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https://www.readbyqxmd.com/read/28300275/iron-chelation-therapy-in-low-risk-myelodysplastic-syndrome
#1
REVIEW
Sally B Killick
Anaemia is the commonest cytopenia seen in patients with myelodysplastic syndrome (MDS), and the majority of patients will require transfusion support at some point. Blood transfusions are rich in iron, which leads to the accumulation of body iron over time. It is accepted that this ultimately causes end organ damage and may impact on both morbidity and mortality. In addition, recent data has increased our interest in the subject with regard to the potential impact on stem cell transplant outcome and an anti-leukaemic effect of iron chelation therapy...
March 16, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28266526/elf-mf-exposure-affects-the-robustness-of-epigenetic-programming-during-granulopoiesis
#2
Melissa Manser, Mohamad R Abdul Sater, Christoph D Schmid, Faiza Noreen, Manuel Murbach, Niels Kuster, David Schuermann, Primo Schär
Extremely-low-frequency magnetic fields (ELF-MF) have been classified as "possibly carcinogenic" to humans on the grounds of an epidemiological association of ELF-MF exposure with an increased risk of childhood leukaemia. Yet, underlying mechanisms have remained obscure. Genome instability seems an unlikely reason as the energy transmitted by ELF-MF is too low to damage DNA and induce cancer-promoting mutations. ELF-MF, however, may perturb the epigenetic code of genomes, which is well-known to be sensitive to environmental conditions and generally deranged in cancers, including leukaemia...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28165036/the-promotion-of-erythropoiesis-via-the-regulation-of-reactive-oxygen-species-by-lactic-acid
#3
Shun-Tao Luo, Dong-Mei Zhang, Qing Qin, Lian Lu, Min Luo, Fu-Chun Guo, Hua-Shan Shi, Li Jiang, Bin Shao, Meng Li, Han-Shuo Yang, Yu-Quan Wei
The simultaneous increases in blood lactic acid and erythrocytes after intense exercise could suggest a link between lactate and the erythropoiesis. However, the effects of lactic acid on erythropoiesis remain to be elucidated. Here, we utilized a mouse model to determine the role of lactic acid in this process in parallel with studies using leukaemic K562 cells. Treatment of K562 cells in vitro with lactic acid increased the mRNA and protein expression of haemoglobin genes and the frequency of GPA(+) cells...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28159740/the-chronic-myeloid-leukemia-stem-cell-stemming-the-tide-of-persistence
#4
Tessa L Holyoake, David Vetrie
Chronic myeloid leukaemia (CML) is caused by the acquisition of the tyrosine kinase BCR-ABL1 in a haemopoietic stem cell (HSC), transforming it into a leukaemic stem cell (LSC) that self-renews, proliferates and differentiates to give rise to a myeloproliferative disease. While tyrosine kinase inhibitors (TKI) that target the kinase activity of BCR-ABL1 have transformed CML from a once fatal disease to a manageable one for the vast majority of patients, only ~10% of those who present in chronic phase (CP) can discontinue TKI treatment and maintain a therapy-free remission...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28146632/antibody-targeted-cyclodextrin-based-nanoparticles-for-sirna-delivery-in-the-treatment-of-acute-myeloid-leukemia-physicochemical-characteristics-in-vitro-mechanistic-studies-and-ex-vivo-patient-derived-therapeutic-efficacy
#5
Jianfeng Guo, Eileen G Russell, Raphael Darcy, Thomas G Cotter, Sharon L McKenna, Mary R Cahill, Caitriona M O'Driscoll
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and is associated with high relapse rates. It is known that leukemia stem cells (LSCs), a very small subpopulation of the total number of leukemic cells, maintain the leukemia phenotype (∼80-90% of AML remain the same as at first diagnosis), display chemotherapy resistance, and contribute to disease regeneration. Therefore, targeting LSCs could control the relapse of AML. Small interfering RNA (siRNA), an effector of the RNA interference (RNAi) pathway, can selectively downregulate any gene implicated in the pathology of disease, presenting great potential for treatment of AML...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28114130/identifying-cardiovascular-risk-in-survivors-of-childhood-leukaemia-treated-with-haematopoietic-stem-cell-transplantation-and-total-body-irradiation%C3%A2
#6
Christina Wei, Linda Hunt, Rachel Cox, Karin Bradley, Ruth Elson, Julian Shield, Michael Stevens, Elizabeth Crowne
BACKGROUND: Survivors of childhood with haematopoietic stem cell transplantation and total body irradiation (HSCT/TBI) have an increased cardiometabolic risk without overt obesity. AIM: To describe cardiometabolic risk in HSCT/TBI survivors and identify anthropometric measurements of adiposity representative of cardiometabolic risks in HSCT/TBI survivors. METHOD: Childhood leukaemia survivors treated with HSCT/TBI (n = 21, 11 males) were compared with chemotherapy-only (n = 31) and obese non-leukaemic controls (n = 30)...
January 23, 2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/28064238/myeloid-malignancies-and-the-microenvironment
#7
REVIEW
Claudia Korn, Simón Méndez-Ferrer
Research in the last few years has revealed a sophisticated interaction network between multiple bone marrow cells that regulate different hematopoietic stem cell (HSC) properties such as proliferation, differentiation, localization, and self-renewal during homeostasis. These mechanisms are essential to keep the physiological HSC numbers in check and interfere with malignant progression. In addition to the identification of multiple mutations and chromosomal aberrations driving the progression of myeloid malignancies, alterations in the niche compartment recently gained attention for contributing to disease progression...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28008858/refractory-leukaemic-cutaneous-cd3-tcr-phenotype-t-cell-lymphoma-with-complete-remission-after-allogeneic-stem-cell-transplantation
#8
Hatice Şanlı, Bengü Nisa Akay, Seçil Saral, Aylin Okçu Heper, Pervin Topçuoğlu
No abstract text is available yet for this article.
December 23, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/27911727/role-of-the-bone-morphogenic-protein-pathway-in-developmental-haemopoiesis-and-leukaemogenesis
#9
REVIEW
Parto Toofan, Helen Wheadon
Myeloid leukaemias share the common characteristics of being stem cell-derived clonal diseases, characterised by excessive proliferation of one or more myeloid lineage. Chronic myeloid leukaemia (CML) arises from a genetic alteration in a normal haemopoietic stem cell (HSC) giving rise to a leukaemic stem cell (LSC) within the bone marrow (BM) 'niche'. CML is characterised by the presence of the oncogenic tyrosine kinase fusion protein breakpoint cluster region-abelson murine leukaemia viral oncogene homolog 1 (BCR-ABL), which is responsible for driving the disease through activation of downstream signal transduction pathways...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27884555/after-10years-of-jak2v617f-disease-biology-and-current-management-strategies-in-polycythaemia-vera
#10
REVIEW
Jacob Grinfeld, Anna L Godfrey
The JAK2V617F mutation accounts for the vast majority of patients with polycythaemia vera (PV) and around half of those with other Philadelphia-negative myeloproliferative neoplasms. Since its discovery in 2005, numerous insights have been gained into the pathways by which JAK2V617F causes myeloproliferation, including activation of JAK-STAT signalling but also through other canonical and non-canonical pathways. A variety of mechanisms explain how this one mutation can be associated with distinct clinical disorders, demonstrating how constitutional and acquired factors may interact in the presence of a single mutation to determine disease phenotype...
November 15, 2016: Blood Reviews
https://www.readbyqxmd.com/read/27783593/leukaemogenic-effects-of-ptpn11-activating-mutations-in-the-stem-cell-microenvironment
#11
Lei Dong, Wen-Mei Yu, Hong Zheng, Mignon L Loh, Silvia T Bunting, Melinda Pauly, Gang Huang, Muxiang Zhou, Hal E Broxmeyer, David T Scadden, Cheng-Kui Qu
Germline activating mutations of the protein tyrosine phosphatase SHP2 (encoded by PTPN11), a positive regulator of the RAS signalling pathway, are found in 50% of patients with Noonan syndrome. These patients have an increased risk of developing leukaemia, especially juvenile myelomonocytic leukaemia (JMML), a childhood myeloproliferative neoplasm (MPN). Previous studies have demonstrated that mutations in Ptpn11 induce a JMML-like MPN through cell-autonomous mechanisms that are dependent on Shp2 catalytic activity...
November 10, 2016: Nature
https://www.readbyqxmd.com/read/27665785/arsenic-trioxide-potentiates-the-effectiveness-of-etoposide-in-ewing-sarcomas
#12
Karen A Boehme, Juliane Nitsch, Rosa Riester, Rupert Handgretinger, Sabine B Schleicher, Torsten Kluba, Frank Traub
Ewing sarcomas (ES) are rare mesenchymal tumours, most commonly diagnosed in children and adolescents. Arsenic trioxide (ATO) has been shown to efficiently and selectively target leukaemic blasts as well as solid tumour cells. Since multidrug resistance often occurs in recurrent and metastatic ES, we tested potential additive effects of ATO in combination with the cytostatic drugs etoposide and doxorubicin. The Ewing sarcoma cell lines A673, RD-ES and SK-N-MC as well as mesenchymal stem cells (MSC) for control were treated with ATO, etoposide and doxorubicin in single and combined application...
November 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27612176/unravelling-the-relevance-of-clec12a-as-a-cancer-stem-cell-marker-in-myelodysplastic-syndrome
#13
Marie Toft-Petersen, Line Nederby, Eigil Kjeldsen, Gitte B Kerndrup, Gordon D Brown, Peter Hokland, Anne Stidsholt Roug
Evidence of distinct disease propagating stem cells in myelodysplastic syndrome (MDS) has emerged in recent years. However, immunophenotypic characterization of these cancer stem cells remains sparse. In acute myeloid leukaemia (AML), we have previously described aberrant expression of the C-type lectin domain family 12, member A (CLEC12A) as a stable and reliable marker of leukaemia blasts and as a tool for assessing minimal residual disease. Furthermore, CLEC12A has been proposed as a promising marker of leukaemic stem cells in AML...
November 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27604872/a-quantitative-proteomics-approach-identifies-etv6-and-ikzf1-as-new-regulators-of-an-erg-driven-transcriptional-network
#14
Ashwin Unnikrishnan, Yi F Guan, Yizhou Huang, Dominik Beck, Julie A I Thoms, Sofie Peirs, Kathy Knezevic, Shiyong Ma, Inge V de Walle, Ineke de Jong, Zara Ali, Ling Zhong, Mark J Raftery, Tom Taghon, Jonas Larsson, Karen L MacKenzie, Pieter Van Vlierberghe, Jason W H Wong, John E Pimanda
Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-ALL and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic cells remains poorly understood. In order to discover transcriptional regulators of ERG, we employed a quantitative mass spectrometry-based method to identify factors binding the 321 bp ERG +85 stem cell enhancer region in MOLT-4 T-ALL and KG-1 AML cells...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27602789/cytokine-release-patterns-in-mixed-lymphocyte-culture-mlc-of-t-cells-with-dendritic-cells-dc-generated-from-aml-blasts-contribute-to-predict-anti-leukaemic-t-cell-reactions-and-patients-response-to-immunotherapy
#15
Dorothea Fischbacher, Marion Merle, Anja Liepert, Christine Grabrucker, Tanja Kroell, Andreas Kremser, Julia Dreyßig, Markus Freudenreich, Friedhelm Schuster, Arndt Borkhardt, Doris Kraemer, Claus-Henning Koehne, Hans-Jochem Kolb, Christoph Schmid, Helga Maria Schmetzer
To enlighten interactions between autologous, allogeneic or T-cells from patients after stem cell transplantation with leukaemia-derived-dendritic-cells containing dendritic cells or blast containing mononuclear cells (n = 21, respectively), we determined cytokine-concentrations (interleukin 2, 4, 6, 10, tumor-necrosis-factor-α, interferon-γ) in supernatants of mixed-lymphocyte-culture and in serum (n = 16) of 20 patients with acute myeloid leukaemia and three patients with myelodysplastic syndromes by cytometric-bead-assay...
April 2015: Cell Communication & Adhesion
https://www.readbyqxmd.com/read/27473566/tunnelling-nanotubes-mediate-the-transfer-of-stem-cell-marker-cd133-between-haematopoietic-progenitor-cells
#16
Doreen Reichert, Julia Scheinpflug, Jana Karbanová, Daniel Freund, Martin Bornhäuser, Denis Corbeil
Deciphering all mechanisms of intercellular communication used by haematopoietic progenitors is important, not only for basic stem cell research, but also in view of their therapeutic relevance. Here, we investigated whether these cells can produce thin F-actin-based plasma membrane protrusions, referred to as tunnelling nanotubes (TNTs), which are known to bridge cells over long distances without contact with the substratum, and transfer cargo molecules along them in various biological processes. We found that human primary CD34(+) haematopoietic progenitors and leukaemic KG1a cells develop such structures upon culture on primary mesenchymal stromal cells or specific extracellular matrix-based substrata...
July 26, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27411711/stem-cell-guardians-old-and-new-perspectives-in-lsc-biology
#17
Gillian A Horne, Lorna Jackson, Vignir Helgason, Tessa L Holyoake
The introduction of tyrosine kinase inhibitors in chronic myeloid leukaemia (CML) has revolutionised disease outcome. However, despite this, progression to blast phase disease is high in those that do not achieve complete cytogenetic and major molecular response on standard therapy. As well as BCR-ABL-dependent mechanisms, disease persistence has been shown to play a key role. Disease persistence suggests that, despite a targeted therapeutic approach, BCR-ABL-independent mechanisms are being exploited to sustain the survival of a small population of cells termed leukaemic stem cells (LSCs)...
2017: Current Drug Targets
https://www.readbyqxmd.com/read/27341144/negative-regulation-of-tim-3-expression-in-aml-cell-line-hl-60-using-mir-330-5p
#18
Haniyeh Fooladinezhad, Hossein Khanahmad, Mazdak Ganjalikhani-Hakemi, Abbas Doosti
BACKGROUND: Uncontrolled proliferation and accumulation of leukaemic stem cells (LSCs) in bone marrow leads to acute myeloma leukaemia (AML). T cell immunoglobulin and mucine domain (TIM)-3 is a specific surface marker for LSCs and is highly expressed on LSCs compared with normal bone marrow cells, haematopoietic stem cells. Studies have indicated that microRNAs can affect AML progression through targeting different genes expressions like TIM-3. So, based on bioinformatics assessments, we predicted that miR-330-5p may highly inhibit TIM-3 expression...
July 2016: British Journal of Biomedical Science
https://www.readbyqxmd.com/read/27281222/dual-targeting-of-p53-and-c-myc-selectively-eliminates-leukaemic-stem-cells
#19
Sheela A Abraham, Lisa E M Hopcroft, Emma Carrick, Mark E Drotar, Karen Dunn, Andrew J K Williamson, Koorosh Korfi, Pablo Baquero, Laura E Park, Mary T Scott, Francesca Pellicano, Andrew Pierce, Mhairi Copland, Craig Nourse, Sean M Grimmond, David Vetrie, Anthony D Whetton, Tessa L Holyoake
Chronic myeloid leukaemia (CML) arises after transformation of a haemopoietic stem cell (HSC) by the protein-tyrosine kinase BCR-ABL. Direct inhibition of BCR-ABL kinase has revolutionized disease management, but fails to eradicate leukaemic stem cells (LSCs), which maintain CML. LSCs are independent of BCR-ABL for survival, providing a rationale for identifying and targeting kinase-independent pathways. Here we show--using proteomics, transcriptomics and network analyses--that in human LSCs, aberrantly expressed proteins, in both imatinib-responder and non-responder patients, are modulated in concert with p53 (also known as TP53) and c-MYC regulation...
June 16, 2016: Nature
https://www.readbyqxmd.com/read/27130156/three-dimensional-ex-vivo-co-culture-models-of-the-leukaemic-bone-marrow-niche-for-functional-drug-testing
#20
REVIEW
Sukhraj Pal S Dhami, Shanthi S Kappala, Alexander Thompson, Eva Szegezdi
Acute myeloid leukaemia (AML) is a hierarchically structured malignancy in which aberrant leukemic stem cells drive the production of leukaemic blast cell clones. AML cells strictly depend on the bone marrow microenvironment (BMM) in which they reside. Classical AML cell cultures fail to mimic the BMM and, therefore, drug discovery studies are dominated by in vivo models. However, animal models are time consuming, labour intensive, provide limited mechanistic insight, and are unsuited for high-throughput studies, necessitating the development of novel AML models...
September 2016: Drug Discovery Today
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