8,362 results match your criteria: "Erythroleukemia"

Engineering genetic devices for in vivo control of therapeutic T cell activity triggered by the dietary molecule resveratrol.

Proc Natl Acad Sci U S A

August 2021

Synthetic Biology and Biomedical Engineering Laboratory, Biomedical Synthetic Biology Research Center, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China;

Chimeric antigen receptor (CAR)-engineered T cell therapies have been recognized as powerful strategies in cancer immunotherapy; however, the clinical application of CAR-T is currently constrained by severe adverse effects in patients, caused by excessive cytotoxic activity and poor T cell control. Herein, we harnessed a dietary molecule resveratrol (RES)-responsive transactivator and a transrepressor to develop a repressible transgene expression (RES) device and an inducible transgene expression (RES) device, respectively. After optimization, these tools enabled the control of CAR expression and CAR-mediated antitumor function in engineered human cells.

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Multifunctional protein 4.1R regulates the asymmetric segregation of Numb during terminal erythroid maturation.

J Biol Chem

September 2021

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; Department of Pediatrics and Genetics, Harvard Medical School, Boston, Massachusetts, USA; Leukemia Program, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts, USA.

The asymmetric cell division of stem or progenitor cells generates daughter cells with distinct fates that balance proliferation and differentiation. Asymmetric segregation of Notch signaling regulatory protein Numb plays a crucial role in cell diversification. However, the molecular mechanism remains unclear.

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Expression Silencing of Glutathione Peroxidase 4 in Mouse Erythroleukemia Cells Delays In Vitro Erythropoiesis.

Int J Mol Sci

July 2021

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Biochemistry, Charitéplatz 1, 10117 Berlin, Germany.

Among the eight human glutathione peroxidase isoforms, glutathione peroxidase 4 (GPX4) is the only enzyme capable of reducing complex lipid peroxides to the corresponding alcohols. In mice, corruption of the gene leads to embryonic lethality and more detailed expression silencing studies have implicated the enzyme in several physiological processes (e.g.

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In recent years, there has been considerable interest in lectins from marine invertebrates. In this study, the biological activities of a lectin protein isolated from the eggs of Sea hare () were evaluated. The 40 kDa egg lectin (or AKL-40) binds to D-galacturonic acid and D-galactose sugars similar to previously purified isotypes with various molecular weights (32/30 and 16 kDa).

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PTD-mediated delivery of α-globin chain into Κ-562 erythroleukemia cells and α-thalassemic (HBH) patients' RBCs ex vivo in the frame of Protein Replacement Therapy.

J Biol Res (Thessalon)

July 2021

Laboratory of Pharmacology, Department of Pharmacognosy - Pharmacology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124, Thessaloniki, Macedonia, Greece.

Background: α-Thalassemia, a congenital hemoglobinopathy, is characterized by deficiency and/or reduced levels of α-globin chains in serious forms of α-thalassemia (HbH disease/Hb Bart's). This research work deals with a Protein Replacement Therapy approach in order to manage α-thalassemia manifestations, caused by the excess of β-globin chain into HbH RBCs. The main goal was to produce the recombinant human α-globin chain in fusion with TAT, a Protein Transduction Domain, to ex vivo deliver it into HbH patients RBCs, to replace the endogenous missing α-globin chain.

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The ubiquitous mitochondrial protein unfoldase CLPX regulates erythroid heme synthesis by control of iron utilization and heme synthesis enzyme activation and turnover.

J Biol Chem

August 2021

Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Pittsburgh Heart, Lung and Blood Vascular Medicine Institute and Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address:

Heme plays a critical role in catalyzing life-essential redox reactions in all cells, and its synthesis must be tightly balanced with cellular requirements. Heme synthesis in eukaryotes is tightly regulated by the mitochondrial AAA+ unfoldase CLPX (caseinolytic mitochondrial matrix peptidase chaperone subunit X), which promotes heme synthesis by activation of δ-aminolevulinate synthase (ALAS/Hem1) in yeast and regulates turnover of ALAS1 in human cells. However, the specific mechanisms by which CLPX regulates heme synthesis are unclear.

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Optimized cytotoxicity assay for co-suspended effector and target cells.

J Immunol Methods

October 2021

Shanghai Cell Therapy Group Co., LTD, Shanghai 201805, China. Electronic address:

In recent years, adoptive cell therapy of immune effector cells, such as chimeric antigen receptor-T (CAR-T) cells, natural killer (NK) cells, and epitope-specific cytotoxic T lymphocyte (CTL) cells have been employed in clinical trials. In addition, CD19 CAR-T cells have been approved by the FDA for treatment of non-Hodgkin lymphoma and diffuse large B-cell lymphoma. In this context, it is vital to detect cellular cytotoxicity and monitor the quality of ex vivo expanded immune cells before product release and patient infusion.

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DOT1L complex regulates transcriptional initiation in human erythroleukemic cells.

Proc Natl Acad Sci U S A

July 2021

Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China;

DOT1L, the only H3K79 methyltransferase in human cells and a homolog of the yeast Dot1, normally forms a complex with AF10, AF17, and ENL or AF9, is dysregulated in most cases of mixed-lineage leukemia (MLLr), and has been believed to regulate transcriptional elongation on the basis of its colocalization with RNA polymerase II (Pol II), the sharing of subunits (AF9 and ENL) between the DOT1L and super elongation complexes, and the distribution of H3K79 methylation on both promoters and transcribed regions of active genes. Here we show that DOT1L depletion in erythroleukemic cells reduces its global occupancy without affecting the traveling ratio or the elongation rate (assessed by 4sUDRB-seq) of Pol II, suggesting that DOT1L does not play a major role in elongation in these cells. In contrast, analyses of transcription initiation factor binding reveal that DOT1L and ENL depletions each result in reduced TATA binding protein (TBP) occupancies on thousands of genes.

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3,3',5-Triiodothyroacetic acid (TRIAC) induces embryonic ζ-globin expression via thyroid hormone receptor α.

J Hematol Oncol

June 2021

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The human ζ-globin gene (HBZ) is transcribed in primitive erythroid cells only during the embryonic stages of development. Reactivation of this embryonic globin synthesis would likely alleviate symptoms both in α-thalassemia and sickle-cell disease. However, the molecular mechanisms controlling ζ-globin expression have remained largely undefined.

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Studies on the role of alpha 7 nicotinic acetylcholine receptors in K562 cell proliferation and signaling.

Mol Biol Rep

June 2021

Department of Biophysics, School of Medicine, Marmara University, Başıbüyük Health Campus, Basic Medical Sciences Building, Maltepe, 34854, Istanbul, Turkey.

The results we obtained from this study gave information about the determination of alpha 7 nicotinic acetylcholine receptor (α7-nACh) expression in human erythroleukemia cells, as well as whether it has a role in calcium release and cell proliferation in the presence of nicotinic agonist, antagonists. Determining the roles of α7 nicotinic receptors in erythroleukemia cells will also contribute to leukemia-related signal transduction studies. This study is primarily to determine the role of nicotinic agonists and antagonists in cell proliferation, α7 nicotinic acetylcholine receptor expression, and calcium release.

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Cabozantinib is a potent tyrosine kinase inhibitor with multiple targets including MET, VEGFR2, RET, KIT, and FLT3. Cabozantinib is widely used for the treatment of medullary thyroid cancer and renal cell carcinoma. We recently suggested cabozantinib as a potential therapeutic alternative for acute myeloid leukemia (AML) patients with FLT3-internal tandem duplication (FLT3-ITD).

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ERK activation via A1542/3 limonoids attenuates erythroleukemia through transcriptional stimulation of cholesterol biosynthesis genes.

BMC Cancer

June 2021

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Province Science City, High Tech Zone, Baiyun District, Guiyang, 550014, Guizhou Province, People's Republic of China.

Background: Cholesterol plays vital roles in human physiology; abnormal levels have deleterious pathological consequences. In cancer, elevated or reduced expression of cholesterol biosynthesis is associated with good or poor prognosis, but the underlying mechanisms are largely unknown. The limonoid compounds A1542 and A1543 stimulate ERK/MAPK by direct binding, leading to leukemic cell death and suppression of leukemia in mouse models.

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Overcoming the UCB HSCs -Derived NK cells Dysfunction through Harnessing RAS/MAPK, IGF-1R and TGF-β Signaling Pathways.

Cancer Cell Int

June 2021

Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.

Background: The natural killer (NK) cells differentiated from umbilical cord blood (UCB) hematopoietic stem cells (HSCs) may be more suitable for cell-based immunotherapy compared to the NK cells from adult donors. This is due to the possibility to choose alloreactive donors and potentially more robust in vivo expansion. However, the cytotoxicity of UCB-HSC-derived NK cells against cancer cells might be suboptimal.

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In this study, two strains of the yeast were constructed, one of which produced authentic recombinant human granulocyte-macrophage colony-stimulating factor (ryGM-CSF), and the other was a chimera consisting of ryGM-CSF genetically fused with mature human apolipoprotein A-I (ApoA-I) (ryGM-CSF-ApoA-I). Both forms of the cytokine were secreted into the culture medium. The proteins' yield during cultivation in flasks was 100 and 60 mg/L for ryGM-CSF and ryGM-CSF-ApoA-I, respectively.

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Soluble Prokaryotic Overexpression and Purification of Human GM-CSF Using the Protein Disulfide Isomerase b'a' Domain.

Int J Mol Sci

May 2021

Department of Physiology, Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of the colony-stimulating factor (CSF) family, which functions to enhance the proliferation and differentiation of hematopoietic stem cells and other hematopoietic lineages such as neutrophils, dendritic cells, or macrophages. These proteins have thus generated considerable interest in clinical therapy research. A current obstacle to the prokaryotic production of human GM-CSF (hGM-CSF) is its low solubility when overexpressed and subsequent complex refolding processes.

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The Janus kinase (JAK) and epidermal growth factor receptor (EGFR) have been considered as potential targets for cancer therapy due to their role in regulating proliferation and survival of cancer cells. In the present study, the aromatic alkyl-amino analogs of thiazole-based chalcone were selected to experimentally and theoretically investigate their inhibitory activity against JAK2 and EGFR proteins as well as their anti-cancer effects on human cancer cell lines expressing JAK2 (TF1 and HEL) and EGFR (A549 and A431). cytotoxicity screening results demonstrated that the HEL erythroleukemia cell line was susceptible to compounds and , whereas the A431 lung cancer cell line was vulnerable to compound .

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Acyclovir induces fetal hemoglobin via downregulation of γ-globin repressors, BCL11A and SOX6 trans-acting factors.

Biochem Pharmacol

August 2021

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address:

Pharmacological reactivation of developmentally silenced fetal hemoglobin (HbF) is an attractive approach to ameliorate the clinical manifestations of β-thalassemia and sickle cell anemia. Hydroxyurea, the only HbF inducer, has obtained regulatory approval. However, hydroxyurea non-responders and associated myelosuppression making its widespread use undesirable.

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Relation between ABCB1 overexpression and COX2 and ALOX5 genes in human erythroleukemia cell lines.

Prostaglandins Other Lipid Mediat

August 2021

Laboratório de Cultura Celular, ICB, FURG, RS, Brazil; Programa de Pós-Graduação em Ciências Fisiológicas, ICB, FURG, RS, Brazil. Electronic address:

This study aimed to characterize the relationship between the COX2 and ALOX5 genes, as well as their link with the multidrug resistance (MDR) phenotype in sensitive (K562) and MDR (K562-Lucena and FEPS) erythroleukemia cells. For this, the inhibitors of 5-LOX (zileuton) and COX-2 (acetylsalicylic acid-ASA) and cells with the silenced ABCB1 gene were used. The treatment with ASA caused an increase in the gene expression of COX2 and ABCB1 in both MDR cell lines, and a decrease in the expression of ALOX5 in the FEPS cells.

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Acute myeloid leukemia (AML) is a heterogenous malignancy characterized by distinct lineage subtypes and various genetic/epigenetic alterations. As with other neoplasms, AML cells have well-known aerobic glycolysis, but metabolic variations depending on cellular lineages also exist. Lysine-specific demethylase-1 (LSD1) has been reported to be crucial for human leukemogenesis, which is currently one of the emerging therapeutic targets.

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Molecular Landscapes and Models of Acute Erythroleukemia.

Hemasphere

May 2021

University Children's Hospital beider Basel (UKBB), Department of Biomedicine, University of Basel, Basel, Switzerland.

Malignancies of the erythroid lineage are rare but aggressive diseases. Notably, the first insights into their biology emerged over half a century ago from avian and murine tumor viruses-induced erythroleukemia models providing the rationale for several transgenic mouse models that unraveled the transforming potential of signaling effectors and transcription factors in the erythroid lineage. More recently, genetic roadmaps have fueled efforts to establish models that are based on the epigenomic lesions observed in patients with erythroid malignancies.

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Erythroleukemia: an Update.

Curr Oncol Rep

April 2021

Department of Pathology, University of Chicago, Chicago, IL, USA.

Purpose Of The Review: Acute erythroleukemia (AEL) is a rare form of acute myeloid leukemia recognized by erythroblastic proliferation. Many controversies remain around diagnosis influencing prognostic and therapeutic implications relating to this unique leukemia subset.

Recent Findings: The 2016 WHO classification includes more clear and restrictive diagnostic criteria for AEL.

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Pure erythroid leukemia subsequent to acute myelomonocytic leukemia: A case report.

Medicine (Baltimore)

April 2021

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Hematology of Nanjing Medical University.

Rationale: Pure erythroid leukemia is a rare subcategory of acute myeloid leukemia characterized by predominant immature erythroid population. Its occurrence subsequent to acute myelomonocytic leukemia has not been reported before. We reported this rare case to call attention because it may pose a diagnostic challenge.

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The aim of the present study was to investigate the synergistic effect of LY294002 (a PI3K inhibitor) and ABT199 (a BCL2 inhibitor) on the cell cycle in acute myeloid leukemia (AML). The optimal concentration and duration of combined LY294002 and ABT199 were determined in human erythroleukemia (K562), promyelocytic leukemia (HL60) and myeloid leukemia (KG1a) cell lines. The mRNA and protein expression levels of cell cycle‑related molecules, including S‑phase kinase‑associated protein 2 (Skp2), p27, BCL2, Bax, cleaved caspase 3 (caspase‑3) and caspase 9 (caspase‑9) were detected via reverse transcription‑quantitative PCR and western blot analysis, respectively.

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