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https://www.readbyqxmd.com/read/28830460/gene-mutational-pattern-and-expression-level-in-560-acute-myeloid-leukemia-patients-and-their-clinical-relevance
#1
Yong-Mei Zhu, Pan-Pan Wang, Jin-Yan Huang, Yun-Shuo Chen, Bing Chen, Yu-Jun Dai, Han Yan, Yi Hu, Wen-Yan Cheng, Ting-Ting Ma, Sai-Juan Chen, Yang Shen
BACKGROUND: Cytogenetic aberrations and gene mutations have long been regarded as independent prognostic markers in AML, both of which can lead to misexpression of some key genes related to hematopoiesis. It is believed that the expression level of the key genes is associated with the treatment outcome of AML. METHODS: In this study, we analyzed the clinical features and molecular aberrations of 560 newly diagnosed non-M3 AML patients, including mutational status of CEBPA, NPM1, FLT3, C-KIT, NRAS, WT1, DNMT3A, MLL-PTD and IDH1/2, as well as expression levels of MECOM, ERG, GATA2, WT1, BAALC, MEIS1 and SPI1...
August 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28758171/qtl-mapping-for-resistance-to-iridovirus-in-asian-seabass-using-genotyping-by-sequencing
#2
Le Wang, Bin Bai, Shuqing Huang, Peng Liu, Zi Yi Wan, Baoqing Ye, Jinlu Wu, Gen Hua Yue
Identifying quantitative trait loci (QTL) for viral disease resistance is of particular importance in selective breeding programs of fish species. Genetic markers linked to QTL can be useful in marker-assisted selection (MAS) for elites resistant to specific pathogens. Here, we conducted a genome scan for QTL associated with Singapore grouper iridovirus (SGIV) resistance in an Asian seabass (Lates calcarifer) family, using a high-density linkage map generated with genotyping-by-sequencing. One genome-wide significant and three suggestive QTL were detected at LG21, LG6, LG13, and LG15, respectively...
July 31, 2017: Marine Biotechnology
https://www.readbyqxmd.com/read/28749961/prediction-of-novel-target-genes-and-pathways-involved-in-irinotecan-resistant-colorectal-cancer
#3
Precious Takondwa Makondi, Chi-Ming Chu, Po-Li Wei, Yu-Jia Chang
BACKGROUND: Acquired drug resistance to the chemotherapeutic drug irinotecan (the active metabolite of which is SN-38) is one of the significant obstacles in the treatment of advanced colorectal cancer (CRC). The molecular mechanism or targets mediating irinotecan resistance are still unclear. It is urgent to find the irinotecan response biomarkers to improve CRC patients' therapy. METHODS: Genetic Omnibus Database GSE42387 which contained the gene expression profiles of parental and irinotecan-resistant HCT-116 cell lines was used...
2017: PloS One
https://www.readbyqxmd.com/read/28747560/germline-variations-at-jak2-tert-hbs1l-myb-and-mecom-and-the-risk-of-myeloproliferative-neoplasms-in-taiwanese-population
#4
Yi-Hao Chiang, Yu-Cheng Chang, Huan-Chau Lin, Ling Huang, Chun-Chia Cheng, Wei-Ting Wang, Hung-I Cheng, Nai-Wen Su, Caleb Gon-Shen Chen, Johnson Lin, Yi-Fang Chang, Ming-Chih Chang, Ruey-Kuen Hsieh, Wen-Chien Chou, Ken-Hong Lim, Yuan-Yeh Kuo
Germline variations at JAK2, TERT, HBS1L-MYB and MECOM have been found to associate with myeloproliferative neoplasms (MPNs) in European populations. Whether these germline variations are associated with MPNs in Taiwanese population is obscure. Here we aimed to evaluate the association of five germline variations (JAK2 46/1 haplotype tagged by rs12343867, JAK2 intron 8 rs12339666, TERT rs2736100, HBS1L-MYB rs9376092 and MECOM rs2201862) and the risk of MPNs in Taiwanese population. A total of 178 MPN patients (109 essential thrombocythemia, 54 polycythemia vera and 15 primary myelofibrosis) were enrolled into this study...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28710806/clinical-features-and-prognostic-impact-of-prdm16-expression-in-adult-acute-myeloid-leukemia
#5
Genki Yamato, Hiroki Yamaguchi, Hiroshi Handa, Norio Shiba, Machiko Kawamura, Satoshi Wakita, Koiti Inokuchi, Yusuke Hara, Kentaro Ohki, Jun Okubo, Myoung-Ja Park, Manabu Sotomatsu, Hirokazu Arakawa, Yasuhide Hayashi
High PRDM16 (also known as MEL1) expression is a representative marker of acute myeloid leukemia (AML) with NUP98-NSD1 and is a significant predictive marker for poor prognosis in pediatric AML. However, the clinical features of adult AML with PRDM16 expression remain unclear. PRDM16 is highly homologous to MDS1/EVI1, which is an alternatively spliced transcript of MECOM (also known as EVI1). We investigated PRDM16 expression in 151 AML patients, with 47 (31%) exhibiting high PRDM16 expression (PRDM16/ABL1 ratio ≥ 0...
July 14, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28693140/acute-myeloid-leukemia-with-t-3-21-q26-2-q22-developing-following-low-dose-methotrexate-therapy-for-rheumatoid-arthritis-and-expressing-two-aml1-mds1-evi1-fusion-proteins-a-case-report
#6
Keisuke Tanaka, Gaku Oshikawa, Hiroki Akiyama, Shinya Ishida, Toshikage Nagao, Masahide Yamamoto, Osamu Miura
The t(3;21)(q26.2;q22) translocation is a rare chromosomal abnormality exhibited almost exclusively in therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) or in the blastic crisis phase of chronic myelogenous leukemia, which results in the fusion of the runt related transcription factor 1 (RUNX1, also called AML1) gene at 21q22 to the myelodysplasia syndrome 1 (MDS1)-ecotropic virus integration site 1 (EVI1) complex locus (MECOM) at 3q26.2, generating various fusion transcripts, including AML1/MDS1/EVI1 (AME)...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28459701/mecom-evi1-rearrangements-a-review-and-case-report-of-two-mds-patients-with-complex-3q-inversion-deletions
#7
Helen Lawce, Elina Szabo, Yumi Torimaru, Craig Davis, Karin Osterberg, Susan Olson, Steve Moore
Acute myelogeneous leukemia (AML) with inv(3)/t(3;3)(q13q25) is associated with aberrant expression of the stem-cell regulator MECOM (aka EVI1). Two bone marrow samples received in the OHSU Knight Diagnostic Laboratories (KDL) Cytogenetics Laboratory for chromosomes and FISH for a question of progression of myelodysplastic syndrome (MDS) to AML showed complex abnormalities including a deletion of chromosome 3q, one with del(3)(q13q25) and the other with del(3)(q22q25). In light of the prognostic importance of the activation of the MECOM oncogene and the concurrent inactivation of the GATA2 tumor suppressor that occurs with the classic inversion of chromosome 3q, fluorescence in situ hybridization (FISH) was performed using two different probe designs to better define the 3q deletions in the two cases...
2017: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/28409341/zebrafish-pronephros-development
#8
REVIEW
Richard W Naylor, Sarah S Qubisi, Alan J Davidson
The pronephros is the first kidney type to form in vertebrate embryos. The first step of pronephrogenesis in the zebrafish is the formation of the intermediate mesoderm during gastrulation, which occurs in response to secreted morphogens such as BMPs and Nodals. Patterning of the intermediate mesoderm into proximal and distal cell fates is induced by retinoic acid signaling with downstream transcription factors including wt1a, pax2a, pax8, hnf1b, sim1a, mecom, and irx3b. In the anterior intermediate mesoderm, progenitors of the glomerular blood filter migrate and fuse at the midline and recruit a blood supply...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28392805/cadherins-associate-with-distinct-stem-cell-related-transcription-factors-to-coordinate-the-maintenance-of-stemness-in-triple-negative-breast-cancer
#9
Chuanwei Yang, Xuemei Zhao, Naipeng Cui, Yulong Liang
Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with poor prognosis and is enriched in cancer stem cells (CSCs). However, it is not completely understood how the CSCs were maintained in TNBC. In this study, by analyzing The Cancer Genome Atlas (TCGA) provisional datasets and several small-size breast datasets, we found that cadherins (CDHs) 2, 4, 6, and 17 were frequently amplified/overexpressed in 47% of TNBC while E-cadherin (CDH1) was downregulated/mutated at 10%. The alterations of CDH2/4/6/17 were strongly associated with the elevated levels of several stem cell-related transcription factors (SC-TFs) including FOXM1, MCM2, WWTR1, SNAI1, and SOX9...
2017: Stem Cells International
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...
June 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28351939/cytoreductive-conditioning-intensity-predicts-clonal-diversity-in-ada-scid-retroviral-gene-therapy-patients
#11
Aaron R Cooper, Georgia R Lill, Kit Shaw, Denise A Carbonaro-Sarracino, Alejandra Davila, Robert Sokolic, Fabio Candotti, Matteo Pellegrini, Donald B Kohn
Retroviral gene therapy has proved efficacious for multiple genetic diseases of the hematopoietic system, but roughly half of clinical gene therapy trial protocols using gammaretroviral vectors have reported leukemias in some of the patients treated. In dramatic contrast, 39 adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) patients have been treated with 4 distinct gammaretroviral vectors without oncogenic consequence. We investigated clonal dynamics and diversity in a cohort of 15 ADA-SCID children treated with gammaretroviral vectors and found clear evidence of genotoxicity, indicated by numerous common integration sites near proto-oncogenes and by increased abundance of clones with integrations near MECOM and LMO2 These clones showed stable behavior over multiple years and never expanded to the point of dominance or dysplasia...
May 11, 2017: Blood
https://www.readbyqxmd.com/read/28191887/the-creatine-kinase-pathway-is-a-metabolic-vulnerability-in-evi1-positive-acute-myeloid-leukemia
#12
Nina Fenouille, Christopher F Bassil, Issam Ben-Sahra, Lina Benajiba, Gabriela Alexe, Azucena Ramos, Yana Pikman, Amy S Conway, Michael R Burgess, Qing Li, Frédéric Luciano, Patrick Auberger, Ilene Galinsky, Daniel J DeAngelo, Richard M Stone, Yi Zhang, Archibald S Perkins, Kevin Shannon, Michael T Hemann, Alexandre Puissant, Kimberly Stegmaier
Expression of the MECOM (also known as EVI1) proto-oncogene is deregulated by chromosomal translocations in some cases of acute myeloid leukemia (AML) and is associated with poor clinical outcome. Here, through transcriptomic and metabolomic profiling of hematopoietic cells, we reveal that EVI1 overexpression alters cellular metabolism. A screen using pooled short hairpin RNAs (shRNAs) identified the ATP-buffering, mitochondrial creatine kinase CKMT1 as necessary for survival of EVI1-expressing cells in subjects with EVI1-positive AML...
March 2017: Nature Medicine
https://www.readbyqxmd.com/read/28114305/targeted-sequencing-of-lung-function-loci-in-chronic-obstructive-pulmonary-disease-cases-and-controls
#13
María Soler Artigas, Louise V Wain, Nick Shrine, Tricia M McKeever, Ian Sayers, Ian P Hall, Martin D Tobin
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; smoking is the main risk factor for COPD, but genetic factors are also relevant contributors. Genome-wide association studies (GWAS) of the lung function measures used in the diagnosis of COPD have identified a number of loci, however association signals are often broad and collectively these loci only explain a small proportion of the heritability. In order to examine the association with COPD risk of genetic variants down to low allele frequencies, to aid fine-mapping of association signals and to explain more of the missing heritability, we undertook a targeted sequencing study in 300 COPD cases and 300 smoking controls for 26 loci previously reported to be associated with lung function...
2017: PloS One
https://www.readbyqxmd.com/read/27784745/mutational-landscape-and-gene-expression-patterns-in-adult-acute-myeloid-leukemias-with-monosomy-7-as-a-sole-abnormality
#14
Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrózek, Stefano Volinia, James S Blachly, Deedra Nicolet, Christopher Oakes, Karl Kroll, Shelley Orwick, Andrew J Carroll, Richard M Stone, John C Byrd, Albert de la Chapelle, Clara D Bloomfield
Monosomy of chromosome 7 is the most frequent autosomal monosomy in acute myeloid leukemia (AML), where it associates with poor clinical outcomes. However, molecular features associated with this sole monosomy subtype (-7 AML), which may give insights into the basis for its poor prognosis, have not been characterized. In this study, we analyzed 36 cases of -7 AML for mutations in 81 leukemia/cancer-associated genes using a customized targeted next-generation sequencing panel (Miseq). Global gene and miRNA expression profiles were also determined using paired RNA and small RNA sequencing data...
January 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/27620344/intratumoral-heterogeneity-of-frameshift-mutations-in-mecom-gene-is-frequent-in-colorectal-cancers-with-high-microsatellite-instability
#15
Eun Ji Choi, Min Sung Kim, Sang Yong Song, Nam Jin Yoo, Sug Hyung Lee
MECOM gene, also known as EVI, encodes a transcriptional regulator involved in hematopoiesis, apoptosis, development and proliferation. In blood system, MECOM is considered an oncogene, but in solid tumors it has both oncogenic and tumor suppressor activities. Low frequent somatic mutations of MECOM have been detected in many cancers including colorectal cancers (CRC), but the mutation status with respect to the microsatellite instability (MSI) has not been studied. There is an A7 mononucleotide repeat in MECOM coding sequences that could be a mutation target in the cancers with MSI...
January 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27617961/the-pu-1-modulated-microrna-22-is-a-regulator-of-monocyte-macrophage-differentiation-and-acute-myeloid-leukemia
#16
Chao Shen, Ming-Tai Chen, Xin-Hua Zhang, Xiao-Lin Yin, Hong-Mei Ning, Rui Su, Hai-Shuang Lin, Li Song, Fang Wang, Yan-Ni Ma, Hua-Lu Zhao, Jia Yu, Jun-Wu Zhang
MicroRNA-22 (miR-22) is emerging as a critical regulator in organ development and various cancers. However, its role in normal hematopoiesis and leukaemogenesis remains unclear. Here, we detected its increased expression during monocyte/macrophage differentiation of HL-60, THP1 cells and CD34+ hematopoietic stem/progenitor cells, and confirmed that PU.1, a key transcriptional factor for monocyte/macrophage differentiation, is responsible for transcriptional activation of miR-22 during the differentiation. By gain- and loss-of-function experiments, we demonstrated that miR-22 promoted monocyte/macrophage differentiation, and MECOM (EVI1) mRNA is a direct target of miR-22 and MECOM (EVI1) functions as a negative regulator in the differentiation...
September 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27500495/brpf1-is-essential-for-development-of-fetal-hematopoietic-stem-cells
#17
Linya You, Lin Li, Jinfeng Zou, Kezhi Yan, Jad Belle, Anastasia Nijnik, Edwin Wang, Xiang-Jiao Yang
Hematopoietic stem cells (HSCs) serve as a life-long reservoir for all blood cell types and are clinically useful for a variety of HSC transplantation-based therapies. Understanding the role of chromatin organization and regulation in HSC homeostasis may provide important insights into HSC development. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multivalent chromatin regulator that possesses 4 nucleosome-binding domains and activates 3 lysine acetyltransferases (KAT6A, KAT6B, and KAT7), suggesting that this protein has the potential to stimulate crosstalk between different chromatin modifications...
September 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27453784/pediatric-chronic-myeloid-leukemia-with-inv-3-q21q26-2-and-t-lymphoblastic-transformation-a-case-report
#18
Margaret Lewen, Renee Gresh, Maria Queenan, Michele Paessler, Vinodh Pillai, Elizabeth Hexner, Dale Frank, Adam Bagg, Richard Aplenc, Emi Caywood, Gerald Wertheim
BACKGROUND: Chronic myeloid leukemia (CML) comprises ~3 % of pediatric leukemia. Although therapy with tyrosine kinase inhibitors (TKIs) is highly effective for CML, multiple factors have been identified as predictive of treatment failure. Chromosomal abnormalities involving the MECOM locus at 3q26 portend therapy resistant disease in adults, yet have never been described in pediatric patients and have not been associated with T lymphoblastic progression. CASE PRESENTATION: We present a case of an 11-year-old boy with CML possessing the unique combination of T lymphoblastic transformation and a subclone harboring inv(3)(q21q26...
2016: Biomarker Research
https://www.readbyqxmd.com/read/27438527/molecular-basis-of-inherited-thrombocytopenias-an-update
#19
Anna Savoia
PURPOSE OF REVIEW: Inherited thrombocytopenias are a heterogeneous group of diseases caused by mutations in many genes. They account for approximately only 50% of cases, suggesting that novel genes have yet to be identified for a comprehensive understanding of platelet biogenesis defects. This review provides an update of the last year of discoveries on inherited thrombocytopenias focusing on the molecular basis and potential pathogenic mechanisms affecting megakaryopoiesis and platelet production...
September 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/26935937/persistent-polyclonal-binucleated-b-cell-lymphocytosis-and-mecom-gene-amplification
#20
Edouard Cornet, Hossein Mossafa, Karine Courel, Jean-François Lesesve, Xavier Troussard
BACKGROUND: Persistent Polyclonal Binucleated B-cell Lymphocytosis (PPBL) is characterized by a chronic polyclonal B-cell lymphocytosis with binucleated lymphocytes and a polyclonal increase in serum immunoglobulin-M. Cytogenetic is characterized by the presence of a supernumerary isochromosome +i(3)(q10), premature chromosome condensation and chromosomal instability. Outcome of PPBL patients is mostly benign, but subsequent malignancies could occur. The aim of our study is to provide an update of clinical and cytogenetic characteristics of our large cohort of PPBL patients, to describe subsequent malignancies occurring during the follow-up, and to investigate the role of the long arm of chromosome 3 in PPBL...
March 2, 2016: BMC Research Notes
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