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leukemogenesis

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https://www.readbyqxmd.com/read/28428987/microarray-profiling-and-co-expression-network-analysis-of-the-lncrnas-and-mrnas-associated-with-acute-leukemia-in-adults
#1
Hui Cheng, Chong Mei Huang, Yang Wang, Xiao Xia Hu, Xiao Qian Xu, Xian Min Song, Gu Sheng Tang, Li Chen, Jian Min Yang
Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common types of acute leukemia in adults and cause low survival rate and poor outcome after 5 years despite high rates of complete remission (CR) with modern chemotherapeutic regimens. To understand the distinct mechanisms in leukemogenesis for ALL and AML and to identify markers for diagnosis and treatment, lncRNA and mRNA expression profiles of AML and ALL patients and healthy controls were generated using microarray analysis. For comparison, the differentially expressed mRNA functions were annotated using gene ontology (GO) and pathway analysis...
April 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28423121/telomere-length-analysis-in-monoclonal-b-cell-lymphocytosis-and-chronic-lymphocytic-leukemia-binet-a
#2
F M Furtado, P S Scheucher, B A Santana, N F Scatena, R T Calado, E M Rego, D M Matos, R P Falcão
Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic clinical entity characterized by the proliferation of monoclonal B cells not meeting the diagnosis criteria for chronic lymphocytic leukemia (CLL). MBL may precede the development of CLL, but the molecular mechanisms responsible for disease progression and evolution are not completely known. Telomeres are usually short in CLL and their attrition may contribute to disease evolution. Here, we determined the telomere lengths of CD5+CD19+ cells in MBL, CLL, and healthy volunteers...
April 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28418909/pathogenesis-of-etv6-runx1-positive-childhood-acute-lymphoblastic-leukemia-and-mechanisms-underlying-its-relapse
#3
REVIEW
Congcong Sun, Lixian Chang, Xiaofan Zhu
ETV6/RUNX1 (E/R) is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL). Multiple lines of evidence imply a "two-hit" model for the molecular pathogenesis of E/R-positive ALL, whereby E/R rearrangement is followed by a series of secondary mutations that trigger overt leukemia. The cellular framework in which E/R arises and the maintenance of a pre-leukemic condition by E/R are fundamental to the mechanism that underlies leukemogenesis. Accordingly, a variety of studies have focused on the relationship between the clones giving rise to the primary and recurrent E/R-positive ALL...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416638/eya2-a-target-activated-by-plzf-is-critical-for-plzf-rara-induced-leukemogenesis
#4
Ryoichi Ono, Masahiro Masuya, Satomi Ishii, Naoyuki Katayama, Tetsuya Nosaka
PLZF is a transcription factor that confers aberrant self-renewal in leukemogenesis, and the PLZF-RARA fusion gene causes acute promyelocytic leukemia (APL) through differentiation block. However, the molecular mechanisms of aberrant self-renewal underlying PLZF-mediated leukemogenesis are poorly understood. To investigate these mechanisms, comprehensive expression profiling of mouse hematopoietic stem/progenitor cells transduced with Plzf was performed, which revealed the involvement of a key transcriptional coactivator, Eya2, a target molecule shared by Plzf and PLZF-RARA, in the aberrant self-renewal...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28415626/hematopoietic-stem-progenitor-cells-are-less-prone-to-undergo-apoptosis-than-lymphocytes-despite-similar-dna-damage-response
#5
Matus Durdik, Pavol Kosik, Jana Kruzliakova, Lukas Jakl, Eva Markova, Igor Belyaev
Hematopoietic stem/progenitor CD34+ cells (HSPC) give rise to all types of blood cells and represent a key cellular target for origination of leukemia. Apoptosis and repair of DNA double strand breaks (DSB) are vital processes in leukemogenesis. High doses of ionizing radiation are the best known agent that induces leukemia, but less is known about the leukemogenic potential of low doses. While umbilical cord blood (UCB) serves as a valuable source of the HSPC for both research and clinics, the data on DNA damage response and apoptosis in UCB HSPC are very limited...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415601/regulatory-network-of-gata3-in-pediatric-acute-lymphoblastic-leukemia
#6
Qianqian Hou, Fei Liao, Shouyue Zhang, Duyu Zhang, Yan Zhang, Xueyan Zhou, Xuyang Xia, Yuanxin Ye, Hanshuo Yang, Zhaozhi Li, Leiming Wang, Xi Wang, Zhigui Ma, Yiping Zhu, Liang Ouyang, Yuelan Wang, Hui Zhang, Li Yang, Heng Xu, Yang Shu
GATA3 polymorphisms were reported to be significantly associated with susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism located around in the tissue-specific enhancer, and significantly associated with GATA3 expression. Although the regulatory network of GATA3 has been well reported in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus conducted genome-wide gene expression association analyses to reveal expression associated genes and pathways in nine independent B-ALL patient cohorts...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402264/fhl2-interacts-with-iaspp-and-impacts-the-biological-functions-of-leukemia-cells
#7
Wenting Lu, Tengteng Yu, Shuang Liu, Saisai Li, Shouyun Li, Jia Liu, Yingxi Xu, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Jianxiang Wang, Min Wang
iASPP is an inhibitory member of apoptosis-stimulating proteins of p53 (ASPP) family, which inhibits p53-dependent apoptosis. iASPP was highly expressed in acute leukemia, inhibited leukemia cells apoptosis and promoted leukemogenesis. In order to clarify its mechanism, a yeast two-hybrid screen was performed and FHL2 was identified for the first time as one of the binding proteins of iASPP. FHL2 was highly expressed in K562 and Kasumi-1 cells. FHL2 and iASPP interacted with each other and co-localized in both nucleus and cytoplasm...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400619/dysfunction-of-the-wt1-meg3-signaling-promotes-aml-leukemogenesis-via-p53-dependent-and-independent-pathways
#8
Y Lyu, J Lou, Y Yang, J Feng, Y Hao, S Huang, L Yin, J Xu, D Huang, B Ma, D Zou, Y Wang, Y Zhang, B Zhang, P Chen, K Yu, Ew-F Lam, X Wang, Q Liu, J Yan, B Jin
Long non-coding RNAs (lncRNAs) play a pivotal role in tumorigenesis, exemplified by the recent finding that lncRNA MEG3 inhibits tumor growth in a p53-dependent manner. Acute myeloid leukemia (AML) is the most common malignant myeloid disorder in adults, and TP53 mutations or loss are frequently detected in patients with therapy-related AML or AML with complex karyotype. Here, we reveal that MEG3 is significantly down-regulated in AML and suppresses leukemogenesis in not only a p53-dependent, but also a p53-independent manner...
April 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28399410/hoxa9-and-meis1-cooperatively-induce-addiction-to-syk-signaling-by-suppressing-mir-146a-in-acute-myeloid-leukemia
#9
Sebastian Mohr, Carmen Doebele, Federico Comoglio, Tobias Berg, Julia Beck, Hanibal Bohnenberger, Gabriela Alexe, Jasmin Corso, Philipp Ströbel, Astrid Wachter, Tim Beissbarth, Frank Schnütgen, Anjali Cremer, Nadine Haetscher, Stefanie Göllner, Arefeh Rouhi, Lars Palmqvist, Michael A Rieger, Timm Schroeder, Halvard Bönig, Carsten Müller-Tidow, Florian Kuchenbauer, Ekkehard Schütz, Anthony R Green, Henning Urlaub, Kimberly Stegmaier, R Keith Humphries, Hubert Serve, Thomas Oellerich
The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28391050/the-mds-and-evi1-complex-locus-mecom-isoforms-regulate-their-own-transcription-and-have-different-roles-in-the-transformation-of-hematopoietic-stem-and-progenitor-cells
#10
Miren Maicas, Iria Vázquez, Rafael Alis, Nerea Marcotegui, Leire Urquiza, Xabier Cortés-Lavaud, Ion Cristóbal, María A García-Sánchez, María D Odero
Transcriptional activation of the EVI1 oncogene (3q26) leads to aggressive forms of human acute myeloid leukemia (AML). However, the mechanism of EVI1-mediated leukemogenesis has not been fully elucidated. Previously, by characterizing the EVI1 promoter, we have shown that RUNX1 and ELK1 directly regulate EVI1 transcription. Intriguingly, bioinformatic analysis of the EVI1 promoter region identified the presence of several EVI1 potential binding sites. Thus, we hypothesized that EVI1 could bind to these sites regulating its own transcription...
April 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28381396/caspase-3-controls-aml1-eto-driven-leukemogenesis-via-autophagy-modulation-in-a-ulk1-dependent-manner
#11
Na Man, Yurong Tan, Xiao-Jian Sun, Fan Liu, Guoyan Cheng, Sarah Greenblatt, Camilo Martinez, Daniel L Karl, Koji Ando, Ming Sun, Dan Hou, Bingyi Chen, Mingjiang Xu, Feng-Chun Yang, Zhu Chen, Saijuan Chen, Stephen D Nimer, Lan Wang
AML1-ETO (AE), a fusion oncoprotein, generated by the t(8;21), can trigger acute myeloid leukemia (AML) in collaboration with mutations including c-Kit, ASXL1/2, FLT3, N-RAS, and K-RAS. Caspase-3, a key executor among its family, plays multiple roles in cellular processes, including hematopoietic development and leukemia progression. Caspase-3 was revealed to directly cleave AE in vitro, suggesting that AE may accumulate in a Caspase-3 compromised background and thereby accelerate leukemogenesis. Therefore, we developed a Caspase-3 knockout genetic mouse model of AML and found that loss of Caspase-3 actually delayed AML1-ETO9a (AE9a)-driven leukemogenesis, indicating that Caspase-3 may play distinct roles in the initiation and/or progression of AML...
April 5, 2017: Blood
https://www.readbyqxmd.com/read/28379884/parental-alcohol-consumption-and-risk-of-leukemia-in-the-offspring-a-systematic-review-and-meta-analysis
#12
Maria A Karalexi, Nick Dessypris, Thomas P Thomopoulos, Evangelos Ntouvelis, Maria Kantzanou, Andreas-Antonios Diamantaras, Maria Moschovi, Margarita Baka, Emmanuel Hatzipantelis, Maria Kourti, Sophia Polychronopoulou, Eftichia Stiakaki, Ana-M Mora, Victor Wunsch-Filho, Claire Infante-Rivard, Dimitrios Loutradis, Eleni Th Petridou
Parental alcohol consumption before and during pregnancy has been linked to adverse outcomes in the offspring including leukemogenesis. We, therefore, aimed to systematically assess and quantitatively synthesize published data on the association of paternal consumption during preconception and maternal consumption during pregnancy with leukemia risk in childhood (0-14 years). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed (until February 2016) and the reference lists of the relevant studies...
April 4, 2017: European Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28375557/genome-wide-association-study-on-monoclonal-gammopathy-of-unknown-significance-mgus
#13
Hauke Thomsen, Chiara Campo, Niels Weinhold, Miguel Inacio da Silva Filho, Luděk Pour, Evžen Gregora, Pavel Vodicka, Ludmila Vodickova, Per Hoffmann, Markus M Nöthen, Karl-Heinz Jöckel, Christian Langer, Roman Hajek, Hartmut Goldschmidt, Kari Hemminki, Asta Försti
OBJECTIVES: To identify germline variants contributing to the development of monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic pre-malignant precursor for multiple myeloma (MM). METHODS: We conducted the first genome-wide association study (GWAS) on MGUS on 243 German cases with a replication on 294 Czech cases. Identified loci were further analyzed in 1508 German MM patients. New MM loci recently reported in a meta-analysis were also tested in the MGUS GWAS...
April 4, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28367807/-autophagy-a-key-player-in-leukemogenesis-and-a-therapeutic-target-in-hematopoietic-malignancies
#14
Arnaud Jacquel, Frédéric Luciano, Alexandre Puissant, Guillaume Robert, Patrick Auberger
No abstract text is available yet for this article.
March 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28361856/aberrant-promoter-hypermethylation-of-selected-apoptotic-genes-in-childhood-acute-lymphoblastic-leukemia-among-north-indian-population
#15
M Nikbakht, A K Jha, K Malekzadeh, M Askari, S Mohammadi, R K Marwaha, D Kaul, J Kaur
Promoter hypermethylation mediates gene silencing in many neoplasms. Acute leukemia has been reported to harbor multiple genes aberrantly silenced by hypermethylation. AIM: In present study, we investigated the prevalence of hypermethylation of caspase-8 (CASP8), TMS1 and DAPK genes in correlation with clinicopathological factors in childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A case-control study has been conducted based on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls...
March 2017: Experimental Oncology
https://www.readbyqxmd.com/read/28360416/heterodimerization-of-aml1-eto-with-cbf%C3%AE-is-required-for-leukemogenesis-but-not-for-myeloproliferation
#16
V Thiel, B D Giaimo, P Schwarz, K Soller, V Vas, M Bartkuhn, T J Blätte, K Döhner, L Bullinger, T Borggrefe, H Geiger, F Oswald
The AML1/Runx1 transcription factor and its heterodimerization partner CBFβ are essential regulators of myeloid differentiation. The chromosomal translocation t(8;21), fusing the DNA binding domain of AML1 to the corepressor eight-twenty-one (ETO), is frequently associated with acute myeloid leukemia (AML) and generates the AML1/ETO (AE) fusion protein. AE represses target genes usually activated by AML1 and also affects the endogenous repressive function of ETO at Notch target genes. In order to analyze the contribution of CBFβ in AE-mediated leukemogenesis and deregulation of Notch target genes, we introduced two point mutations in a leukemia initiating version of AE in mice, called AE9a, that disrupt the AML1/CBFβ interaction (AE9aNT)...
March 31, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28351936/endoglin-a-novel-target-for-therapeutic-intervention-in-acute-leukemias-revealed-in-xenograft-mouse-models
#17
Keina M C Dourado, June Baik, Vanessa K P Oliveira, Miriam Beltrame, Ami Yamamoto, Charles P Theuer, Camila A V Figueiredo, Michael R Verneris, Rita C R Perlingeiro
Endoglin (CD105), a receptor of the transforming growth factor-β (TGF-β) superfamily, has been reported to identify functional long-term repopulating hematopoietic stem cells, and has been detected in certain sub-types of acute leukemias. Whether this receptor plays a functional role in leukemogenesis remains unknown. We identified endoglin expression on the majority of blasts from patients with acute myeloid leukemia (AML) and acute B-lymphoblastic leukemia (B-ALL). Using a xenograft model, we find that CD105(+) blasts are endowed with superior leukemogenic activity compared to the CD105(-) population...
March 28, 2017: Blood
https://www.readbyqxmd.com/read/28334174/dna-damage-response-in-hematopoietic-stem-cells-an-evolutionary-trade-off-between-blood-regeneration-and-leukemia-suppression
#18
Shahar Biechonski, Muhammad Yassin, Michael Milyavsky
Self-renewing and multipotent hematopoietic stem cells (HSCs) maintain lifelong hematopoiesis. Their enormous regenerative potential coupled with lifetime persistence in the body, in contrast with the Progenitors, demand tight control of HSCs genome stability. Indeed, failure to accurately repair DNA damage in HSCs is associated with bone marrow failure and accelerated leukemogenesis. Recent observations exposed remarkable differences in several DNA-damage response (DDR) aspects between HSCs and Progenitors, especially in their DNA-repair capacities and susceptibility to apoptosis...
April 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28314854/common-nonmutational-notch1-activation-in-chronic-lymphocytic-leukemia
#19
Giulia Fabbri, Antony B Holmes, Mara Viganotti, Claudio Scuoppo, Laura Belver, Daniel Herranz, Xiao-Jie Yan, Yasmine Kieso, Davide Rossi, Gianluca Gaidano, Nicholas Chiorazzi, Adolfo A Ferrando, Riccardo Dalla-Favera
Activating mutations of NOTCH1 (a well-known oncogene in T-cell acute lymphoblastic leukemia) are present in ∼4-13% of chronic lymphocytic leukemia (CLL) cases, where they are associated with disease progression and chemorefractoriness. However, the specific role of NOTCH1 in leukemogenesis remains to be established. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ∼50% of peripheral blood CLL cases lacking gene mutations. We identify a "NOTCH1 gene-expression signature" in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28314168/mir-137-downregulates-c-kit-expression-in-acute-myeloid-leukemia
#20
Yanping Hu, Xiaolong Dong, Guoming Chu, Guangrui Lai, Bijun Zhang, Leitong Wang, Yanyan Zhao
The oncogene c-kit plays a vital role in the pathogenesis of acute myeloid leukemia (AML). However, the mechanism of microRNAs targeting c-kit in AML has not been determined in detail. Moreover, the role miR-137 in tumor cell proliferation remains controversial. The aim of this work was to verify whether miR-137 targets c-kit and to research the biological effects of restoring miR-137 expression in leukemia cells. We found that miR-137 binds specifically to the 3'-UTR of c-kit and suppresses the expression and activities of c-kit...
February 16, 2017: Leukemia Research
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