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Leukemia expression

Florentien E M In 't Hout, Jolanda van Duren, Davide Monteferrario, Emma Brinkhuis, Niccolo Mariani, Theresia M Westers, Dana Chitu, Gorica Nikoloski, Arjan A van de Loosdrecht, Bert A van der Reijden, Joop H Jansen, Gerwin Huls
Transcription factor 4 (TCF4) is implicated in lymphoid cell differentiation and its expression predicts outcome in acute myeloid leukemia. Here, we investigated the role of TCF4 in myelopoiesis. Overexpression of TCF4 (TCF4OE) in umbilical cord blood (UCB) cells resulted in a 2-fold increase in erythroid colony forming units (CFU-Es), while knock-down of TCF4 (TCF4KD) caused a dramatic decrease in the number of erythroid colonies. In CFU-MKs, both TCF4KD and TCF4OE inhibited megakaryocyte colony formation...
October 10, 2018: Experimental Hematology
Daniel Schuetzmann, Carolin Walter, Boet van Riel, Sabrina Kruse, Thorsten König, Tabea Erdmann, Alexander Tönges, Eric Bindels, Andre Weilemann, Claudia Gebhard, Klaus Wethmar, Chiara Perrod, Julia Minderjahn, Michael Rehli, Ruud Delwel, Georg Lenz, Stefan Gröschel, Martin Dugas, Frank Rosenbauer
Epigenetic control of gene expression occurs within discrete spatial chromosomal units called topologically associating domains (TADs), but the exact spatial requirements of most genes are unknown; this is of particular interest for genes involved in cancer. We therefore applied high-resolution chromosomal conformation capture-sequencing to map the three-dimensional (3D) organization of the human locus encoding the key myeloid transcription factor PU.1 in healthy monocytes and acute myeloid leukemia (AML) cells...
October 12, 2018: Blood
Qiyuan An, Wenkai Yan, Yi Zhao, Keqiang Yu
Rheumatoid arthritis (RA) is a high morbidity and disability disease with numerous inflammatory cells infiltrating in interstitial of articular cartilages and bones. As the most abundant inflammatory cells, neutrophil has been reported that their apoptosis changed gradually in the circumstance of RA. Apoptosis, one modality of programmed cell death (PCD), is closely associated with autophagy, which indicates neutrophil autophagy may also alter in RA. Flow cytometry, western blotting, immunohistochemistry, immunofluorescence, transmission electron microscope and multiplex antibody microarray were used to comparative investigate the status of neutrophil autophagy in patients with RA and in vitro...
October 9, 2018: International Immunopharmacology
Kentaro Ariyoshi, Tomisato Miura, Kosuke Kasai, Nakata Akifumi, Yohei Fujishima, Mitsuaki A Yoshida
Age at exposure is a critical factor that influences the risk of radiation-induced leukemia. Accumulating evidence suggests that ionizing radiation can induce genomic instability and promote leukemogenesis in hematopoietic stem cells (HSCs); however, the influence of age on this phenomenon has not been elucidated. In this study, infant (1-week-old) or adult (14-week-old) C3H/He mice received sham or 4 Gy whole-body irradiation, and bone marrow cells were transplanted to recipients at day 1 or 60 postirradiation...
October 12, 2018: Radiation Research
Lanlan Bai, Kana Yokoyama, Sonoko Watanuki, Hiroshi Ishizaki, Shin-Nosuke Takeshima, Yoko Aida
Bovine leukemia virus (BLV) is a retrovirus that causes enzootic bovine leucosis. Here, we designed a p24 enzyme-linked immunosorbent assay (ELISA) to detect antibodies specific for BLV capsid protein p24 (encoded by the gag gene) in bovine serum samples. The p24 gene was inserted into an Escherichia coli expression system, and recombinant proteins (GST-p24, p24, and His-p24) were purified. His-p24 was the most suitable antigen for using in the ELISA. The cut-off point was calculated from a receiver operating characteristic curve derived from a set of 582 field samples that previously tested positive or negative by BLV-CoCoMo-qPCR-2, which detects BLV provirus...
October 11, 2018: Archives of Virology
Waiel Al-Kahiry, Hadeel Said Tawfik, Homam Sharshira, Amal Ghanem, Maha El-Gammal, Irene Lewis Mikhael
Background: This study aimed to evaluate the prognostic value of smudge cell percentage as a surrogate marker for zeta-chain-associated protein kinase 70 (ZAP-70) expression in chronic lymphocytic leukemia (CLL) patients. Methods: Sixty three newly diagnosed CLL patients were investigated at the Hematology Department of the Medical Research Institute of Alexandria University with complete blood count, lactate dehydrogenase, β2 microglobulin levels, ZAP-70 expression, and estimation of the percentage of smudge cells...
September 2018: Blood Research
Claire Marchal, Maud de Dieuleveult, Claude Saint-Ruf, Nadège Guinot, Laure Ferry, Sara T Olalla Saad, Mariana Lazarini, Pierre-Antoine Defossez, Benoit Miotto
DNA methyltransferase inhibitor (DNMTi) treatments have been used for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and have shown promising beneficial effects in some other types of cancers. Here, we demonstrate that the transcriptional repressor ZBTB38 is a critical regulator of the cellular response to DNMTi. Treatments with 5-azacytidine, or its derivatives decitabine and zebularine, lead to down-regulation of ZBTB38 protein expression in cancer cells, in parallel with cellular damage...
October 11, 2018: Oncogenesis
Yaping Wang, Xiaoyun Yang, Xiaoyan Sun, Liucheng Rong, Meiyun Kang, Peng Wu, Xiaohui Ji, Rufeng Lin, Jie Huang, Yao Xue, Yongjun Fang
Immune escape due to immunosuppressive microenvironments, such as those associated with regulatory T (Treg) cells is highly associated with initial occurrence and development of solid tumors or hematologic malignancies. Here, we employed high-throughput transcriptome screening to demonstrate immunosuppression-associated increases in the long noncoding (lnc) RNA lnc-insulin receptor precursor (INSR), which was corrected with INSR expression in CD4+ T cells extracted from the bone marrow of patients with childhood acute T lymphoblastic leukemia...
October 11, 2018: Cell Death & Disease
Meriem Ladli, Cyrielle Richard, Lilia Cantero Aguilar, Sarah Ducamp, Sabrina Bondu, Pierre Sujobert, Jérôme Tamburini, Catherine Lacombe, Nabih Azar, Marc Foretz, Yael Zermati, Patrick Mayeux, Benoit Viollet, Frédérique Verdier
AMP-activated protein kinase is a heterotrimeric complex containing α, β, and γ subunits involved in maintaining integrity and survival of murine red blood cells (RBC). Indeed, Ampk α1-/-, Ampk b1-/- and Ampk γ1-/- mice present a hemolytic anemia and their RBC show elasticity defects in their plasma membrane. The membrane composition evolves continuously along erythropoiesis and during RBC maturation; defects due to the absence of AMPK could be initiated during erythropoiesis. Therefore, we aim to study the role of AMPK during human erythropoiesis...
October 11, 2018: Haematologica
King Pan Ng, Aditi Manjeri, Lin Ming Lee, Zhu En Chan, Chin Yee Tan, Qiancheng Darren Tan, A'Qilah Majeed, Kian Leong Lee, Charles Chuah, Toshio Suda, S Tiong Ong
Cancer cells, including in chronic myeloid leukemia (CML), depend on the hypoxic response to persist in hosts and evade therapy. Accordingly, there is significant interest in drugging cancer-specific hypoxic responses. However, a major challenge in leukemia is identifying differential and druggable hypoxic responses between leukemic and normal cells. Previously, we found that arginase 2 (ARG2), an enzyme of the urea cycle, is overexpressed in CML but not normal progenitors. ARG2 is a target of the hypoxia inducible factors (HIF1-α and HIF2-α), and is required for the generation of polyamines which are required for cell growth...
2018: PloS One
Pingyuan Wang, Jia Zhou
Great success has been achieved in small molecule drug discovery programs, making extraordinary contributions for human health, especially in targeted therapy. Taking anticancer drug discovery as an example, small molecules traditionally inhibit the target protein enzyme activities and induce cancer cell apoptosis through the target binding. However, the target protein within tumor cells often recovers its activities, leading to acquired drug-resistance through the overexpression of the target protein or the generation of new mutations in the target protein [1]...
October 9, 2018: Current Topics in Medicinal Chemistry
Chih-Peng Lin, Dai-Hua Lu
Opioid analgesics remain the most effective and widely used analgesics for the management of moderate to severe pain, including cancer pain and chronic non-cancer pain. However, the efficacy of long-term opioid analgesics is attenuated by tolerance and/or hyperalgesia after long-term use, preventing adequate pain relief under stable opioid dosages for chronic pain patients. Classical neuron-centered concepts about tolerance, such as internalization of opioid receptors, upregulation of N-methyl-D-aspartate receptor function, or downregulation of glutamate transporter activity, can only partially explain the phenomenon of tolerance...
2018: Advances in Experimental Medicine and Biology
Yibo Yin, Alina C Boesteanu, Zev A Binder, Chong Xu, Reiss A Reid, Jesse L Rodriguez, Danielle R Cook, Radhika Thokala, Kristin Blouch, Bevin McGettigan-Croce, Logan Zhang, Christoph Konradt, Alexandria P Cogdill, M Kazim Panjwani, Shuguang Jiang, Denis Migliorini, Nadia Dahmane, Avery D Posey, Carl H June, Nicola J Mason, Zhiguo Lin, Donald M O'Rourke, Laura A Johnson
We generated two humanized interleukin-13 receptor α2 (IL-13Rα2) chimeric antigen receptors (CARs), Hu07BBz and Hu08BBz, that recognized human IL-13Rα2, but not IL-13Rα1. Hu08BBz also recognized canine IL-13Rα2. Both of these CAR T cell constructs demonstrated superior tumor inhibitory effects in a subcutaneous xenograft model of human glioma compared with a humanized EGFRvIII CAR T construct used in a recent phase 1 clinical trial ( NCT02209376). The Hu08BBz demonstrated a 75% reduction in orthotopic tumor growth using low-dose CAR T cell infusion...
December 21, 2018: Molecular Therapy Oncolytics
Coralie Poulard, Estelle Baulu, Brian H Lee, Miles A Pufall, Michael R Stallcup
Synthetic glucocorticoids (GCs) are used to treat lymphoid cancers, but many patients develop resistance to treatment, especially to GC. By identifying genes that influence sensitivity to GC-induced cell death, we found that histone methyltransferases G9a and G9a-like protein (GLP), two glucocorticoid receptor (GR) coactivators, are required for GC-induced cell death in acute lymphoblastic leukemia (B-ALL) cell line Nalm6. We previously established in a few selected genes that automethylated G9a and GLP recruit heterochromatin protein 1γ (HP1γ) as another required coactivator...
October 10, 2018: Cell Death & Disease
Norio Shiba
The pathogenesis of acute myeloid leukemia (AML) is heterogeneous and caused by various chromosomal aberrations, gene mutations or epigenetic modifications, and deregulated or overregulated gene expression, leading to increased proliferation and decreased hematopoietic progenitor cell differentiation. Although most of these aberrations are correlated with prognosis, accurate risk stratification remains challenging even after incorporating these molecular markers. The development of analytical techniques using microarrays and massive parallel sequencing has identified some gene mutations in adult AML, including DNMT3A and TET2 mutations...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Kirsten M Knecht, Olga Buzovetsky, Constanze Schneider, Dominique Thomas, Vishok Srikanth, Lars Kaderali, Florentina Tofoleanu, Krystle Reiss, Nerea Ferreirós, Gerd Geisslinger, Victor S Batista, Xiaoyun Ji, Jindrich Cinatl, Oliver T Keppler, Yong Xiong
SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase (dNTPase) that depletes cellular dNTPs in noncycling cells to promote genome stability and to inhibit retroviral and herpes viral replication. In addition to being substrates, cellular nucleotides also allosterically regulate SAMHD1 activity. Recently, it was shown that high expression levels of SAMHD1 are also correlated with significantly worse patient responses to nucleotide analog drugs important for treating a variety of cancers, including acute myeloid leukemia (AML)...
October 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
Kritika Subramanian, Tim Dierckx, Ricardo Khouri, Soraya Maria Menezes, Huseini Kagdi, Graham P Taylor, Lourdes Farre, Achilea Bittencourt, Keisuke Kataoka, Seishi Ogawa, Johan Van Weyenbergh
Retinoic acid-related drugs have shown promising pre-clinical activity in Adult T-cell Leukemia/Lymphoma, but RORC signaling has not been explored. Therefore, we investigated transcriptome-wide interactions of the RORC pathway in HTLV-1 and ATL, using our own and publicly available gene expression data for ATL and other leukemias. Gene expression data from ATL patients were analyzed using WGCNA to determine gene modules and their correlation to clinical and molecular data. Both PBMCs and CD4+ T-cells showed decreased RORC expression in four different ATL cohorts...
October 10, 2018: International Journal of Cancer. Journal International du Cancer
Akiko Mori, Kunihiro Masuda, Hideo Ohtsuka, Masahiro Shijo, Kyohei Ariake, Koji Fukase, Naoaki Sakata, Masamichi Mizuma, Takanori Morikawa, Hiroki Hayashi, Kei Nakagawa, Fuyuhiko Motoi, Takeshi Naitoh, Fumiyoshi Fujishima, Michiaki Unno
The ubiquitin ligase F-box and WD repeat domain-containing 7 (FBXW7) is responsible for degrading diverse oncoproteins and is considered a tumor suppressor in many human cancers. Inhibiting FBXW7 enhances the malignant potential of several cancers. In this study, we aimed to investigate the role of FBXW7 in cholangiocarcinoma. We found that FBXW7 expression was associated with clinicopathological outcomes in cholangiocarcinoma patients. Both disease-free and overall survival were significantly worse in the low-FBXW7 group than in the high-FBXW7 group (P = 0...
October 9, 2018: Cancer Science
Preeti Gajendra Karade, Namdeo Ramhari Jadhav
Objective: The rhizome of Tectaria cicutaria has been used in Indian traditional medicine for the treatment of various disorders. The objective of present investigation is to screen various extracts of the rhizomes of Tectaria cicutaria for anti-cancer activity and to investigate the mechanism involved. Materials and methods: The rhizomes of Tectaria cicutaria were extracted with different solvents. In vitro anti-cancer activity of different rhizome extracts were studied in Human cancer Cell Lines using Sulphorodamine B (SRB) colorimetric cytotoxicity assay...
October 2018: Journal of Traditional and Complementary Medicine
Kathrin Rothfelder, Ilona Hagelstein, Malte Roerden, Gunnar Blumenstock, Martin Hofmann, Tina Nuebling, Gundram Jung, Helmut Rainer Salih, Daniela Dörfel
OX40 and its ligand are members of the TNF/TNF receptor superfamily, which includes various molecules influencing cellular signaling and function of both tumor and immune cells. The ability of OX40 to promote proliferation and differentiation of activated T cells fueled present attempts to modulate this immune checkpoint to reinforce antitumor immunity. While we recently found evidence for the involvement of OX40 in pathophysiology of acute myeloid leukemia including natural killer (NK) cell immunosurveillance, less is known on its role in acute lymphoblastic leukemia (ALL)...
October 6, 2018: Neoplasia: An International Journal for Oncology Research
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