8,052 results match your criteria Erythroleukemia


Mutations in the iron-sulfur cluster biogenesis protein HSCB cause congenital sideroblastic anemia.

J Clin Invest 2020 Jul 7. Epub 2020 Jul 7.

Pathology, Boston Children's Hospital, Boston, United States of America.

The congenital sideroblastic anemias (CSAs) can be caused by primary defects in mitochondrial iron-sulfur cluster (Fe-S) biogenesis. HSCB (heat shock cognate B), which encodes a mitochondrial co-chaperone, also known as HSC20 (heat shock cognate protein 20), is the partner of mitochondrial heat shock protein A9 (HSPA9). Together with glutaredoxin 5 (GLRX5), HSCB and HSPA9 facilitate the transfer of nascent two-iron, two-sulfur ([2Fe-2S]) clusters to recipient mitochondrial proteins. Read More

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http://dx.doi.org/10.1172/JCI135479DOI Listing

Low-Density Lipoproteins, High-Density Lipoproteins (HDL), and HDL-Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability.

Lipids 2020 Jun 19. Epub 2020 Jun 19.

Department of Biology, Fairfield University, Fairfield, CT, 06824, USA.

Cellular lipid metabolism, lipoprotein interactions, and liver X receptor (LXR) activation have been implicated in the pathophysiology and treatment of cancer, although findings vary across cancer models and by lipoprotein profiles. In this study, we investigated the effects of human-derived low-density lipoproteins (LDL), high-density lipoproteins (HDL), and HDL-associated proteins apolipoprotein A1 (apoA1) and serum amyloid A (SAA) on markers of viability, cholesterol flux, and differentiation in K562 cells-a bone marrow-derived, stem-like erythroleukemia cell model of chronic myelogenous leukemia (CML). We further evaluated whether lipoprotein-mediated effects were altered by concomitant LXR activation. Read More

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http://dx.doi.org/10.1002/lipd.12254DOI Listing

[Navitoclax Combined with Daunorubicin Promotes Apoptosis of Erythroleukemia Cell Lines K562, HEL and TF-1].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Jun;28(3):724-730

Pediatric Leukemia Diagnosis and Treatment Center, Institute of Hematology and Blood Disease Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China,E-mail:

Objective: To study the effect of apoptotic drug Navitoclax (NTX) combined with chemotherapy drug Daunorubicin (DNR) on apoptosis of erythroleukemia cells.

Methods: K562, HEL and TF-1 cells in logarithmic growth phase were treated with NTX, DNR and combination of the two drugs. CCK-8 test, Annexin V-DAPI double-staining flow cytometry, real-time RT-PCR were used to detect cell growth, cell apoptosis and expression of BAX, BAK, BCL-2, BCL-xl and BIM respectively. Read More

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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2020.03.002DOI Listing

Paris Saponin VII Induces Apoptosis and Cell Cycle Arrest in Erythroleukemia Cells by a Mitochondrial Membrane Signaling Pathway.

Anticancer Agents Med Chem 2020 Jun 15. Epub 2020 Jun 15.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou Province-550014. China.

Background And Purpose: Leukemia considered a top-listed ailment, according to WHO, which contributes to the death of a major population of the world every year. Paris Saponin VII (PS), a saponin which was isolated from the roots of Trillium kamtschaticum, from our group, was reported to provide hemostatic, cytotoxic and antimicrobial activities. However, its molecular mechanism underlying the anti-proliferative effects remains unclear. Read More

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http://dx.doi.org/10.2174/1871520620666200615134039DOI Listing

Nuclear interacting SET domain protein 1 inactivation impairs GATA1-regulated erythroid differentiation and causes erythroleukemia.

Nat Commun 2020 Jun 12;11(1):2807. Epub 2020 Jun 12.

University Children's Hospital Basel, Basel, Switzerland.

The nuclear receptor binding SET domain protein 1 (NSD1) is recurrently mutated in human cancers including acute leukemia. We show that NSD1 knockdown alters erythroid clonogenic growth of human CD34 hematopoietic cells. Ablation of Nsd1 in the hematopoietic system of mice induces a transplantable erythroleukemia. Read More

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http://dx.doi.org/10.1038/s41467-020-16179-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293310PMC

Clostridium perfringens epsilon toxin binds to erythrocyte MAL receptors and triggers phosphatidylserine exposure.

J Cell Mol Med 2020 May 28. Epub 2020 May 28.

Graduate College, Anhui Medical University, Anhui, China.

Epsilon toxin (ETX) is a 33-kDa pore-forming toxin produced by type B and D strains of Clostridium perfringens. We previously found that ETX caused haemolysis of human red blood cells, but not of erythrocytes from other species. The cellular and molecular mechanisms of ETX-mediated haemolysis are not well understood. Read More

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http://dx.doi.org/10.1111/jcmm.15315DOI Listing

Development and characterization of a fully human antibody targeting SCF/c-kit signaling.

Int J Biol Macromol 2020 May 11;159:66-78. Epub 2020 May 11.

College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, 206 World Cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 16499, Republic of Korea; Novelty Nobility, 227 Unjung-ro, Seongnam-si, Gyeonggi-do 13477, Republic of Korea. Electronic address:

CD117/c-kit, a tyrosine kinase receptor, plays a critical role in hematopoiesis, pigmentation, and fertility. The overexpression and activation of c-kit are thought to promote tumor growth and have been reported in various cancers, including leukemia, glioblastoma and mastocytosis. To disrupt the SCF/c-kit signaling axis in cancer, we generated a c-kit antagonist human antibody (NN2101) that binds to domain 2/3 of c-kit. Read More

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http://dx.doi.org/10.1016/j.ijbiomac.2020.05.045DOI Listing

FtH-Mediated ROS Dysregulation Promotes CXCL12/CXCR4 Axis Activation and EMT-Like Trans-Differentiation in Erythroleukemia K562 Cells.

Front Oncol 2020 5;10:698. Epub 2020 May 5.

Department of Experimental and Clinical Medicine, Research Center of Biochemistry and Advanced Molecular Biology, "Magna Græcia" University of Catanzaro, Catanzaro, Italy.

The cell-microenvironment communication is essential for homing of hematopoietic stem cells in stromal niches. Recent evidences support the involvement of epithelial-to-mesenchymal (EMT) process in hematopoietic stem cell homeostasis as well as in leukemia cells invasiveness and migration capability. Here, we demonstrate that the alteration of iron homeostasis and the consequent increase of redox metabolism, mediated by the stable knock down of ferritin heavy chain (FtH), enhances the expression of CXCR4 in K562 erythroleukemia cells, thus promoting CXCL12-mediated motility. Read More

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http://dx.doi.org/10.3389/fonc.2020.00698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214836PMC

Human erythroleukemia genetics and transcriptomes identify master transcription factors as functional disease drivers.

Blood 2020 Apr 29. Epub 2020 Apr 29.

Institut Gustave Roussy, Villejuif, France.

Acute erythroleukemia (AML-M6 or AEL) is a rare but aggressive hematologic malignancy. Previous studies showed that AEL leukemic cells often carry complex karyotypes and mutations in known AML-associated oncogenes. To better define the underlying molecular mechanisms driving the erythroid phenotype, we studied a series of 33 AEL samples representing three genetic AEL subgroups including TP53-mutated, epigenetic regulator-mutated (e. Read More

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http://dx.doi.org/10.1182/blood.2019003062DOI Listing

JAK2 inhibition in JAK2-bearing leukemia cells enriches CD34 leukemic stem cells that are abolished by the telomerase inhibitor GRN163L.

Biochem Biophys Res Commun 2020 Jun 22;527(2):425-431. Epub 2020 Apr 22.

Department of Medicine, Division of Hematology, Center for Molecular Medicine (CMM) and Bioclinicum, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.

The activating-mutation of JAK2V617F drives the development of myeloproliferative neoplasms (MPNs). Several JAK2 inhibitors such as ruxolitinib and gandotinib (LY2784544) currently in clinical trials and, provide improvements in MPNs including myelofibrosis. However, JAK2 inhibitors are non-curative and murine experiments show that JAK2 inhibitors don't eradicate MPN stem cells and it is currently unclear how they escape. Read More

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http://dx.doi.org/10.1016/j.bbrc.2020.04.058DOI Listing

Comprehensive proteomic analysis of murine terminal erythroid differentiation.

Blood Adv 2020 Apr;4(7):1464-1477

INSERM U1016, Centre National Recherche Scientifique (CNRS) UMR8104, Institut Cochin, Université de Paris, Paris, France.

Murine-based cellular models have provided and continue to provide many useful insights into the fundamental mechanisms of erythropoiesis, as well as insights into the pathophysiology of inherited and acquired red cell disorders. Although detailed information on many aspects of these cell models is available, comprehensive proteomic data are lacking. This is a critical knowledge gap, as proteins are effectors of most biologic processes. Read More

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http://dx.doi.org/10.1182/bloodadvances.2020001652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160260PMC

Cellular, transcriptomic and isoform heterogeneity of breast cancer cell line revealed by full-length single-cell RNA sequencing.

Comput Struct Biotechnol J 2020 19;18:676-685. Epub 2020 Mar 19.

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor 48109, MI, United States.

Tumor heterogeneity is generated through a combination of genetic and epigenetic mechanisms, the latter of which plays an important role in the generation of stem like cells responsible for tumor formation and metastasis. Although the development of single cell transcriptomic technologies holds promise to deconvolute this complexity, a number of these techniques have limitations including drop-out and uneven coverage, which challenge the further delineation of tumor heterogeneity. We adopted deep and full-length single-cell RNA sequencing on Fluidigm's Polaris platform to reveal the cellular, transcriptomic, and isoform heterogeneity of SUM149, a triple negative breast cancer (TNBC) cell line. Read More

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http://dx.doi.org/10.1016/j.csbj.2020.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114460PMC

Identification of a selective inhibitor of IDH2/R140Q enzyme that induces cellular differentiation in leukemia cells.

Cell Commun Signal 2020 Apr 3;18(1):55. Epub 2020 Apr 3.

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100#, Shizi Street, Hongshan Road, Nanjing, 210028, Jiangsu, China.

Background: IDH2/R140Q mutation is frequently detected in acute myeloid leukemia (AML). It contributes to leukemia via accumulation of oncometabolite D-2-HG. Therefore, mutant IDH2 is a promising target for AML. Read More

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http://dx.doi.org/10.1186/s12964-020-00536-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126369PMC

Gains of EPOR and ERG genes in adult erythroleukaemia.

Br J Haematol 2020 May 29;189(4):e174-e177. Epub 2020 Mar 29.

Laboratoire d'Oncologie Prédictive, Centre de Recherche en Cancérologie de Marseille (CRCM), UMR 1068 Inserm, CNRS UMR7258, Institut Paoli-Calmettes, Aix-Marseille Université UM105, Marseille, France.

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http://dx.doi.org/10.1111/bjh.16586DOI Listing

K562 erythroleukemia line as a possible reticulocyte source to culture Plasmodium vivax and its surrogates.

Exp Hematol 2020 02 30;82:8-23. Epub 2020 Jan 30.

Biomedical Primate Research Centre, Rijswijk, The Netherlands. Electronic address:

Establishing an in vitro "red blood cell matrix" that would allow uninterrupted access to a stable, homogeneous reticulocyte population would facilitate the establishment of continuous, long-term in vitro Plasmodium vivax blood stage cultures. In this study, we have explored the suitability of the erythroleukemia K562 cell line as a continuous source of such reticulocytes and have investigated regulatory factors behind the terminal differentiation (and enucleation, in particular) of this cell line that can be used to drive the reticulocyte production process. The Duffy blood group antigen receptor (Fy), essential for P. Read More

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http://dx.doi.org/10.1016/j.exphem.2020.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097847PMC
February 2020

TSPO2 translocates 5-aminolevulinic acid into human erythroleukemia cells.

Biol Cell 2020 Apr 5;112(4):113-126. Epub 2020 Feb 5.

Sorbonne Université, Ecole Normale Supérieure, PSL University, CNRS, Laboratoire des Biomolécules (LBM), F-75005, Paris, France.

Background: 5-Aminolevulinic acid (ALA) is the first precursor of heme biosynthesis pathway. The exogenous addition of ALA to cells leads to protoporphyrin IX (PPIX) accumulation that has been exploited in photodynamic diagnostic and photodynamic therapy. Several types of ALA transporters have been described depending on the cell type, but there was no clear entry pathway for erythroid cells. Read More

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http://dx.doi.org/10.1111/boc.201900098DOI Listing

OT-82, a novel anticancer drug candidate that targets the strong dependence of hematological malignancies on NAD biosynthesis.

Leukemia 2020 Jul 2;34(7):1828-1839. Epub 2020 Jan 2.

Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

Effective treatment of some types of cancer can be achieved by modulating cell lineage-specific rather than tumor-specific targets. We conducted a systematic search for novel agents selectively toxic to cells of hematopoietic origin. Chemical library screenings followed by hit-to-lead optimization identified OT-82, a small molecule with strong efficacy against hematopoietic malignancies including acute myeloblastic and lymphoblastic adult and pediatric leukemias, erythroleukemia, multiple myeloma, and Burkitt's lymphoma in vitro and in mouse xenograft models. Read More

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http://dx.doi.org/10.1038/s41375-019-0692-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326709PMC

The PAX-SIX-EYA-DACH network modulates GATA-FOG function in fly hematopoiesis and human erythropoiesis.

Development 2020 01 3;147(1). Epub 2020 Jan 3.

Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA

The GATA and PAX-SIX-EYA-DACH transcriptional networks (PSEDNs) are essential for proper development across taxa. Here, we demonstrate novel PSEDN roles in hematopoiesis and in human erythropoiesis Using genetics, we show that PSEDN members function with GATA to block lamellocyte differentiation and maintain the prohemocyte pool. Overexpression of human SIX1 stimulated erythroid differentiation of human erythroleukemia TF1 cells and primary hematopoietic stem-progenitor cells. Read More

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http://dx.doi.org/10.1242/dev.177022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983716PMC
January 2020

Chemical Composition and in Vitro Cytotoxic Screening of Sixteen Commercial Essential Oils on Five Cancer Cell Lines.

Chem Biodivers 2020 Jan 12;17(1):e1900478. Epub 2019 Dec 12.

Department of Biology, University of Malta, Msida MSD, 2080, Malte.

The in vitro cytotoxic activity on human cancer cell lines of sixteen commercial EOs such as Aloysia citriodora, Boswellia sacra, Boswellia serrata, Cinnamomum zeylanicum, Cistus ladanifer, Citrus × aurantium, Citrus limon, Citrus sinensis, Cymbopogon citratus, Foeniculum vulgare, Illicium verum, Litsea cubeba, Satureja montana, Syzygium aromaticum, Thymus capitatus and Thymus vulgaris was performed using the MTT reduction assay. The screening was carried out on human cancer cells of breast adenocarcinoma (MCF7, T47D and MDA-MB-231), chronic myelogenous erythroleukemia (K562) and neuroblastoma cell lines (SH-SY5Y). C. Read More

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http://dx.doi.org/10.1002/cbdv.201900478DOI Listing
January 2020

Development of a MEL Cell-Derived Allograft Mouse Model for Cancer Research.

Cancers (Basel) 2019 Nov 1;11(11). Epub 2019 Nov 1.

Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Korea.

Murine erythroleukemia (MEL) cells are often employed as a model to dissect mechanisms of erythropoiesis and erythroleukemia in vitro. Here, an allograft model using MEL cells resulting in splenomegaly was established to develop a diagnostic model for isolation/quantification of metastatic cells, anti-cancer drug screening, and evaluation of the tumorigenic or metastatic potentials of molecules in vivo. In this animal model, circulating MEL cells from the blood stream were successfully isolated and quantified with an additional in vitro cultivation step. Read More

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http://dx.doi.org/10.3390/cancers11111707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895914PMC
November 2019

Denovo designing: a novel signal peptide for tat translocation pathway to transport activin A to the periplasmic space of E. coli.

Biotechnol Lett 2020 Jan 2;42(1):45-55. Epub 2019 Nov 2.

Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

Objectives: The twin-arginine translocation (Tat) pathway is one of the bacterial secretory strategies which exports folded proteins across the cytoplasmic membrane.

Results: In the present study, we designed a novel Tat-signal peptide for secretion of human activin A used as a recombinant protein model here. In doing so, Haloferax volcanii, Halobacterium salinarum, and Escherichia coli Tat specific signal peptides were aligned by ClustalW program to determine conserved and more frequently used residues. Read More

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http://dx.doi.org/10.1007/s10529-019-02752-9DOI Listing
January 2020

LSD1-mediated repression of GFI1 super-enhancer plays an essential role in erythroleukemia.

Leukemia 2020 Mar 1;34(3):746-758. Epub 2019 Nov 1.

Department of Medicine, Shiga University of Medical Science, Shiga, Japan.

Super-enhancers (SEs) consist of enhancer clusters with abundant binding of transcription factors (TFs) and cofactors. LSD1 is a histone modifier that eliminates SE activity. However, whether SE suppression by LSD1 is associated with leukemogenesis remains unknown. Read More

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http://dx.doi.org/10.1038/s41375-019-0614-6DOI Listing

N-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis.

Nat Commun 2019 10 10;10(1):4596. Epub 2019 Oct 10.

Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.

Many of the regulatory features governing erythrocyte specification, maturation, and associated disorders remain enigmatic. To identify new regulators of erythropoiesis, we utilize a functional genomic screen for genes affecting expression of the erythroid marker CD235a/GYPA. Among validating hits are genes coding for the N-methyladenosine (mA) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. Read More

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http://dx.doi.org/10.1038/s41467-019-12518-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787028PMC
October 2019
1 Read

Generation of an in vitro model of β-thalassemia using the CRISPR/Cas9 genome editing system.

J Cell Biochem 2020 Feb 9;121(2):1420-1430. Epub 2019 Oct 9.

Department of Hematology and Blood Banking, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

β-Thalassemia is a common monogenic disease characterized by defective β-globin chains synthesis. In vitro β-thalassemia-related research on increasing β-like globin genes or identification of factors reducing the severity of the disease, has been performed on mouse erythroleukaemia or K562 cell lines. The aim of this study was the production of an in vitro model of β-thalassemia using the highly efficient CRISPR-Cas9 system. Read More

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http://dx.doi.org/10.1002/jcb.29377DOI Listing
February 2020
2 Reads

A natural small molecule induces megakaryocytic differentiation and suppresses leukemogenesis through activation of PKCδ/ERK1/2 signaling pathway in erythroleukemia cells.

Biomed Pharmacother 2019 Oct 21;118:109265. Epub 2019 Aug 21.

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

Kaempferol-3-O-rhamnoside (KOR) has multiple potency involved in anti-cancer, anti-inflammatory and antibacterial actions. However, the potential roles of KOR and the analogues isolated from the leaves of Cyclocarya paliurus in anti-erythroleukemia remain unclear. In the present study, KOR and the two analogues (Kaempferol-3-O-(4″-O-acetyl-a-L-rhamnopyranoside) (KLR) and (kaempferol-3-O-α-L-(4″-E-p-coumaroyl) rhamnoside) (KCR) were isolated from leaves of Cyclocarya paliurus. Read More

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http://dx.doi.org/10.1016/j.biopha.2019.109265DOI Listing
October 2019
1 Read

Flow Cytometry-Based Photodynamic Diagnosis with 5-Aminolevulinic Acid for the Detection of Minimal Residual Disease in Multiple Myeloma.

Tohoku J Exp Med 2019 09;249(1):19-28

Division of Blood Transfusion and Cell Processing, Tohoku University Hospital.

Multiple myeloma is the cancer of plasma cells. Along with the development of new and effective therapies, improved outcomes in patients with multiple myeloma have increased the interest in minimal residual disease (MRD) monitoring. However, the considerable heterogeneity of immunophenotypic and molecular markers of myeloma cells has limited its clinical application. Read More

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http://dx.doi.org/10.1620/tjem.249.19DOI Listing
September 2019
1 Read

Disease-Causing Mutations in SF3B1 Alter Splicing by Disrupting Interaction with SUGP1.

Mol Cell 2019 10 29;76(1):82-95.e7. Epub 2019 Aug 29.

Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address:

SF3B1, which encodes an essential spliceosomal protein, is frequently mutated in myelodysplastic syndromes (MDS) and many cancers. However, the defect of mutant SF3B1 is unknown. Here, we analyzed RNA sequencing data from MDS patients and confirmed that SF3B1 mutants use aberrant 3' splice sites. Read More

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http://dx.doi.org/10.1016/j.molcel.2019.07.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065273PMC
October 2019
14.018 Impact Factor

Pathologic Features of Down Syndrome Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Report From the Children's Oncology Group Protocol AAML0431.

Arch Pathol Lab Med 2020 Apr 20;144(4):466-472. Epub 2019 Aug 20.

From the Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee (Drs Mast, Mosse, Jones, and Head); the Division of Hematology/Oncology, Children's Hospital of Michigan, Wayne State University, Detroit (Dr Taub); the Department of Biostatistics, University of Southern California, Monrovia (Dr Alonzo and Mr Wang); the Division of Hematology/Oncology/Bone Marrow Transplantation, Children's Mercy Hospital, Kansas City, Missouri (Dr Gamis); the Pathology and Laboratory Medicine Service, VA Tennessee Valley Healthcare System, Nashville (Dr Mosse); the Department of Pediatrics, University of New Mexico, Albuquerque (Dr Mathew); the Division of Hematology-Oncology, IWK Health Centre, Halifax, Nova Scotia, Canada (Dr Berman); the Departments of Oncology (Dr Campana and Ms Coustan-Smith) and Pathology (Dr Raimondi), St. Jude Children's Research Hospital, Memphis, Tennessee; the Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, The National University Cancer Institute, NUH Medical Centre, Singapore (Dr Campana and Ms Coustan-Smith); the Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis (Dr Hirsch); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (Dr Hitzler); and the Division of Hematology/Oncology, The Hospital for Sick Children Developmental and Stem Cell Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada (Dr Hitzler). Dr Mast now has a joint appointment at the Pathology and Laboratory Medicine Service, VA Tennessee Valley Healthcare System, Nashville. Dr Mathew is currently at the Department of Pediatrics, Presbyterian Health Services, Albuquerque, New Mexico. Dr Berman is currently at the Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada. Dr Jones is currently at Pathgroup Labs, Nashville, Tennessee. Dr Campana is no longer at the Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. Ms Coustan-Smith is no longer at the Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Context.—: Detailed diagnostic features of acute myeloid leukemia in Down syndrome are lacking, leading to potential misdiagnoses as standard acute myeloid leukemia occurring in patients with Down syndrome.

Objective. Read More

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http://dx.doi.org/10.5858/arpa.2018-0526-OADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031019PMC
April 2020
1 Read

BCR-ABL induces tyrosine phosphorylation of YAP leading to expression of Survivin and Cyclin D1 in chronic myeloid leukemia cells.

Int J Hematol 2019 Nov 19;110(5):591-598. Epub 2019 Aug 19.

Biomedical Sciences Course, Graduate School of Life Sciences, Ritsumeikan University, Noji-Higashi, Kusatsu, Shiga, 525-8577, Japan.

In the present study, we studied downstream signals of BCR-ABL with regard to Src family kinases and YAP, a transcription cofactor and an effector of the Hippo pathway. We first checked the phosphorylation status of YAP and found that it was constitutively phosphorylated at tyrosine 357 in CML-derived cell lines (TCC-S and K562) but not in AML-derived cell lines (HL-60 and KG-1a). Treatment with imatinib or RK-20449 inhibited cell growth and decreased tyrosine phosphorylation of YAP in both CML lines. Read More

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http://dx.doi.org/10.1007/s12185-019-02726-7DOI Listing
November 2019
2 Reads

is a transcriptional target of GATA1 and drives upregulation of telomerase activity in normal human erythroblasts.

Haematologica 2020 Jun 14;105(6):1517-1526. Epub 2019 Aug 14.

Children's Cancer Institute Australia, Randwick

Telomerase is a ribonucleoprotein complex that maintains the length and integrity of telomeres, and thereby enables cellular proliferation. Understanding the regulation of telomerase in hematopoietic cells is relevant to the pathogenesis of leukemia, in which telomerase is constitutively activated, as well as bone marrow failure syndromes that feature telomerase insufficiency. Past studies showing high levels of telomerase in human erythroblasts and a prevalence of anemia in disorders of telomerase insufficiency provide the rationale for investigating telomerase regulation in erythroid cells. Read More

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http://dx.doi.org/10.3324/haematol.2018.215699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271591PMC
June 2020
3 Reads

A Human Long Non-coding RNA LncATV Promotes Virus Replication Through Restricting RIG-I-Mediated Innate Immunity.

Front Immunol 2019 19;10:1711. Epub 2019 Jul 19.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Pattern recognition receptors sense pathogen components and initiate the host antiviral innate immune response, such as inducing interferons (IFNs). Long non-coding RNAs (lncRNAs) are emerging regulators of multiple biological processes. However, their role in antiviral response, especially through regulating the human innate immune, is largely unexplored. Read More

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http://dx.doi.org/10.3389/fimmu.2019.01711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658999PMC
July 2019
3 Reads

Selective ERK1/2 agonists isolated from Melia azedarach with potent anti-leukemic activity.

BMC Cancer 2019 Aug 2;19(1):764. Epub 2019 Aug 2.

Department of Immunology State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550025, China.

Background: MAPK/ERK kinases transmit signals from many growth factors/kinase receptors during normal cell growth/differentiation, and their dysregulation is a hallmark of diverse types of cancers. A plethora of drugs were developed to block this kinase pathway for clinical application. With the exception of a recently identified agent, EQW, most of these inhibitors target upstream factors but not ERK1/2; no activator of ERK1/2 is currently available. Read More

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http://dx.doi.org/10.1186/s12885-019-5914-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679490PMC
August 2019
7 Reads

Synthesis of Flavone Derivatives via -Amination and Evaluation of Their Anticancer Activities.

Molecules 2019 Jul 26;24(15). Epub 2019 Jul 26.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.

Seventeen new flavone derivatives substituted at the 4'-OH position were designed, synthesized and evaluated for their anticancer and antibacterial activities. Among them, compounds , , , , , and demonstrated the most potent antiproliferative activities against a human erythroleukemia cell line (HEL) and a prostate cancer cell line (PC3). The results also showed that the IC value of compounds , , , , , and were close to that of the anticancer drug cisplatin (DDP) and lower than that of apigenin. Read More

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http://dx.doi.org/10.3390/molecules24152723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695693PMC
July 2019
3 Reads

MS-275 Chemical Analogues Promote Hemoglobin Production and Erythroid Differentiation of K562 Cells.

Hemoglobin 2019 Mar 7;43(2):116-121. Epub 2019 Jul 7.

a Molecular Genetics Thalassaemia Department , The Cyprus Institute of Neurology and Genetics , Nicosia , Cyprus.

β-Thalassemia (β-thal) is a hemoglobinopathy characterized by reduced or absent β-globin production. Pharmacological reactivation of the γ-globin gene for the production of fetal hemoglobin (Hb F) presents an attractive treatment strategy. In an effort to identify promising therapeutic agents, we evaluated 80 analogues of the histone deacetylase inhibitor MS-275, a known Hb F inducer. Read More

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http://dx.doi.org/10.1080/03630269.2019.1626740DOI Listing
March 2019
3 Reads

Robust CRISPR/Cas9 Genome Editing of the HUDEP-2 Erythroid Precursor Line Using Plasmids and Single-Stranded Oligonucleotide Donors.

Methods Protoc 2018 Jul 30;1(3). Epub 2018 Jul 30.

MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.

The study of cellular processes and gene regulation in terminal erythroid development has been greatly facilitated by the generation of an immortalised erythroid cell line derived from Human Umbilical Derived Erythroid Precursors, termed HUDEP-2 cells. The ability to efficiently genome edit HUDEP-2 cells and make clonal lines hugely expands their utility as the insertion of clinically relevant mutations allows study of potentially every genetic disease affecting red blood cell development. Additionally, insertion of sequences encoding short protein tags such as Strep, FLAG and Myc permits study of protein behaviour in the normal and disease state. Read More

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http://dx.doi.org/10.3390/mps1030028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481050PMC
July 2018
19 Reads

Apoptosis induction and cell cycle arrest of pladienolide B in erythroleukemia cell lines.

Invest New Drugs 2020 04 31;38(2):369-377. Epub 2019 May 31.

Laboratory of Oncobiology and Hematology, University Clinic of Hematology, Faculty of Medicine, University of Coimbra, FMUC, Azinhaga de Santa Comba-Celas, 3000-548, Coimbra, Portugal.

Splicing of pre-mRNA into functional mRNA, carried out by the spliceosome, represents a crucial step in eukaryotic gene expression. Mutations and other deregulation in some of the spliceosome components have been identified in multiple pathologies, including hematological malignancies. In this context, we evaluated the therapeutic potential of a splicing inhibitor, Pladienolide B (Pla-B), in two erythroleukemia cell lines. Read More

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http://dx.doi.org/10.1007/s10637-019-00796-2DOI Listing
April 2020
22 Reads

Organometallic rhenium tricarbonyl-enrofloxacin and -levofloxacin complexes: synthesis, albumin-binding, DNA-interaction and cell viability studies.

J Biol Inorg Chem 2019 08 20;24(5):609-619. Epub 2019 May 20.

Laboratory of Medicinal Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124, Thessaloníki, Greece.

Organometallic rhenium complexes have recently been considered in the development of novel antitumor agents due to their suitable properties. A series of rhenium(I) tricarbonyl complexes was synthesized with the quinolone antimicrobial agents enrofloxacin (Herx) and levofloxacin (Hlfx) and solvent (e.g. Read More

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http://dx.doi.org/10.1007/s00775-019-01666-1DOI Listing
August 2019
7 Reads

Hydroxyurea-induced senescent peripheral blood mesenchymal stromal cells inhibit bystander cell proliferation of JAK2V617F-positive human erythroleukemia cells.

FEBS J 2019 09 23;286(18):3647-3663. Epub 2019 May 23.

Group for Molecular Oncology, Institute for Medical Research, University of Belgrade, Serbia.

Hydroxyurea (HU) is a nonalkylating antineoplastic agent used in the treatment of hematological malignancies. HU is a DNA replication stress inducer, and as such, it may induce a premature senescence-like cell phenotype; however, its repercussion on bystander cell proliferation has not been revealed so far. Our results indicate that HU strongly inhibited peripheral blood mesenchymal stromal cells (PBMSC) proliferation by cell cycle arrest in S phase, and that, consequently, PBMSC acquire senescence-related phenotypical changes. Read More

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http://dx.doi.org/10.1111/febs.14927DOI Listing
September 2019
10 Reads

New Mechanistic Insight on the PIM-1 Kinase Inhibitor AZD1208 Using Multidrug Resistant Human Erythroleukemia Cell Lines and Molecular Docking Simulations.

Curr Top Med Chem 2019 ;19(11):914-926

Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Rio Grande - FURG, Rio Grande, RS, Brazil.

Background: PIM-1 is a kinase which has been related to the oncogenic processes like cell survival, proliferation, and multidrug resistance (MDR). This kinase is known for its ability to phosphorylate the main extrusion pump (ABCB1) related to the MDR phenotype.

Objective: In the present work, we tested a new mechanistic insight on the AZD1208 (PIM-1 specific inhibitor) under interaction with chemotherapy agents such as Daunorubicin (DNR) and Vincristine (VCR). Read More

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http://dx.doi.org/10.2174/1568026619666190509121606DOI Listing
September 2019
22 Reads

Inducible expression of immediate early genes is regulated through dynamic chromatin association by NF45/ILF2 and NF90/NF110/ILF3.

PLoS One 2019 25;14(4):e0216042. Epub 2019 Apr 25.

Pulmonary and Critical Care Medicine, Stanford University School of Medicine, Stanford, California, United States of America.

Immediate early gene (IEG) transcription is rapidly activated by diverse stimuli. This transcriptional regulation is assumed to involve constitutively expressed nuclear factors that are targets of signaling cascades initiated at the cell membrane. NF45 (encoded by ILF2) and its heterodimeric partner NF90/NF110 (encoded by ILF3) are chromatin-interacting proteins that are constitutively expressed and localized predominantly in the nucleus. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216042PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483252PMC
January 2020
7 Reads

Design, synthesis, and cytotoxic activities of novel hybrids of parthenolide and thiazolidinedione via click chemistry.

J Asian Nat Prod Res 2020 May 23;22(5):425-433. Epub 2019 Apr 23.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.

A series of novel parthenolide-thiazolidinedione hybrids have been synthesized via a click chemistry-mediated coupling between parthenolide and thiazolidinedione, and evaluated for their cytotoxic activities. The results indicated that all the hybrids showed moderate cytotoxic effects on human cancer cell lines, including human erythroleukemia cell line (HEL), prostate (PC3), and breast (MDA-MB-231) by MTT assay. In particular, compound exhibited the best cytotoxic activities against the MDA-MB-231 cells with IC value of 2. Read More

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http://dx.doi.org/10.1080/10286020.2019.1597055DOI Listing
May 2020
10 Reads

Di--lauroyl-decitabine-lipid nanocapsules: toward extending decitabine activity.

Int J Nanomedicine 2019 26;14:2091-2102. Epub 2019 Mar 26.

Micro & Nanomédecines Translationelles - MINT, UNIV Angers, INSERM 1066, CNRS 6021, University of Angers, MINT IBS-CHU, Larrey, 49933 Angers, France,

Background: Acute myeloid leukemia mainly affects adult patients. Complete remission for patients younger than 60 years, who are candidates for standard induction therapy, is achieved in 60%-80% of cases. However, the prognosis is still poor for older patients, who are unfit for intensive chemotherapy, and only a few therapies are available. Read More

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https://www.dovepress.com/di-o-lauroyl-decitabine-lipid-nano
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http://dx.doi.org/10.2147/IJN.S190482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440450PMC
May 2019
20 Reads

Growth Factor Independence 1B-Mediated Transcriptional Repression and Lineage Allocation Require Lysine-Specific Demethylase 1-Dependent Recruitment of the BHC Complex.

Mol Cell Biol 2019 07 13;39(13). Epub 2019 Jun 13.

Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA

Growth factor independence 1B (GFI1B) coordinates assembly of transcriptional repressor complexes comprised of corepressors and histone-modifying enzymes to control gene expression programs governing lineage allocation in hematopoiesis. Enforced expression of GFI1B in K562 erythroleukemia cells favors erythroid over megakaryocytic differentiation, providing a platform to define molecular determinants of binary fate decisions triggered by GFI1B. We deployed proteome-wide proximity labeling to identify factors whose inclusion in GFI1B complexes depends upon GFI1B's obligate effector, lysine-specific demethylase 1 (LSD1). Read More

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http://dx.doi.org/10.1128/MCB.00020-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580704PMC
July 2019
13 Reads

Design, synthesis and structure-activity relationship study of aminopyridine derivatives as novel inhibitors of Janus kinase 2.

Bioorg Med Chem Lett 2019 06 6;29(12):1507-1513. Epub 2019 Apr 6.

Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China. Electronic address:

Janus Kinase 2 (JAK2) is a kind of intracellular non-receptor protein tyrosine kinase and has been certified as an important target for the treatment of myeloproliferative neoplasms and rheumatoid arthritis. However, the low selectivity and potential safety issues restrict the clinical applications of JAK2 inhibitors. Here we found that crizotinib showed good inhibitory activity against JAK2 by enzymatic assays (IC = 27 nM). Read More

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http://dx.doi.org/10.1016/j.bmcl.2019.04.011DOI Listing
June 2019
11 Reads

Modulation of the spacer in N,N-bis(alkanol)amine aryl ester heterodimers led to the discovery of a series of highly potent P-glycoprotein-based multidrug resistance (MDR) modulators.

Eur J Med Chem 2019 Jun 27;172:71-94. Epub 2019 Mar 27.

Department of Neuroscience, Psychology, Drug Research and Child's Health - Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, via Ugo Schiff 6, 50019 Sesto Fiorentino (FI), Italy.

In this study, a new series of N,N-bis(alkanol)amine aryl ester heterodimers was synthesized and studied. The new compounds were designed based on the structures of our previous arylamine ester derivatives endowed with high P-gp-dependent multidrug resistance reversing activity on a multidrug-resistant leukemia cell line. All new compounds were active in the pirarubicin uptake assay on the doxorubicin-resistant erythroleukemia K562 cells (K562/DOX). Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.054DOI Listing
June 2019
8 Reads

Insertional mutagenesis using the Sleeping Beauty transposon system identifies drivers of erythroleukemia in mice.

Sci Rep 2019 04 2;9(1):5488. Epub 2019 Apr 2.

Divisions of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.

Insertional mutagenesis is a powerful means of identifying cancer drivers in animal models. We used the Sleeping Beauty (SB) transposon/transposase system to identify activated oncogenes in hematologic cancers in wild-type mice and mice that express a stabilized cyclin E protein (termed cyclin ET74AT393A). Cyclin E governs cell division and is misregulated in human cancers. Read More

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http://www.nature.com/articles/s41598-019-41805-x
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http://dx.doi.org/10.1038/s41598-019-41805-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445099PMC
April 2019
33 Reads

Recombinant Human Erythropoietin Proteins Synthesized in Escherichia coli Cells: Effects of Additional Domains on the in vitro and in vivo Activities.

Biochemistry (Mosc) 2019 Jan;84(1):20-32

Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Healthcare of the Russian Federation, Moscow, 123098, Russia.

The aim of this work was to compare biological activities of three variants of bacterially expressed human recombinant erythropoietin (EPO) with additional protein domains: 6His-s-tag-EPO protein carrying the s-tag (15-a.a. oligopeptide from bovine pancreatic ribonuclease A) at the N-terminus and HBD-EPO and EPO-HBD proteins containing heparin-binding protein domains (HBD) of the bone morphogenetic protein 2 from Danio rerio at the N- and C-termini, respectively. Read More

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http://dx.doi.org/10.1134/S0006297919010036DOI Listing
January 2019
9 Reads

Genomic subtyping and therapeutic targeting of acute erythroleukemia.

Nat Genet 2019 04 29;51(4):694-704. Epub 2019 Mar 29.

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

Acute erythroid leukemia (AEL) is a high-risk leukemia of poorly understood genetic basis, with controversy regarding diagnosis in the spectrum of myelodysplasia and myeloid leukemia. We compared genomic features of 159 childhood and adult AEL cases with non-AEL myeloid disorders and defined five age-related subgroups with distinct transcriptional profiles: adult, TP53 mutated; NPM1 mutated; KMT2A mutated/rearranged; adult, DDX41 mutated; and pediatric, NUP98 rearranged. Genomic features influenced outcome, with NPM1 mutations and HOXB9 overexpression being associated with a favorable prognosis and TP53, FLT3 or RB1 alterations associated with poor survival. Read More

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http://dx.doi.org/10.1038/s41588-019-0375-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828160PMC
April 2019
20 Reads
29.352 Impact Factor

The 2016 WHO classification of acute myeloid leukemia: What the practicing clinician needs to know.

Authors:
Daniel A Arber

Semin Hematol 2019 04 22;56(2):90-95. Epub 2018 Aug 22.

Department of Pathology, University of Chicago, Chicago, IL. Electronic address:

In 2016 a revision of the World Health Organization (WHO) classification of acute myeloid leukemia (AML) was introduced that included changes to several disease categories. The WHO approach results in disease categories that are defined by a combination of clinical, morphologic, immunophenotypic, and genetic features in an attempt to define clinically relevant, biologic entities. This review summarizes the WHO approach as well as the priority of specific features for disease classification. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00371963183009
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http://dx.doi.org/10.1053/j.seminhematol.2018.08.002DOI Listing
April 2019
23 Reads

Clinicohematologic and cytogenetic profile in a rare case of pure erythroid leukemia.

Ann Hematol 2019 Aug 11;98(8):2005-2007. Epub 2019 Mar 11.

Department of Hematopathology, Medanta - The Medicity, Sector 38, Gurgaon, 122001, India.

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http://dx.doi.org/10.1007/s00277-019-03660-8DOI Listing
August 2019
7 Reads