molecular pathogenesis of oral submucous fibrosis (OSF), which is a chronic inflammatory disease, gene expression profiling was performed in 10 OSF tissues against 8 pooled normal tissues using oligonucleotide arrays. Microarray results revealed differential expression of 5,288 genes (P ≤ 0.05 and fold change ≥ 1.5). Among these,...

DZNep and LBH589 reduce growth of the RPMI 8226 and U-266-1982 cells. (A) and (B): RPMI 8226 and U-266-1984 were treated with the indicated concentrations of DZNep (48 hours) and LBH589 (24 hours) followed by AlamarBlue assay. At least 2 experiments were performed in triplicates; data are presented as mean percentage of control ±SD. (0.08 MB TIF)

DZNep and LBH589 have mild effect on growth of the normal SK 1064 cells and PBMC. (A) and (B): SK 1064 and PBMC were treated with the indicated concentrations of DZNep (48 hours) and LBH589 (48 hours) followed by resazurin assay. Experiment was performed in triplicates; data are presented as mean percentage of control ±SD. Peripheral blood mononucl...

DZNep and LBH589 deplete EZH2 protein expression in a concentration-dependent manner. (A): The RPMI 8226 cells and (B): The U-266-1984 cells were treated for 48 hours with 0.5, 2.5 and 10 µM DZNep; (C): the RPMI 8226 cells were treated for 72 hours with 4, 10 and 20 nM LBH589 and (D): the U-266-1984 cells were treated for 24 hours with 4, 20 and 10...

H3K27me3 targets among the 10% most under expressed genes in MM, MGUS and MM stage III, corresponding to figure 1a, 1b and 1c. Complete gene list of H3K27me3 targets (Bracken, Dietrich et al. 2006) among the 10% most under expressed genes in MM (Zhan, Hardin et al. 2002), MGUS (Zhan, Barlogie et al. 2007) and MM stage III (Agnelli, Fabris et al. 20...

Primers used in real-time qPCR for chromatin immunoprecipitation (ChIP). Primers used in real-time qPCR for chromatin immunoprecipitation (ChIP). (0.03 MB DOC)

The PRC2 components EED, EZH2 and SUZ12 are overexpressed in MM. (A): MM patients (n = 74) compared to plasma cells (n = 37) and tonsillar tissue (n = 37) (Zhan, Hardin et al. 2002). (B): Smoldering Myeloma patients (n = 12) compared to MGUS patients (n = 44) and normal bone marrow (n = 22) (Zhan, Barlogie et al. 2007). (C): MM stage III patients (...

The PRC2 targets CIITA, GATA2, CDH6, CXCL12 and ICSBP/IRF8 are underexpressed in MM. Target genes were defined by Bracken et al. (Bracken, Dietrich et al. 2006) in embryonic fibroblasts and their expression pattern examined using Oncomine. (A): MM patients (n = 74) compared to plasma cells (n = 37) and tonsillar tissue (n = 37) (Zhan, Hardin et al....

The H3K27-tri-methylated CIITA, GATA2, CDH6, CXCL12 and ICSBP/IRF8 are enriched among genes underexpressed in MM. Enrichment profile generated after a gene-set enrichment (GSE) analysis of the five PRC2 target genes (CIITA, GATA2, CDH6, CXCL12 and ICSBP/IRF8) when compared to Mayo clinic dataset (Chng, Kumar et al. 2007) (GSE6477) using software GS...

Multiple myeloma (MM) is a genetically heterogeneous disease, which to date remains fatal. Finding a common mechanism for initiation and progression of MM continues to be challenging. By means of integrative genomics, we identified an underexpressed gene signature in MM patient cells compared to normal counterpart plasma cells. This profile was enr...

Limbal stem cell deficiency is a challenging clinical problem and the current treatment involves replenishing the depleted limbal stem cell (LSC) pool by either limbal tissue transplantation or use of cultivated limbal epithelial cells (LEC). Our experience of cultivating the LEC on denuded human amniotic membrane using a feeder cell free method, l...

Oral submucous fibrosis, a disease of collagen disorder, has been attributed to arecoline present in the saliva of betel quid chewers. However, the molecular basis of the action of arecoline in the pathogenesis of oral submucous fibrosis is poorly understood. The basic aim of our study was to elucidate the mechanism underlying the action of arecoli...

Transglutaminase-2 (TGM-2) stabilizes extracellular matrix (ECM) proteins by cross-linking and has been implicated in several fibrotic disorders. Arecoline present in betel quid has been proposed as one of the causative factors for oral submucous fibrosis (OSMF). Hence, we hypothesize that arecoline may regulate TGM-2 and may have a role in the pat...