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https://www.readbyqxmd.com/read/28535394/red-blood-cell-alloimmunization-in-184-patients-with-myeloid-neoplasms-treated-with-azacitidine-a-retrospective-single-center-experience
#1
M Leisch, L Weiss, N Lindlbauer, C Jungbauer, A Egle, E Rohde, R Greil, C Grabmer, L Pleyer
Alloimmunization to Red Blood Cell (RBC) antigens frequently occurs in patients with myeloid neoplasms (AML, MDS and CMML) and potentially poses the patient at risk for delayed hemolytic transfusion reactions and limited supply of compatible RBC-units. However, there is comparatively little data on transfusion associated characteristics in this patient cohort. We therefore retrospectively analyzed transfusion requirements and clinical outcomes of 184 patients with myloid neoplasms treated with azacitidine at the Paracelsus Medical University Salzburg, which were included in the Austrian Registry of Hypomethylating Agents...
May 9, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28535153/high-energy-particle-beam-and-gamma-radiation-exposure-familial-relatedness-and-cancer-in-mice
#2
Pavel Chernyavskiy, Elijah F Edmondson, Michael M Weil, Mark P Little
BACKGROUND: Some highly penetrant familial cancer syndromes exhibit elevated leukaemia risk, and there is evidence for familial clustering of lung cancer and other common cancers. Lung cancer and leukaemia are strongly radiogenic, but there are few indications that high-energy beam irradiation is markedly more effective than lower-energy radiation. METHODS: We used a Cox model with familially structured random effects to assess 16 mortality end points in a group of 1850 mice in 47 families maintained in a circular-breeding scheme, exposed to accelerated Si or Fe ions (0...
May 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28535011/tumor-growth-limited-to-subcutaneous-site-vs-tumor-growth-in-pulmonary-site-exhibit-differential-effects-on-systemic-immunities
#3
Junko Masuda, Eiji Takayama, Warren Strober, Ayano Satoh, Yuji Morimoto, Yasuko Honjo, Tatsuo Ichinohe, Shin-Ichi Tokuno, Toshiaki Ishizuka, Takahiro Nakata, Akifumi Mizutani, Naoki Umemura, Atsushi Kitani, Ivan J Fuss, Tsukasa Shigehiro, Harumi Kawaki, Masako Mizuno-Kamiya, Nobuo Kondoh, Masaharu Seno
To evaluate systemic immunity associated with tumor growth limited to a subcutaneous site versus growth proceeding at multiple tumor sites, we established syngeneic mouse subcutaneous and pulmonary tumor models by local subcutaneous and intravenous injection of colon carcinoma CT26 cells. We found that splenic myeloid-derived suppressor cell (MDSC) levels were significantly increased in the subcutaneous tumor model but not in the pulmonary tumor model. Furthermore, both CD4+ and CD8+ T cells as well as CD4+ Foxp3+ T cells were significantly decreased in the subcutaneous tumor model and were largely unchanged in the pulmonary tumor model...
May 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534709/mdscs-are-involved-in-the-protumorigenic-potentials-of-gm-csf-in-colitis-associated-cancer
#4
Ning Ma, Qilin Liu, Lin Hou, Yalin Wang, Ziling Liu
Chronic inflammation is thought to be a major driving force for the development of colitis-associated colorectal cancer (CAC). As one member of proinflammatory cytokine family, granulocyte macrophage colony-stimulating factor (GM-CSF) has been identified to play a key role in CAC pathogenesis recently. The underlying mechanisms, however, remain largely unknown. In this study, we found that myeloid-derived suppressor cells (MDSCs) accumulated increasingly in the lesions during the progression from colitis to cancer, which was critical for CAC formation...
May 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28534246/microglia-housekeeper-of-the-central-nervous-system
#5
REVIEW
John Alimamy Kabba, Yazhou Xu, Handson Christian, Wenchen Ruan, Kitchen Chenai, Yun Xiang, Luyong Zhang, Juan M Saavedra, Tao Pang
Microglia, of myeloid origin, play fundamental roles in the control of immune responses and the maintenance of central nervous system homeostasis. These cells, just like peripheral macrophages, may be activated into M1 pro-inflammatory or M2 anti-inflammatory phenotypes by appropriate stimuli. Microglia do not respond in isolation, but form part of complex networks of cells influencing each other. This review addresses the complex interaction of microglia with each cell type in the brain: neurons, astrocytes, cerebrovascular endothelial cells, and oligodendrocytes...
May 22, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28534184/evaluation-of-cardiovascular-ischemic-event-rates-in-dasatinib-treated-patients-using-standardized-incidence-ratios
#6
Giuseppe Saglio, Philipp le Coutre, Jorge Cortes, Jiří Mayer, Philip Rowlings, François-Xavier Mahon, Glenn Kroog, Kyna Gooden, Milayna Subar, Neil P Shah
With high survival rates for chronic myeloid leukemia (CML) patients treated with BCR-ABL1 tyrosine kinase inhibitors (TKIs), emerging consequences, such as arterial ischemic events, require consideration when evaluating treatment options. Cardiovascular ischemic event incidence in clinical trials was evaluated in 2712 dasatinib-treated patients with Philadelphia chromosome-positive (Ph+) leukemias from 11 first- and second-line trials (pooled), newly diagnosed CML patients treated with dasatinib or imatinib (DASISION), and prostate cancer patients treated with dasatinib or placebo plus docetaxel/prednisone (READY)...
May 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28534116/myeloid-neoplasms-with-germ-line-runx1-mutation
#7
REVIEW
Yoshihiro Hayashi, Yuka Harada, Gang Huang, Hironori Harada
Familial platelet disorder with propensity to myeloid malignancies (FPD/AML) is an autosomal dominant disorder characterized by quantitative and/or qualitative platelet defects with a tendency to develop a variety of hematological malignancies. Heterozygous germ line mutations in the RUNX1 gene are responsible genetic events for FPD/AML. Notably, about half of individuals in the family with germ line mutations in RUNX1 develop overt hematological malignancies. The latency is also relatively long as an average age at diagnosis is more than 30 years...
May 22, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28533822/chemotherapy-induced-hypomethylation-of-n-myc-downstream-regulated-gene-4-in-the-bone-marrow-of-patients-with-acute-myeloid-leukemia
#8
Qingxiao Hong, Xiaoying Chen, Huadan Ye, Xiaodong Wu, Xuejing Wang, Lingyan Kong, Yongming Xia, Shiwei Duan
N-myc downstream-regulated gene 4 (NDRG4) has previously been investigated as a possible tumor suppressor. Hypermethylation of tumor suppressor genes contributes to the occurrence and development of certain types of cancer, including acute myeloid leukemia (AML). The current study aimed to assess the contribution of chemotherapy-induced NDRG4 changeable methylation to the development of AML. A total of 30 patients (13 males and 17 females) were involved in the present study. The DNA methylation levels of five C-phosphate-G sites of the NDRG4 gene were measured using bisulfite pyrosequencing techniques...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28533818/a-novel-bcr-abl1-fusion-gene-with-genetic-heterogeneity-indicates-a-good-prognosis-in-a-chronic-myeloid-leukemia-case
#9
Fen Zhou, Runming Jin, Yu Hu, Heng Mei
BACKGROUND: Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28533480/deregulated-expression-of-mir-29a-3p-mir-494-3p-and-mir-660-5p-affects-sensitivity-to-tyrosine-kinase-inhibitors-in-cml-leukemic-stem-cells
#10
Simona Salati, Valentina Salvestrini, Chiara Carretta, Elena Genovese, Sebastiano Rontauroli, Roberta Zini, Chiara Rossi, Samantha Ruberti, Elisa Bianchi, Greta Barbieri, Antonio Curti, Fausto Castagnetti, Gabriele Gugliotta, Gianantonio Rosti, Micaela Bergamaschi, Agostino Tafuri, Enrico Tagliafico, Roberto Lemoli, Rossella Manfredini
The development of Imatinib mesylate (IM), which targets the oncogenic BCR-ABL fusion protein, has greatly improved the outcome of Chronic Myeloid Leukemia (CML) patients. However, BCR-ABL-positive progenitors can be detected in CML patients in complete cytogenetic response. Several evidence suggests that CML stem cells are intrinsically resistant to Tyrosine Kinase Inhibitors (TKI), and therefore they represent the most likely candidate responsible for disease relapse.In this work, we investigated the microRNA (miRNA) expression profile of different subpopulations of CML Leukemic Stem Cells (LSCs): Lin-CD34+CD38- and Lin-CD34-CD38- cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533469/the-phenotype-and-function-of-myeloid-derived-suppressor-cells-induced-by-porphyromonas-gingivalis-infection
#11
Lingkai Su, Qingan Xu, Ping Zhang, Suzanne M Michalek, Jannet Katz
Porphyromonas gingivalis (Pg), a major etiologic agent of periodontitis, has been reported to induce the expansion of myeloid-derived suppressor cells (MDSC); however, little is known regarding the subpopulations of MDSC expanded by Pg infection. Flow cytometry was used to evaluate bone marrow and spleen cells from mice infected with Pg and controls for surface expression of CD11b, Ly6G and Ly6C. To characterize the phenotype of MDSC subpopulations induced by infection, cells were sorted based on the differential expression of Ly6G and Ly6C...
May 22, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28533407/histone-binding-of-dpf2-mediates-its-repressive-role-in-myeloid-differentiation
#12
Ferdinand M Huber, Sarah M Greenblatt, Andrew M Davenport, Concepcion Martinez, Ye Xu, Ly P Vu, Stephen D Nimer, André Hoelz
Double plant homeodomain finger 2 (DPF2) is a highly evolutionarily conserved member of the d4 protein family that is ubiquitously expressed in human tissues and was recently shown to inhibit the myeloid differentiation of hematopoietic stem/progenitor and acute myelogenous leukemia cells. Here, we present the crystal structure of the tandem plant homeodomain finger domain of human DPF2 at 1.6-Å resolution. We show that DPF2 interacts with the acetylated tails of both histones 3 and 4 via bipartite binding pockets on the DPF2 surface...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533390/prognostic-and-biological-significance-of-the-proangiogenic-factor-egfl7-in-acute-myeloid-leukemia
#13
Dimitrios Papaioannou, Changxian Shen, Deedra Nicolet, Betina McNeil, Marius Bill, Malith Karunasiri, Matthew H Burke, Hatice Gulcin Ozer, Selen A Yilmaz, Nina Zitzer, Gregory K Behbehani, Christopher C Oakes, Damian J Steiner, Guido Marcucci, Bayard L Powell, Jonathan E Kolitz, Thomas H Carter, Eunice S Wang, Krzysztof Mrózek, Carlo M Croce, Michael A Caligiuri, Clara D Bloomfield, Ramiro Garzon, Adrienne M Dorrance
Epithelial growth factor-like 7 (EGFL7) is a protein that is secreted by endothelial cells and plays an important role in angiogenesis. Although EGFL7 is aberrantly overexpressed in solid tumors, its role in leukemia has not been evaluated. Here, we report that levels of both EGFL7 mRNA and EGFL7 protein are increased in blasts of patients with acute myeloid leukemia (AML) compared with normal bone marrow cells. High EGFL7 mRNA expression associates with lower complete remission rates, and shorter event-free and overall survival in older (age ≥60 y) and younger (age <60 y) patients with cytogenetically normal AML...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533357/tlr9-expression-and-secretion-of-lif-by-prostate-cancer-cells-stimulates-accumulation-and-activity-of-polymorphonuclear-mdscs
#14
Haejung Won, Dayson Moreira, Chan Gao, Priyanka Duttagupta, Xingli Zhao, Edwin Manuel, Don Diamond, Yate-Ching Yuan, Zheng Liu, Jeremy Jones, Massimo D'Apuzzo, Sumanta Pal, Marcin Kortylewski
Proinflammatory signals promote prostate tumorigenesis and progression, but their origins and downstream effects remain unclear. We recently demonstrated that the expression of an innate immune receptor, TLR9, by prostate cancer cells is critical for their tumor-propagating potential. We investigated whether cancer cell-intrinsic TLR9 signaling alters composition of the prostate tumor microenvironment. We generated Ras/Myc (RM9) and Myc-driven (Myc-CaP) prostate cancer cells expressing the tetracycline-inducible gene Tlr9 (Tlr9(ON) ) or the control LacZ (LacZ(ON) )...
May 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28533061/comparison-of-autologous-and-unrelated-transplants-for-cytogenetically-normal-acute-myeloid-leukemia
#15
Motonori Mizutani, Akiyoshi Takami, Masahiko Hara, Shohei Mizuno, Masamitsu Yanada, Takaaki Chou, Hitoji Uchiyama, Kazuteru Ohashi, Toshihiro Miyamoto, Yukiyasu Ozawa, Osamu Imataki, Naoki Kobayashi, Naoyuki Uchida, Heiwa Kanamori, Tomohiko Kamimura, Tetsuya Eto, Makoto Onizuka, Junji Tanaka, Yoshiko Atsuta, Shingo Yano
Allogeneic stem cell transplantation (SCT) from an HLA-matched sibling donor (MSD) is a post-remission treatment that offers a potential cure for adults with cytogenetically normal acute myeloid leukemia in their first complete remission (CN-AML/CR1). However, the best alternative in the absence of an MSD remains unclear. The aim of this study was to retrospectively compare the outcomes of autologous peripheral blood stem cell transplantation (auto-PBSCT; n = 177) to those of allogeneic bone marrow transplantation from an HLA-matched unrelated donor (MUD-BMT; n = 173) in adult patients with CN-AML/CR1...
May 19, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28530640/genetic-regulation-of-the-runx-transcription-factor-family-has-antitumor-effects
#16
Ken Morita, Kensho Suzuki, Shintaro Maeda, Akihiko Matsuo, Yoshihide Mitsuda, Chieko Tokushige, Gengo Kashiwazaki, Junichi Taniguchi, Rina Maeda, Mina Noura, Masahiro Hirata, Tatsuki Kataoka, Ayaka Yano, Yoshimi Yamada, Hiroki Kiyose, Mayu Tokumasu, Hidemasa Matsuo, Sunao Tanaka, Yasushi Okuno, Manabu Muto, Kazuhito Naka, Kosei Ito, Toshio Kitamura, Yasufumi Kaneda, Paul P Liu, Toshikazu Bando, Souichi Adachi, Hiroshi Sugiyama, Yasuhiko Kamikubo
Runt-related transcription factor 1 (RUNX1) is generally considered to function as a tumor suppressor in the development of leukemia, but a growing body of evidence suggests that it has pro-oncogenic properties in acute myeloid leukemia (AML). Here we have demonstrated that the antileukemic effect mediated by RUNX1 depletion is highly dependent on a functional p53-mediated cell death pathway. Increased expression of other RUNX family members, including RUNX2 and RUNX3, compensated for the antitumor effect elicited by RUNX1 silencing, and simultaneous attenuation of all RUNX family members as a cluster led to a much stronger antitumor effect relative to suppression of individual RUNX members...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28530125/pro-inflammatory-activation-of-primary-microglia-and-macrophages-increases-18%C3%A2-kda-translocator-protein-expression-in-rodents-but-not-humans
#17
David R Owen, Nehal Narayan, Lisa Wells, Luke Healy, Erica Smyth, Eugenii A Rabiner, Dylan Galloway, John B Williams, Joshua Lehr, Harpreet Mandhair, Laura An Peferoen, Peter C Taylor, Sandra Amor, Jack P Antel, Paul M Matthews, Craig S Moore
The 18kDa Translocator Protein (TSPO) is the most commonly used tissue-specific marker of inflammation in positron emission tomography (PET) studies. It is expressed in myeloid cells such as microglia and macrophages, and in rodent myeloid cells expression increases with cellular activation. We assessed the effect of myeloid cell activation on TSPO gene expression in both primary human and rodent microglia and macrophages in vitro, and also measured TSPO radioligand binding with (3)H-PBR28 in primary human macrophages...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28529930/the-central-role-of-ifi204-in-ifn-%C3%AE-release-and-autophagy-activation-during-mycobacterium-bovis-infection
#18
Liu Chunfa, Sun Xin, Li Qiang, Srinand Sreevatsan, Lifeng Yang, Deming Zhao, Xiangmei Zhou
Mycobacterium bovis (M. bovis) is the pathogen of animals and humans that can replicate in the phagosomes of myeloid cells. Cytosolic detection of bacterial products plays a crucial role in initiating the innate immune response, including autophagy activation and interferon-β (IFN-β) release. Although IFN-β release and autophagy activation have been reported during mycobacterium infection, the mechanisms underlying remains poorly defined. Here, we demonstrated that IFN-β release increases in macrophages exposed to M...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28529810/molecular-profiling-a-case-of-zbtb16-rara-acute-promyelocytic-leukemia
#19
Stephen E Langabeer, Lisa Preston, Johanna Kelly, Matt Goodyer, Ezzat Elhassadi, Amjad Hayat
Several variant RARA translocations have been reported in acute promyelocytic leukemia (APL) of which the t(11;17)(q23;q21), which results in a ZBTB16-RARA fusion, is the most widely identified and is largely resistant to therapy with all-trans retinoic acid (ATRA). The clinical course together with the cytogenetic and molecular characterization of a case of ATRA-unresponsive ZBTB16-RARA APL is described. Additional mutations potentially cooperating with the translocation fusion product in leukemogenesis have been hitherto unreported in ZBTB16-RARA APL and were sought by application of a next-generation sequencing approach to detect those recurrently found in myeloid malignancies...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28529313/impact-of-killer-immunoglobulin-like-receptor-and-human-leukocyte-antigen-genotypes-on-the-efficacy-of-immunotherapy-in-acute-myeloid-leukemia
#20
E Bernson, A Hallner, F E Sander, O Wilsson, O Werlenius, A Rydström, R Kiffin, M Brune, R Foà, J Aurelius, A Martner, K Hellstrand, F B Thorén
Interactions between killer-immunoglobulin-like receptors (KIRs) and their HLA class I ligands are instrumental in natural killer (NK) cell regulation and protect normal tissue from NK cell attack. Human KIR haplotypes comprise genes encoding mainly inhibitory receptors (KIR A) or activating and inhibitory receptors (KIR B). A substantial fraction of humans lack ligands for inhibitory KIRs (iKIRs), i.e. a 'missing ligand' genotype. KIR B/x and missing ligand genotypes may thus give rise to potentially autoreactive, unlicensed NK cells...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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