8,117 results match your criteria Erythroleukemia

Cabozantinib promotes erythroid differentiation in K562 erythroleukemia cells through global changes in gene expression and JNK activation.

Cancer Gene Ther 2021 Jun 11. Epub 2021 Jun 11.

Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.

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). Read More

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

BMC Cancer 2021 Jun 9;21(1):680. Epub 2021 Jun 9.

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. Read More

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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 2021 Jun 7;21(1):298. Epub 2021 Jun 7.

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. Read More

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Construction of Recombinant Human GM-CSF and GM-CSF-ApoA-I Fusion Protein and Evaluation of Their Biological Activity.

Pharmaceuticals (Basel) 2021 May 13;14(5). Epub 2021 May 13.

Institute of Biochemistry of Federal Research Center of Fundamental and Translational Medicine (FRC FTM), Novosibirsk, 2 Timakova Street, Novosibirsk 630117, Russia.

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. Read More

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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 2021 May 17;22(10). Epub 2021 May 17.

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. Read More

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Discovery of novel JAK2 and EGFR inhibitors from a series of thiazole-based chalcone derivatives.

RSC Med Chem 2021 Mar 26;12(3):430-438. Epub 2021 Feb 26.

Structural and Computational Biology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University Bangkok 10330 Thailand +662 2185418 +662 2185426.

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 . Read More

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

Biochem Pharmacol 2021 May 16;190:114612. Epub 2021 May 16.

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. Read More

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

Prostaglandins Other Lipid Mediat 2021 May 8;155:106553. Epub 2021 May 8.

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. Read More

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LSD1 defines erythroleukemia metabolism by controlling the lineage-specific transcription factors GATA1 and C/EBPα.

Blood Adv 2021 05;5(9):2305-2318

Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, and.

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. Read More

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Molecular Landscapes and Models of Acute Erythroleukemia.

Hemasphere 2021 May 21;5(5):e558. Epub 2021 Apr 21.

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. Read More

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Erythroleukemia: an Update.

Curr Oncol Rep 2021 Apr 20;23(6):69. Epub 2021 Apr 20.

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. Read More

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

Medicine (Baltimore) 2021 Apr;100(15):e25528

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. Read More

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Synergistic effects of LY294002 and ABT199 on the cell cycle in K562, HL60 and KG1a cells.

Oncol Rep 2021 Jun 13;45(6). Epub 2021 Apr 13.

Department of Hematology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.

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. Read More

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Increased ERK phosphorylation and caveolin-1 expression on K562 human chronic myelogenous leukemia cells by jacalin, a dietary plant lectin.

Glycoconj J 2021 Jun 9;38(3):361-368. Epub 2021 Apr 9.

School of Life Sciences, B S A Crescent Institute of Science and Technology, Vandalur, Chennai, Tamil Nadu, 600048, India.

The potential antitumor effects of jacalin, the plant lectin that specifically recognizes the tumor-associated Thomsen-Friedenreich antigen has been extensively studied. We had earlier reported jacalin to be mitogenic to K562, the Bcr-Abl expressing erythroleukemia cell line. The dearth of studies highlighting the proliferative effects of jacalin and other lectins motivated us to unveil the mechanism underlying the mitogenic effects of jacalin. Read More

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Stress-induced transcriptional memory accelerates promoter-proximal pause release and decelerates termination over mitotic divisions.

Mol Cell 2021 04 29;81(8):1715-1731.e6. Epub 2021 Mar 29.

Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland. Electronic address:

Heat shock instantly reprograms transcription. Whether gene and enhancer transcription fully recover from stress and whether stress establishes a memory by provoking transcription regulation that persists through mitosis remained unknown. Here, we measured nascent transcription and chromatin accessibility in unconditioned cells and in the daughters of stress-exposed cells. Read More

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Nifuroxazide as JAK2 inhibitor: A binding mode proposal and Hel cell proliferation assay.

Eur J Pharm Sci 2021 Jul 26;162:105822. Epub 2021 Mar 26.

Grupo de Pesquisas Químico-Farmacêuticas, Departamento de Ciências Farmacêuticas, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Campus Diadema. Electronic address:

Nifuroxazide has been employed as an anti-diarrheic agent since 1966, but in the last decade has brought to the research spotlight again due to its recently described antitumoral activity through the JAK2 inhibitory potential. Since 2008, more than 70 papers have been published about the issue and more are expected to the following years. Herein we discuss the findings of molecular modelling studies which were performed to elucidate the potential binding mode of this drug into the JAK2 ATP recognition site and also into the allosteric region near the catalytic site. Read More

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Repurposing of glycine transport inhibitors for the treatment of erythropoietic protoporphyria.

Cell Chem Biol 2021 Mar 13. Epub 2021 Mar 13.

Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland. Electronic address:

Erythropoietic protoporphyria (EPP) is a rare disease in which patients experience severe light sensitivity. It is caused by a deficiency of ferrochelatase (FECH), the last enzyme in heme biosynthesis (HBS). The lack of FECH causes accumulation of its photoreactive substrate protoporphyrin IX (PPIX) in patients' erythrocytes. Read More

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Interplay between FLI-1 and the LDB1 complex in murine erythroleukemia cells and during megakaryopoiesis.

iScience 2021 Mar 20;24(3):102210. Epub 2021 Feb 20.

Department of Cell Biology, Erasmus Medical Centre, 3015CN Rotterdam, the Netherlands.

Transcription factors are key players in a broad range of cellular processes such as cell-fate decision. Understanding how they act to control these processes is of critical importance for therapy purposes. FLI-1 controls several hematopoietic lineage differentiation including megakaryopoiesis and erythropoiesis. Read More

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Different responses of normal cells (red blood cells) and cancer cells (K562 and K562/Dox cells) to low-dose Cs gamma-rays.

Mol Clin Oncol 2021 Apr 23;14(4):74. Epub 2021 Feb 23.

Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.

High-dose radiation is deleterious to cells or tissues. However, the health risks of exposure to low-dose radiation remain unclear. The present study aimed to investigate the biological responses of low-dose gamma-ray exposure to normal red blood cells (RBCs) and erythroleukemia (K562 and K562/Dox) cancer cells. Read More

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To bi or not to bi: Acute erythroid leukemias and hematopoietic lineage choice.

Exp Hematol 2021 May 16;97:6-13. Epub 2021 Feb 16.

MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, UK. Electronic address:

Acute erythroid leukemia (AEL) is an acute leukemia characterized by erythroid lineage transformation. The World Health Organization (WHO) 2008 classification recognized two subtypes of AEL: bilineage erythroleukemia (erythroid/myeloid leukemia) and pure erythroid leukemia. The erythroleukemia subtype was removed in the updated 2016 WHO classification, with about half of cases reclassified as myelodysplastic syndrome (MDS) and half as acute myeloid leukemia (AML). Read More

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Active hematopoiesis triggers exosomal release of PRDX2 that promotes osteoclast formation.

Physiol Rep 2021 Feb;9(3):e14745

Faculty of Dentistry, McGill University, Montréal, QC, Canada.

Hematopoietic disorders, particularly hemolytic anemias, commonly lead to bone loss. We have previously reported that actively proliferating cancer cells stimulate osteoclastogenesis from late precursors in a RANKL-independent manner. We theorized that cancer cells exploit the physiological role of bone resorption to support expanding hematopoietic bone marrow and examined if hematopoietic cells can trigger osteoclastogenesis. Read More

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February 2021

Succinate Accumulation Links Mitochondrial MnSOD Depletion to Aberrant Nuclear DNA Methylation and Altered Cell Fate.

J Exp Pathol (Wilmington) 2020 9;1(2):60-70. Epub 2020 Dec 9.

Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa 52242, USA.

Previous studies showed that human cell line HEK293 lacking mitochondrial superoxide dismutase (MnSOD) exhibited decreased succinate dehydrogenase (SDH) activity, and mice lacking MnSOD displayed significant reductions in SDH and aconitase activities. Since MnSOD has significant effects on SDH activity, and succinate is a key regulator of TET enzymes needed for proper differentiation, we hypothesized that loss would lead to succinate accumulation, inhibition of TET activity, and impaired erythroid precursor differentiation. To test this hypothesis, we genetically disrupted the gene using the CRISPR/Cas9 genetic strategy in a human erythroleukemia cell line (HEL 92. Read More

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December 2020

Whole transcriptome sequencing and integrated network analysis elucidates the effects of 3,8-Di-O-methylellagic acid 2-O-glucoside derived from Sanguisorba offcinalis L., a novel differentiation inducer on erythroleukemia cells.

Pharmacol Res 2021 Apr 12;166:105491. Epub 2021 Feb 12.

School of Pharmacy, Southwest Medical University, Luzhou 646000, China; Education Ministry Key Laboratory of Medical Electrophysiology, Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Southwest Medical University, Luzhou 646000, China. Electronic address:

Acute erythroid leukemia (AEL) is a rare and aggressive hematologic malignancy with no specific treatment. Sanguisorba officinalis L. (S. Read More

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miR-16-5p Promotes Erythroid Maturation of Erythroleukemia Cells by Regulating Ribosome Biogenesis.

Pharmaceuticals (Basel) 2021 Feb 9;14(2). Epub 2021 Feb 9.

Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.

miRNAs constitute a class of non-coding RNA that act as powerful epigenetic regulators in animal and plant cells. In order to identify putative tumor-suppressor miRNAs we profiled the expression of various miRNAs during differentiation of erythroleukemia cells. RNA was purified before and after differentiation induction and subjected to quantitative RT-PCR. Read More

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February 2021

Ubash3b promotes TPA-mediated suppression of leukemogenesis through accelerated downregulation of PKCδ protein.

Biochimie 2021 May 5;184:8-17. Epub 2021 Feb 5.

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, Guizhou, 550014, PR China. Electronic address:

Acquired drug-resistance, often involving downregulation or mutations in the target protein, is a major caveat in precision medicine. Understanding mechanisms of resistance to therapeutic drugs may unravel strategies to overcome or prevent them. We previously identified phorbol ester (PE) compounds such as TPA that induce Protein Kinase δ (PKCδ), thereby suppressing leukemogenesis. Read More

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L20, a Calothrixin B analog, induces intrinsic apoptosis on HEL cells through ROS/γ-H2AX/p38 MAPK pathway.

Biomed Pharmacother 2021 May 5;137:111336. Epub 2021 Feb 5.

State Key Laboratory for Functions and Applications of Medicinal Plants/Department of Immunology, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR China. Electronic address:

Erythroleukemia is a malignant disease in the blood system. Quinones consists of a class of antitumor agents. Calothrixin B is a carbazole-1,4-quinone alkaloid isolated from Calothrix cyanobacteria with a unique indolo[3,2-j] phenanthridine framework. Read More

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Modeling and targeting of erythroleukemia by hematopoietic genome editing.

Blood 2021 Mar;137(12):1628-1640

Department of Pathology, St Jude Children's Research Hospital, Memphis, TN.

Acute erythroid leukemia (AEL) is characterized by a distinct morphology, mutational spectrum, lack of preclinical models, and poor prognosis. Here, using multiplexed genome editing of mouse hematopoietic stem and progenitor cells and transplant assays, we developed preclinical models of AEL and non-erythroid acute leukemia and describe the central role of mutational cooperativity in determining leukemia lineage. Different combination of mutations in Trp53, Bcor, Dnmt3a, Rb1, and Nfix resulted in the development of leukemia with an erythroid phenotype, accompanied by the acquisition of alterations in signaling and transcription factor genes that recapitulate human AEL by cross-species genomic analysis. Read More

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Super-enhancer mediated regulation of adult β-globin gene expression: the role of eRNA and Integrator.

Nucleic Acids Res 2021 02;49(3):1383-1396

Department of Biochemistry and Molecular Biology, Center for Epigenetics, Genetics Institute, UF Health Cancer Center, Powell-Gene Therapy Center, Gainesville, FL 32610, USA.

Super-enhancers (SEs) mediate high transcription levels of target genes. Previous studies have shown that SEs recruit transcription complexes and generate enhancer RNAs (eRNAs). We characterized transcription at the human and murine β-globin locus control region (LCR) SE. Read More

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February 2021

The histone methyltransferase inhibitor A-366 enhances hemoglobin expression in erythroleukemia cells upon co-exposure with chemical inducers in culture.

J Biol Res (Thessalon) 2021 Jan 6;28(1). Epub 2021 Jan 6.

Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.

Background: Erythroleukemia is caused by the uncontrolled multiplication of immature erythroid progenitor cells which fail to differentiate into erythrocytes. By directly targeting this class of malignant cells, the induction of terminal erythroid differentiation represents a vital therapeutic strategy for this disease. Erythroid differentiation involves the execution of a well-orchestrated gene expression program in which epigenetic enzymes play critical roles. Read More

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January 2021

Analyses of putative anti-cancer potential of three STAT3 signaling inhibitory compounds derived from .

Biochem Biophys Rep 2021 Mar 24;25:100882. Epub 2020 Dec 24.

Graduate School of Biostudies, Kyoto University, Kyoto, 606-8502, Japan.

The extract of (Common Sage) exhibited inhibitory activity of STAT3 signal after screening of several plants extracts using the STAT3-responsive reporter system. Cirsiliol, luteolin, and carnosol were identified from the methanol extract of as inhibitors of STAT3 signaling and the effects of these three compounds on STAT3 protein or growth inhibition on cancer cells was compared. Luteolin at the dose of 90 μM clearly suppressed the phosphorylation of STAT3 induced by IL-6, while carnosol was prone to decrease total STAT3 proteins at high doses (>90 μM). Read More

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