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leukemia genomic

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https://www.readbyqxmd.com/read/29241165/sc1-promotes-mir124-3p-expression-to-maintain-the-self-renewal-of-mouse-embryonic-stem-cells-by-inhibiting-the-mek-erk-pathway
#1
Qing Wei, Hongliang Liu, Zhiying Ai, Yongyan Wu, Yingxiang Liu, Zhaopeng Shi, Xuexue Ren, Zekun Guo
BACKGROUND/AIMS: Self-renewal is one of the most important features of embryonic stem (ES) cells. SC1 is a small molecule modulator that effectively maintains the self-renewal of mouse ES cells in the absence of leukemia inhibitory factor (LIF), serum and feeder cells. However, the mechanism by which SC1 maintains the undifferentiated state of mouse ES cells remains unclear. METHODS: In this study, microarray and small RNA deep-sequencing experiments were performed on mouse ES cells treated with or without SC1 to identify the key genes and microRNAs that contributed to self-renewal...
December 12, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29238226/maternal-diabetes-and-incidence-of-childhood-cancer-a-nationwide-cohort-study-and-exploratory-genetic-analysis
#2
Anna Deleskog, Marcel den Hoed, Giorgio Tettamanti, Sofia Carlsson, Rickard Ljung, Maria Feychting, Hannah L Brooke
Background: The etiology of childhood cancer is not well understood, but may be linked to prenatal and perinatal factors, such as maternal diabetes. However, this association has not been examined in depth. We aimed to determine if maternal diabetes is associated with risk of childhood brain tumor (CBT), leukemia (all types combined and acute lymphoblastic leukemia [ALL] separately), and lymphoma. Methods: All children born in Sweden between 1973 and 2014 (n=4,239,965) were followed from birth until first cancer diagnosis, age 15 years, or December 31, 2015...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/29236701/anti-leukemic-activity-of-bortezomib-and-carfilzomib-on-b-cell-precursor-all-cell-lines
#3
Kazuya Takahashi, Takeshi Inukai, Toshihiko Imamura, Mio Yano, Chihiro Tomoyasu, David M Lucas, Atsushi Nemoto, Hiroki Sato, Meixian Huang, Masako Abe, Keiko Kagami, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Koshi Akahane, Kumiko Goi, Jiro Kikuchi, Yusuke Furukawa, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Kanji Sugita
Prognosis of childhood acute lymphoblastic leukemia (ALL) has been dramatically improved. However, prognosis of the cases refractory to primary therapy is still poor. Recent phase 2 study on the efficacy of combination chemotherapy with bortezomib (BTZ), a proteasome inhibitor, for refractory childhood ALL demonstrated favorable clinical outcomes. However, septic death was observed in over 10% of patients, indicating the necessity of biomarkers that could predict BTZ sensitivity. We investigated in vitro BTZ sensitivity in a large panel of ALL cell lines that acted as a model system for refractory ALL, and found that Philadelphia chromosome-positive (Ph+) ALL, IKZF1 deletion, and biallelic loss of CDKN2A were associated with favorable response...
2017: PloS One
https://www.readbyqxmd.com/read/29229977/proteomic-and-genomic-integration-identifies-kinase-and-differentiation-determinants-of-kinase-inhibitor-sensitivity-in-leukemia-cells
#4
P Casado, E H Wilkes, F Miraki-Moud, M M Hadi, A Rio-Machin, V Rajeeve, R Pike, S Iqbal, S Marfa, N Lea, S Best, J Gribben, J Fitzgibbon, P R Cutillas
Leukemia accepted article preview online, 12 December 2017. doi:10.1038/leu.2017.349.
December 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29227476/the-molecular-landscape-of-pediatric-acute-myeloid-leukemia-reveals-recurrent-structural-alterations-and-age-specific-mutational-interactions
#5
Hamid Bolouri, Jason E Farrar, Timothy Triche, Rhonda E Ries, Emilia L Lim, Todd A Alonzo, Yussanne Ma, Richard Moore, Andrew J Mungall, Marco A Marra, Jinghui Zhang, Xiaotu Ma, Yu Liu, Yanling Liu, Jaime M Guidry Auvil, Tanja M Davidsen, Patee Gesuwan, Leandro C Hermida, Bodour Salhia, Stephen Capone, Giridharan Ramsingh, Christian Michel Zwaan, Sanne Noort, Stephen R Piccolo, E Anders Kolb, Alan S Gamis, Malcolm A Smith, Daniela S Gerhard, Soheil Meshinchi
We present the molecular landscape of pediatric acute myeloid leukemia (AML) and characterize nearly 1,000 participants in Children's Oncology Group (COG) AML trials. The COG-National Cancer Institute (NCI) TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA and microRNA sequencing and CpG methylation profiling. Validated DNA variants corresponded to diverse, infrequent mutations, with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including new gene fusions and focal deletions of MBNL1, ZEB2 and ELF1, were disproportionately prevalent in young individuals as compared to adults...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29227286/drug-perturbation-based-stratification-of-blood-cancer
#6
Sascha Dietrich, Małgorzata Oleś, Junyan Lu, Leopold Sellner, Simon Anders, Britta Velten, Bian Wu, Jennifer Hüllein, Michelle da Silva Liberio, Tatjana Walther, Lena Wagner, Sophie Rabe, Sonja Ghidelli-Disse, Marcus Bantscheff, Andrzej K Oleś, Mikołaj Słabicki, Andreas Mock, Christopher C Oakes, Shihui Wang, Sina Oppermann, Marina Lukas, Vladislav Kim, Martin Sill, Axel Benner, Anna Jauch, Lesley Ann Sutton, Emma Young, Richard Rosenquist, Xiyang Liu, Alexander Jethwa, Kwang Seok Lee, Joe Lewis, Kerstin Putzker, Christoph Lutz, Davide Rossi, Andriy Mokhir, Thomas Oellerich, Katja Zirlik, Marco Herling, Florence Nguyen-Khac, Christoph Plass, Emma Andersson, Satu Mustjoki, Christof von Kalle, Anthony D Ho, Manfred Hensel, Jan Dürig, Ingo Ringshausen, Marc Zapatka, Wolfgang Huber, Thorsten Zenz
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29224130/molecular-epidemiology-and-characterization-of-bovine-leukemia-virus-in-domestic-yaks-bos-grunniens-on-the-qinghai-tibet-plateau-china
#7
Meng Wang, Yun Wang, Abdul Rasheed Baloch, Yangyang Pan, Fang Xu, Lili Tian, Qiaoying Zeng
Bovine leukemia virus (BLV) is a member of the genus Deltaretrovirus of the family Retroviridae and cause a chronic lymphosarcoma, which is extensive in cattle. In yaks (Bos grunniens), the distribution, strains and genetic characteristics of BLV have rarely been studied. The aim of our study was to investigate BLV infections in domestic yaks and determine the genetic variability of BLV circulating in a region of the Qinghai Tibet Plateau, China. Blood samples were collected from 798 yaks, which were from different farms from Gansu, Qinghai and Sichuan provinces surrounding the Qinghai-Tibet Plateau...
December 9, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29222275/the-mutational-landscape-of-chronic-lymphocytic-leukemia-and-its-impact-on-prognosis-and-treatment
#8
REVIEW
Gianluca Gaidano, Davide Rossi
The typical genome of chronic lymphocytic leukemia (CLL) carries ∼2000 molecular lesions. Few mutations recur across patients at a frequency >5%, whereas a large number of biologically and clinically uncharacterized genes are mutated at lower frequency. Approximately 80% of CLL patients carry at least 1 of 4 common chromosomal alterations, namely deletion 13q14, deletion 11q22-23, deletion 17p12, and trisomy 12. Knowledge of the CLL genome has translated into the availability of molecular biomarkers for prognosis and treatment prediction...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222240/old-and-new-tools-in-the-clinical-diagnosis-of-inherited-bone-marrow-failure-syndromes
#9
REVIEW
Allison H West, Jane E Churpek
Patients with inherited bone marrow failure syndromes (IBMFSs) classically present with specific patterns of cytopenias along with congenital anomalies and/or other physical features that are often recognizable early in life. However, increasing application of genomic sequencing and clinical awareness of subtle disease presentations have led to the recognition of IBMFS in pediatric and adult populations more frequently than previously realized, such as those with early onset myelodysplastic syndrome (MDS). Given the well-defined differences in clinical management needs and outcomes for aplastic anemia, acute myeloid leukemia, and MDS in patients with an IBMFS vs those occurring sporadically, as well as nonhematologic comorbidities in patients with IBMFSs, it is critical for hematologists to understand how to approach screening for the currently known IBMFSs...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222235/classification-and-risk-assessment-in-aml-integrating-cytogenetics-and-molecular-profiling
#10
REVIEW
Matahi Moarii, Elli Papaemmanuil
In recent years, the composite molecular architecture in acute myeloid leukemia (AML) has been mapped out. We now have a clearer understanding of the key genetic determinants, the major genetic interactions, and the broad order in which these mutations occur. The next impending challenge is to discern how these recent genomic discoveries define disease biology as well as how to use molecular markers to deliver patient-tailored clinical decision support.
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222170/imprecision-and-dna-break-repair-biased-towards-incompatible-end-joining-in-leukemia
#11
Franz Josef Gassner, Maria Schubert, Stefan Rebhandl, Karina Spandl, Nadja Zaborsky, Kemal Catakovic, Stephanie Blaimer, Daniel Hebenstreit, Richard Greil, Roland Geisberger
Cancer is a genetic disease caused by mutations and chromosomal abnormalities which contribute to uncontrolled cell growth. In addition, cancer cells can rapidly respond to conventional and targeted therapies by accumulating novel and often specific genetic lesions leading to acquired drug resistance and relapsing disease. In chronic lymphocytic leukemia (CLL), however, diverse chromosomal aberrations often occur. In many cases, improper repair of DNA double strand breaks (DSBs) is a major source for genomic abnormalities...
December 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29221753/pura-the-gene-encoding-pur-alpha-member-of-an-ancient-nucleic-acid-binding-protein-family-with-mammalian-neurological-functions
#12
REVIEW
Dianne C Daniel, Edward M Johnson
The PURA gene encodes Pur-alpha, a 322 amino acid protein with repeated nucleic acid binding domains that are highly conserved from bacteria through humans. PUR genes with a single copy of this domain have been detected so far in spirochetes and bacteroides. Lower eukaryotes possess one copy of the PUR gene, whereas chordates possess 1-4 PUR family members. Human PUR genes encode Pur-alpha (Pura), Pur-beta (Purb) and two forms of Pur-gamma (Purg). Pur-alpha is a protein that binds specific DNA and RNA sequence elements...
December 5, 2017: Gene
https://www.readbyqxmd.com/read/29219890/a-cryptic-nup214-abl1-fusion-in-b-cell-precursor-acute-lymphoblastic-leukemia
#13
Shin-Ichi Tsujimoto, Yoshiko Nakano, Tomoo Osumi, Keiko Okada, Meri Ouchi-Uchiyama, Keisuke Kataoka, Yoichi Fujii, Kentaro Ohki, Masafumi Seki, Nobuyoshi Tamagawa, Junko Takita, Seishi Ogawa, Nobutaka Kiyokawa, Junichi Hara, Motohiro Kato
Fluorescent in situ hybridization (FISH) analysis is the standard methods for screening ABL1 fusions, which is recurrently translocated in pediatric acute lymphoblastic leukemia (ALL), and potentially targetable by kinase inhibitors. Here we demonstrated a case of B-cell precursor ALL with NUP214-ABL1 fusion, which break-apart FISH assay for ABL1 failed to detect. The cryptic fusion was generated by small duplication from ABL1 to NUP214, which was detected by copy number analysis using genomic microarray and confirmed by PCR...
December 6, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29214875/genetic-polymorphisms-of-arylamine-n-acetyltransferases-1-and-2-and-the-likelihood-of-developing-pediatric-acute-lymphoblastic-leukemia
#14
Oswaldo Hernández-González, Juan José Ortiz-Zamudio, Cristian Jazmín Rodríguez-Pinal, Ildemar Alvarado-Morales, Verónica Del Carmen Martínez-Jiménez, Raúl Alejandro Salazar-González, Lourdes Cecilia Correa-González, Rocío Gómez, Diana Patricia Portales-Pérez, Rosa Del Carmen Milán-Segovia
Acute lymphoblastic leukemia (ALL) is one of the main causes of death in children and is associated with both genetic susceptibility and environmental factors. Genes encoding the arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2) isoenzymes are highly polymorphic among populations. Single-nucleotide polymorphism analysis was performed by real-time polymerase chain reaction from the genomic DNA of 225 healthy subjects and 57 children with ALL diagnoses. Significant associations were found between the development of ALL and the presence of the haplotypes NAT1*3 (Odds ratio [OR], 2...
December 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29212930/control-of-htlv-1-infection-by-eliminating-envelope-protein-positive-cells-with-recombinant-vesicular-stomatitis-viruses-encoding-htlv-1-primary-receptor
#15
Kenta Tezuka, Kazu Okuma, Madoka Kuramitsu, Sahoko Matsuoka, Reiko Tanaka, Yuetsu Tanaka, Isao Hamaguchi
Human T-cell leukemia virus type 1 (HTLV-1) infection causes adult T-cell leukemia (ATL), which is frequently resistant to current available therapies and has a very poor prognosis. To prevent the development of ATL among carriers it is important to control HTLV-1-infected cells in infected individuals. Therefore, the establishment of novel therapies with drugs specifically targeting infected cells is urgently required. This study aimed to develop a potential therapy by generating recombinant vesicular stomatitis viruses (rVSVs) that lack an envelope glycoprotein G and instead encode HTLV-1 receptor(s) with human glucose transporter 1 (GLUT1), neuropilin 1 (NRP1), or heparan sulfate proteoglycans (HSPGs) including syndecan 1 (SDC1), designated as VSVΔG-GL, VSVΔG-NP, or VSVΔG-SD, respectively...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29209042/analysis-of-the-genomic-landscape-of-multiple-myeloma-highlights-novel-prognostic-markers-and-disease-subgroups
#16
N Bolli, G Biancon, M Moarii, S Gimondi, Y Li, C de Philippis, F Maura, V Sathiaseelan, Y-T Tai, L Mudie, S O'Meara, K Raine, J W Teague, A P Butler, C Carniti, M Gerstung, T Bagratuni, E Kastritis, M Dimopoulos, P Corradini, K Anderson, P Moreau, S Minvielle, P J Campbell, E Papaemmanuil, H Avet-Loiseau, N C Munshi
In multiple myeloma, next generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here, we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number changes (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and IMiD-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene...
December 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29207054/use-of-methylation-profiling-to-identify-significant-differentially-methylated-genes-in-bone-marrow-mesenchymal-stromal-cells-from-acute-myeloid-leukemia
#17
Jing Huang, Zhi Liu, Yufan Sun, Qi Zhong, Li Xu, Ruimin Ou, Cheng Li, Rui Chen, Mengdong Yao, Qing Zhang, Shuang Liu
The present study aimed to characterize the epigenetic architecture by studying the DNA methylation signature in bone marrow mesenchymal stem cells (BM‑MSCs) from patients with acute myeloid leukemia (AML). Microarray dataset GSE79695 was downloaded from the Gene Expression Omnibus database. Differentially methylated sites and differentially methylated CpG islands were identified in BM‑MSC samples from patients with AML compared with controls. MicroRNAs (miRs) encoding genes covering differentially methylated sites were found and the regulation network was constructed...
November 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29194093/cdkn2a-b-deletion-and-double-hit-mutations-of-the-mapk-pathway-underlie-the-aggressive-behavior-of-langerhans-cell-tumors
#18
Luc Xerri, José Adélaïde, Cornel Popovici, Séverine Garnier, Arnaud Guille, Lenaïg Mescam-Mancini, Camille Laurent, Pierre Brousset, Carole Coze, Gérard Michel, Max Chaffanet, Reda Bouabdallah, Diane Coso, François Bertucci, Daniel Birnbaum
Langerhans cell histiocytosis (LCH) has a mostly favorable outcome, whereas Langerhans cell sarcoma (LCS) is an aggressive tumor. It is still unclear whether any specific molecular alterations could underlie the aggressive behavior of Langerhans cell proliferations. We used targeted next-generation sequencing and array-comparative genomic hybridization to profile 22 LCH samples from different patients together with 3 LCS samples corresponding to different relapses from the same patient. The third LCS relapse was a composite tumor including both B-cell chronic lymphocytic leukemia and LCS components...
November 29, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29190891/high-bone-marrow-id2-expression-predicts-poor-chemotherapy-response-and-prognosis-in-acute-myeloid-leukemia
#19
Jing-Dong Zhou, Ji-Chun Ma, Ting-Juan Zhang, Xi-Xi Li, Wei Zhang, De-Hong Wu, Xiang-Mei Wen, Zi-Jun Xu, Jiang Lin, Jun Qian
Dysregulation of ID proteins is a frequent event in various human cancers and has a direct role in cancer initiation, maintenance, progression and drug resistance. Our previous study has revealed ID1 expression and its prognostic value in acute myeloid leukemia (AML). Herein, we further reported ID2 expression and its clinical significance in AML. Real-time quantitative PCR was performed to detect ID2 transcript level in bone marrow mononuclear cells of 145 de novo AML patients. ID2 expression was significantly up-regulated in AML patients compared with controls...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29186366/human-endometrial-stromal-cell-decidualization-requires-transcriptional-reprogramming-by-plzf
#20
Maria M Szwarc, Lan Hai, William E Gibbons, Mary C Peavey, Lisa D White, Qianxing Mo, David M Lonard, Ramakrishna Kommagani, Rainer B Lanz, Francesco J DeMayo, John P Lydon
Infertility and early embryo-miscarriage is linked to inadequate endometrial decidualization. Although transcriptional reprogramming is known to drive decidualization in response to progesterone, the key signaling effectors that directly mediate this hormone response are not fully known. This knowledge-gap is clinically significant because identifying the early signals that directly mediate progesterone-driven decidualization will address some of the current limitations in diagnosing and therapeutically treating patients at most risk for early pregnancy loss...
November 25, 2017: Biology of Reproduction
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