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https://www.readbyqxmd.com/read/28210005/mll-is-essential-for-nup98-hoxa9-induced-leukemia
#1
Y Shima, M Yumoto, T Katsumoto, I Kitabayashi
Rearrangements involving the NUP98 gene resulting in fusions to several partner genes occur in acute myeloid leukemia and myelodysplastic syndromes. This study demonstrates that the second FG repeat domain of the NUP98 moiety of the NUP98-HOXA9 fusion protein is important for its cell immortalization and leukemogenesis activities. We demonstrate that NUP98-HOXA9 interacts with MLL via this FG repeat domain and that, in the absence of MLL, NUP98-HOXA9-induced cell immortalization and leukemogenesis are severely inhibited...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28202522/histone-acetyltransferase-activity-of-mof-is-required-for-mll-af9-leukemogenesis
#2
Daria G Valerio, Haiming Xu, Chun-Wei Chen, Takayuki Hoshii, Meghan E Eisold, Christopher Delaney, Monica Cusan, Aniruddha J Deshpande, Chun-Hao Huang, Amaia Lujambio, Y George G Zheng, Johannes Zuber, Tej K Pandita, Scott W Lowe, Scott A Armstrong
Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be a potent suppressor of leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9-driven leukemogenesis reduced tumor burden and prolonged host survival...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28193998/inhibition-of-serotonin-receptor-type-1-in-acute-myeloid-leukemia-impairs-leukemia-stem-cell-functionality-a-promising-novel-therapeutic-target
#3
A Etxabe, M C Lara-Castillo, J M Cornet-Masana, A Banús-Mulet, M Nomdedeu, M A Torrente, M Pratcorona, M Díaz-Beyá, J Esteve, R M Risueño
Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous neoplasia with poor outcome, organized as a hierarchy initiated and maintained by a subpopulation with differentiation and self-renewal capacities called leukemia stem cells (LSCs). Although currently used chemotherapy is capable of initially reducing the tumor burden producing a complete remission, most patients will ultimately relapse and will succumb to their disease. As such, new therapeutic strategies are needed. AML cells differentially expressed serotonin receptors type 1 (HTR1) compared to healthy blood cells and the most primitive hematopoietic fraction; in fact, HTR1B expression on AML patient samples correlated with clinical outcome...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28183848/long-term-observation-reveals-high-frequency-engraftment-of-human-acute-myeloid-leukemia-in-immunodeficient-mice
#4
Anna M Paczulla, Stephan Dirnhofer, Martina Konantz, Michael Medinger, Helmut R Salih, Kathrin Rothfelder, Dimitrios A Tsakiris, Jakob R Passweg, Pontus Lundberg, Claudia Lengerke
Repopulation of immunodeficient mice remains the primary method to func-tionally assess human acute myeloid leukemia. Published data report en-graftment of ~40-66% of cases, mostly belonging to intermediate or poor risk subtypes. Here we report that extending follow-up beyond the standard analysis end-points of 10 to 16 weeks post-transplantation permitted leukemic engraftment from nearly every xenotransplanted acute myeloid leukemia case (18/19, ~95%). Xenogeneic leukemic cells showed conserved immune phenotypes and genetic signatures when compared to corresponding pre-transplant cells, and were furthermore able to induce leukemia in re-transplantation assays...
February 9, 2017: Haematologica
https://www.readbyqxmd.com/read/28179318/rearrangement-of-the-chromatin-organizer-special-at-rich-binding-protein-1-gene-satb1-resulting-from-a-t-3-5-p24-q14-chromosomal-translocation-in-acute-myeloid-leukemia
#5
Synne Torkildsen, Marta Brunetti, Ludmila Gorunova, Signe Spetalen, Klaus Beiske, Sverre Heim, Ioannis Panagopoulos
BACKGROUND/AIM: New chromosomal aberrations continue to be reported in acute myeloid leukemias (AML). The addition of more cases with the same genetic characteristics would establish an acquired aberration as a recurrent change, help determine its prognostic significance, and can provide insight into the mechanisms of leukemogenesis in patients with these rare abnormalities. CASE REPORT: RNA-sequencing was performed on a patient with AML with the bone marrow karyotype 46,XY,t(3;5)(p24;q14)[5]/46,XY[10]...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28179274/mouse-models-of-mll-leukemia-recapitulating-the-human-disease
#6
Thomas A Milne
Chromosome translocations involving the Mixed Lineage Leukemia (MLL) gene fuse it in frame with multiple partner genes creating novel fusion proteins (MLL-FPs) that cause aggressive acute leukemias in humans. Animal models of human disease are important for the exploration of underlying disease mechanisms as well for testing novel therapeutic approaches. Patients carrying MLL-FPs have very few cooperating mutations, making MLL-FP driven leukemias ideal for animal modeling. This has allowed for a wide range of different experimental model systems designed to explore different aspects of MLL-FP leukemogenesis...
February 8, 2017: Blood
https://www.readbyqxmd.com/read/28176225/regulation-of-normal-and-leukemic-stem-cells-through-cytokine-signaling-and-the-microenvironment
#7
REVIEW
Virginia Camacho, Victoria McClearn, Sweta Patel, Robert S Welner
Leukemias depend on transformed stem cells for their growth and thus these cells represent important therapeutic targets. However, leukemic stem cells resemble normal hematopoietic stem cells (HSCs) with respect to most surface markers, gene expression patterns, and ability to be transplanted. Furthermore, the microenvironment that supports healthy HSCs non-hematopoietic populations, and immune cells correspondingly, the cytokines, adhesion molecules and signal transduction pathways are also impaired during leukemogenesis...
February 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28159735/the-microenvironment-in-human-myeloid-malignancies-emerging-concepts-and-therapeutic-implications
#8
Hind Medyouf
Similar to their healthy counterpart, malignant hematopoietic stem cells in myeloid malignancies such as myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), reside in a highly complex and dynamic cellular microenvironment in the bone marrow. This environment provides key regulatory signals for and tightly controls cardinal features of HSCs, including self-renewal, quiescence, differentiation and migration. These features are essential to maintaining cellular homeostasis and blood regeneration throughout life...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28152414/coexisting-and-cooperating-mutations-in-npm1-mutated-acute-myeloid-leukemia
#9
Jay L Patel, Jonathan A Schumacher, Kimberly Frizzell, Shelly Sorrells, Wei Shen, Adam Clayton, Rakhi Jattani, Todd W Kelley
NPM1 insertion mutations represent a common recurrent genetic abnormality in acute myeloid leukemia (AML) patients. The frequency of these mutations varies from approximately 30% overall up to 50% in patients with a normal karyotype. Several recent studies have exploited advances in massively parallel sequencing technology to shed light on the complex genomic landscape of AML. We hypothesize that variant allele fraction (VAF) data derived from massively parallel sequencing studies may provide further insights into the clonal architecture and pathogenesis of NPM1-driven leukemogenesis...
January 23, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28143869/stabilization-of-notch1-by-the-hsp90-chaperon-is-crucial-for-t-cell-leukemogenesis
#10
Zhaojing Wang, Yufeng Hu, Daibiao Xiao, Jingchao Wang, Chuntao Liu, Yisheng Xu, Xiaomeng Shi, Peng Jiang, Liang Huang, Peng Li, Hudan Liu, Guoliang Qing
PURPOSE: Notch1 deregulation is assuming a focal role in T-cell acute lymphoblastic leukemia (T-ALL). Despite tremendous advances in our understanding of Notch1 transcriptional programs, the mechanisms by which Notch1 stability and turnover are regulated remain obscure. The goal of the present study is to identify intracellular Notch1 (ICN1, the activated form of Notch1) binding partner(s) regulating its stability and activity. EXPERIMENTAL DESIGN: We employed immunoaffinity purification to identify ICN1-associating partner and used co-immunoprecipitation to verify the endogenous protein interaction...
January 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28142295/identification-of-a-tumor-suppressor-network-in-t-cell-leukemia
#11
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Maren Kaufmann, Roderick A F MacLeod, Hans G Drexler
To identify novel cancer-related genes targeted by copy number alterations, we performed genomic profiling of T-cell acute lymphoblastic leukemia (T-ALL) cell lines. In 3/8, we identified a shared deletion at chromosomal position 2p16.3-p21. Within the minimally deleted region, we recognized several candidate tumor suppressor (TS) genes, including FBXO11 and FOXN2. An additional deletion at chromosome 14q23.2-q32.11 included FOXN3, highlighting this class of FOX genes as potential TS. Quantitative expression analyses of FBXO11, FOXN2, and FOXN3 confirmed reduced transcript levels in the identified cell lines...
January 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28130996/association-of-maternal-and-index-child-s-diet-with-subsequent-leukemia-risk-a-systematic-review-and-meta-analysis
#12
REVIEW
Nick Dessypris, Maria A Karalexi, Evangelos Ntouvelis, Andreas-Antonios Diamantaras, Vassilios Papadakis, Margarita Baka, Emmanuel Hatzipantelis, Maria Kourti, Maria Moschovi, Sophia Polychronopoulou, Vasiliki Sidi, Eftichia Stiakaki, Eleni Th Petridou
BACKGROUND: Exploring the effect of maternal and/or childhood diet on offspring leukemogenesis is challenging, given differences in food group categories, their potentially variable impact depending on time window of exposure and the multiple leukemia subtypes. We opted to quantitatively synthesize published data on the association of maternal/child diet with leukemia risk. METHODS: Medline was searched until June 30th, 2016 for eligible articles on the association of childhood leukemia with consumption of (i) food groups, excluding alcoholic and non-alcoholic beverages, and (ii) specific dietary supplements before/during index pregnancy and childhood...
January 25, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28126968/cd244-maintains-the-proliferation-ability-of-leukemia-initiating-cells-through-shp-2-p27kip1-signaling
#13
Feifei Zhang, Xiaoye Liu, Chiqi Chen, Jun Zhu, Zhuo Yu, Jingjing Xie, Li Xie, Haitao Bai, Yaping Zhang, Xia Fang, Hao Gu, Chun Wang, Wei Weng, Cheng Cheng Zhang, Guo-Qiang Chen, Aibing Liang, Junke Zheng
Targeting leukemia initiating cells is considered to be an effective way to cure leukemia, for which it is critical to identify novel therapeutic targets. Herein, we demonstrate that CD244, which is initially reported as a key regulator for NK cells, is highly expressed on both mouse and human leukemia initiating cells. Upon CD244 knockdown, human leukemia cell lines and primary leukemia cells have markedly impaired proliferation abilities both in vitro and in vivo. Interestingly, the repopulation ability of both mouse and human hematopoietic stem cells is not impaired upon CD244 knockdown...
January 25, 2017: Haematologica
https://www.readbyqxmd.com/read/28115367/lgl-leukemia-from-pathogenesis-to-treatment
#14
Thierry Lamy, Aline Moignet, Thomas P Loughran
Large granular lymphocyte (LGL) leukemia has been recognized by the WHO classifications among mature T cell and NK cell neoplasms. There are 3 categories: chronic T cell leukemia and NK cell lymphocytosis which are similarly indolent diseases characterized by cytopenias and autoimmune conditions as opposed to aggressive NK cell LGL leukemia. Clonal LGL expansion arise from chronic antigenic stimulation which promotes dysregulation of apoptosis, mainly due to constitutive activation of survival pathways including Jak/Stat, MapK, Pi3k-Akt, RasRaf-1, MEK1/ERK, sphingolipid, and NFκB...
January 23, 2017: Blood
https://www.readbyqxmd.com/read/28115366/adult-t-cell-leukemia-atl-molecular-basis-for-clonal-expansion-and-transformation-of-htlv-1-infected-t-cells
#15
Toshiki Watanabe
Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) that develops through a multistep carcinogenesis process involving five or more genetic events. In this review, we provided a comprehensive overview of recently uncovered information on the molecular basis of leukemogenesis in ATL. Broadly, the landscape of genetic abnormalities in ATL that include alterations highly enriched in genes for T cell receptor-NF-κB signaling such as PLCG1, PRKCB, and CARD11 and gain-of function mutations in CCR4 and CCR7 Conversely, the epigenetic landscape of ATL can be summarized as polycomb repressive complex 2 (PRC2) hyperactivation with genome-wide H3K27 me3 accumulation as the basis of the unique transcriptome of ATL cells...
January 23, 2017: Blood
https://www.readbyqxmd.com/read/28111462/biological-and-clinical-consequences-of-npm1-mutations-in-aml
#16
REVIEW
E M Heath, S M Chan, M D Minden, T Murphy, L I Shlush, A D Schimmer
Acute myeloid leukemia (AML) is characterized by accumulation of myeloid cells in the bone marrow because of impaired differentiation and proliferation, resulting in hematopoietic insufficiency. NPM1 is one of the most commonly mutated genes in AML, present in 20-30% of cases. Mutations in NPM1 represent a distinct entity in the World Health Organization (WHO) classification and commonly indicate a better risk prognosis. In this review, we discuss the many functions of NPM1, the consequence of mutations in NPM1 and possible mechanisms through which mutations lead to leukemogenesis...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28103322/htlv-1-tax-induces-formation-of-the-active-macromolecular-ikk-complex-by-generating-lys63-and-met1-linked-hybrid-polyubiquitin-chains
#17
Yuri Shibata, Fuminori Tokunaga, Eiji Goto, Ginga Komatsu, Jin Gohda, Yasushi Saeki, Keiji Tanaka, Hirotaka Takahashi, Tatsuya Sawasaki, Satoshi Inoue, Hiroyuki Oshiumi, Tsukasa Seya, Hiroyasu Nakano, Yuetsu Tanaka, Kazuhiro Iwai, Jun-Ichiro Inoue
The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28101221/a-complex-translocation-3-17-15-in-acute-promyelocytic-leukemia-confirmed-by-fluorescence-in-situ-hybridization
#18
Yanming Wang, Junjie Ma, Xinguang Liu, Riming Liu, Lingling Xu, Li Wang, Jiannong Cen, Xiaoxia Chu
Acute promyelocytic leukemia (APL) is typified by t(15;17)(q22;q21), generating the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid α-receptor (RARA) gene at 17q21. The PML-RARA fusion gene is believed to play a vital role in leukemogenesis. A sizeable minority of patients with complex variants of APL have been reported. The present study reports the case of a 33-year-old male with APL carrying a potential complex translocation. The initial symptom was bleeding gums. Chromosomal analysis of the bone marrow cells revealed an atypical 17q aberration...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28091414/acute-myeloid-leukemia-advancements-in-diagnosis-and-treatment
#19
REVIEW
Meng-Ge Yu, Hu-Yong Zheng
OBJECTIVE: Leukemia is the most common pediatric malignancy and a major cause of morbidity and mortality in children. Among all subtypes, a lack of consensus exists regarding the diagnosis and treatment of acute myeloid leukemia (AML). Patient survival rates have remained modest for the past three decades in AML. Recently, targeted therapy has emerged as a promising treatment. DATA SOURCES: We searched the PubMed database for recently published research papers on diagnostic development, target therapy, and other novel therapies of AML...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28087573/fto-mediated-mrna-demethylation-drives-leukemogenesis
#20
(no author information available yet)
The mRNA demethylase FTO promotes leukemogenesis and inhibits ATRA-mediated differentiation.
January 13, 2017: Cancer Discovery
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