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https://www.readbyqxmd.com/read/29781627/triple-trajectories-of-alcohol-use-tobacco-use-and-depressive-symptoms-as-predictors-of-cannabis-use-disorders-among-urban-adults
#1
Jung Yeon Lee, Judith S Brook, Wonkuk Kim
Heavy cannabis use is associated with a wide array of physical, mental, and functional problems. Therefore, cannabis use disorders (CUDs) may be a major public health concern. Given the adverse health consequences of CUDs, the present study seeks to find possible precursors of CUDs. The current study consisted of 5 waves of data collection from the Harlem Longitudinal Development Study. Among 816 participants, about half are African Americans (52%), and the other half are Puerto Ricans (48%). We used Mplus to obtain the triple trajectories of alcohol use, tobacco use, and depressive symptoms...
May 21, 2018: Psychology of Addictive Behaviors: Journal of the Society of Psychologists in Addictive Behaviors
https://www.readbyqxmd.com/read/29777171/mll-fusion-driven-leukemia-requires-setd2-to-safeguard-genomic-integrity
#2
Anna Skucha, Jessica Ebner, Johannes Schmöllerl, Mareike Roth, Thomas Eder, Adrián César-Razquin, Alexey Stukalov, Sarah Vittori, Matthias Muhar, Bin Lu, Martin Aichinger, Julian Jude, André C Müller, Balázs Győrffy, Christopher R Vakoc, Peter Valent, Keiryn L Bennett, Johannes Zuber, Giulio Superti-Furga, Florian Grebien
MLL-fusions represent a large group of leukemia drivers, whose diversity originates from the vast molecular heterogeneity of C-terminal fusion partners of MLL. While studies of selected MLL-fusions have revealed critical molecular pathways, unifying mechanisms across all MLL-fusions remain poorly understood. We present the first comprehensive survey of protein-protein interactions of seven distantly related MLL-fusion proteins. Functional investigation of 128 conserved MLL-fusion-interactors identifies a specific role for the lysine methyltransferase SETD2 in MLL-leukemia...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29774127/paf1-complex-interactions-with-setdb1-mediate-promoter-h3k9-methylation-and-transcriptional-repression-of-hoxa9-and-meis1-in-acute-myeloid-leukemia
#3
James Ropa, Nirmalya Saha, Zhiling Chen, Justin Serio, Wei Chen, Dattatreya Mellacheruvu, Lili Zhao, Venkatesha Basrur, Alexey I Nesvizhskii, Andrew G Muntean
The Polymerase Associated Factor 1 complex (PAF1c) is an epigenetic co-modifying complex that directly contacts RNA polymerase II (RNAPII) and several epigenetic regulating proteins. Mutations, overexpression and loss of expression of subunits of the PAF1c are observed in various forms of cancer suggesting proper regulation is needed for cellular development. However, the biochemical interactions with the PAF1c that allow dynamic gene regulation are unclear. We and others have shown that the PAF1c makes a direct interaction with MLL fusion proteins, which are potent oncogenic drivers of acute myeloid leukemia (AML)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29766829/acute-myeloid-leukemia-diagnosis-and-management-based-on-current-molecular-genetics-approach
#4
E Suguna, R Farhana, E Kanimozhi, P SaiKumar, G Kumaramanickavel, Chitralekha Sai Kumar
Background &Objective: Acute myeloid leukemia (AML) is characterized by accumulation of ?20% myeloid premature blast cells in the bone marrow and most often found in the peripheral blood. AML is generally classified based on two groups, namely, French-American-British (FAB) and World Health Organization (WHO) systems. For better clinical management, cytogenetic findings in AML are necessary and in patients with normal karyotypes, molecular analysis becomes critical. Mutations of certain genes like Nucleophosmin 1gene (NPM1), Fms-related Tyrosine Kinase 3 (FLT3), CCAAT/Enhancer Binding Protein Alpha (CEBPA), Runt-related transcription factor 1(RUNX1), and Mixed Lineage Leukemia (MLL) play a crucial role in the risk management and clinical stratification of AML patients...
May 15, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29754509/-new-and-traditional-directions-in-the-biology-and-management-of-childhood-acute-lymphoblastic-leukemia
#5
Bálint Egyed, Gábor Kovács, Nóra Kutszegi, Andrea Rzepiel, Judit Csányiné Sági, Dániel János Erdélyi, Judit Müller, Ágnes Félné Semsei
Owing to clinical trials and improvement over the past few decades, the majority of children with acute lymphoblastic leukemia (ALL) survive by first-line chemotherapy and combat with the problems of returning to community. However, many patients may have severe acute or late therapeutic side effects, and the survival rate in some groups (e.g., patients with MLL rearrangements, hypodiploidy, IKZF1 mutation or early precursor T cell phenotype) is far behind the average. Innovative strategies in medical attendance provide better clinical outcomes for them: complete gene diagnostics, molecularly targeted anticancer treatment, immuno-oncology and immune cell therapy...
May 2018: Orvosi Hetilap
https://www.readbyqxmd.com/read/29748211/anti-leukemic-efficacy-of-bet-inhibitor-in-a-preclinical-mouse-model-of-mll-af4-infant-all
#6
Michela Bardini, Luca Trentin, Francesca Rizzo, Margherita Vieri, Angela M Savino, Patricia Garrido Castro, Grazia Fazio, Eddy H J Van Roon, Mark Kerstjens, Nicholas N Smithers, Rab K Prinjha, Geertruy Te Kronnie, Giuseppe Basso, Ronald W Stam, Rob Pieters, Andrea Biondi, Giovanni Cazzaniga
MLL-rearranged acute lymphoblastic leukemia occurring in infants is a rare but very aggressive leukemia, typically associated with a dismal prognosis. Despite the development of specific therapeutic protocols, infant patients with MLL-rearranged ALL still suffer from a low cure rate. At present, novel therapeutic approaches are urgently needed. Recently, the use of small molecule inhibitors targeting the epigenetic regulators of the MLL complex emerged as a promising strategy for the development of a targeted therapy...
May 10, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29748040/cytogenetic-profile-of-moroccan-pediatric-acute-lymphoblastic-leukemia-analysis-of-155-cases-with-a-review-of-the-literature
#7
Zahra Takki Chebihi, Aziza Belkhayat, Elbekkay Chadli, Latifa Hilal, Hanaa Skhoun, Laila Hessissen, Mohamed El Khorassani, Maria El Kababri, Amina Kili, Mohammed Khattab, Youssef Bakri, Nadia Dakka
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, with a peak incidence at 2 to 3 years of age and accounting for almost 30% of all cancers in this age group. It is well established that the identification of cytogenetic abnormalities is highly relevant for the prognosis of and therapeutic decisions in ALL. The purpose of the present study was to define the frequency of recurrent chromosomal abnormalities of ALL in Moroccan patients referred exclusively to the BIOLAB Laboratory of the Children's Hospital of Rabat during a 4-year period and compare our findings to the reported data...
April 25, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29738674/the-complexity-of-blocking-bivalent-protein-protein-interactions-development-of-a-highly-potent-inhibitor-of-the-menin-mixed-lineage-leukemia-mll-interaction
#8
Dmitry Borkin, Szymon Klossowski, Jonathan Pollock, Hongzhi Miao, Brian Linhares, Katarzyna Kempinska, Zhuang Jin, Trupta Purohit, Bo Wen, Miao He, Duxin Sun, Tomasz Cierpicki, Jolanta Grembecka
The protein-protein interaction between menin and Mixed Lineage Leukemia 1 (MLL1) plays an important role in development of acute leukemia with translocations of the MLL1 gene and in solid tumors. Here, we report the development of a new generation of menin-MLL1 inhibitors identified by structure-based optimization of the thienopyrimidine class of compounds. This work resulted in compound 28 (MI-1481), which showed very potent inhibition of the menin-MLL1 interaction (IC50 = 3.6 nM), representing the most potent reversible menin-MLL1 inhibitor reported to date...
May 8, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29730189/design-synthesis-and-biological-evaluation-of-benzo-cd-indol-2-1h-ones-derivatives-as-brd4-inhibitors
#9
Yuxin Feng, Senhao Xiao, Yantao Chen, Hao Jiang, Na Liu, Cheng Luo, Shijie Chen, Hua Chen
Compound 1 bearing with benzo [cd]indol-2(1H)-one scaffold was identified as an effective BRD4 inhibitor through the AlphaScreen-based high-throughput screening and its high-resolution crystal structure with BRD4_BD1 protein. A series of 48 compounds were designed and synthesized by structural optimization on compound 1. All the compounds have been evaluated for their BRD4 inhibitory activities. The results showed that compounds 23, 24, 28 and 44 are the most potential ones with the IC50 values of 1.02 μM, 1...
April 28, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29728108/decitabine-demonstrates-antileukemic-activity-in-b-cell-precursor-acute-lymphoblastic-leukemia-with-mll-rearrangements
#10
C Roolf, A Richter, C Konkolefski, G Knuebel, A Sekora, S Krohn, J Stenzel, B J Krause, B Vollmar, H Murua Escobar, C Junghanss
BACKGROUND: Promotor hypermethylation of CpG islands is common in B cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed lineage leukemia (MLL) gene rearrangements. Hypomethylating agents (HMA) such as azacitidine (AZA) and decitabine (DEC) reduce DNA hypermethylation by incorporation into DNA and were successfully introduced into the clinic for the treatment of myeloid neoplasias. METHODS: Here, we investigated whether HMA induce comparable biological effects in MLL-positive BCP-ALL...
May 4, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29724899/the-dot1l-inhibitor-pinometostat-reduces-h3k79-methylation-and-has-modest-clinical-activity-in-adult-acute-leukemia
#11
Eytan M Stein, Guillermo Garcia-Manero, David A Rizzieri, Raoul Tibes, Jesus G Berdeja, Michael R Savona, Mojca Jongen-Lavrenic, Jessica K Altman, Blythe Thomson, Stephen J Blakemore, Scott R Daigle, Nigel J Waters, A Benjamin Suttle, Alicia Clawson, Roy Pollock, Andrei Krivtsov, Scott A Armstrong, Jorge DiMartino, Eric Hedrick, Bob Löwenberg, Martin S Tallman
Pinometostat (EPZ-5676) is a first-in-class, small-molecule inhibitor of the histone methyltransferase DOT1L. In this phase 1 study, pinometostat was evaluated for safety and efficacy in adult patients with advanced acute leukemias, particularly those involving MLL rearrangements ( MLL-r ) resulting from 11q23 translocations. Fifty-one patients were enrolled into 6 dose escalation cohorts (n=26) and 2 expansion cohorts (n=25) at pinometostat doses of 54 and 90 mg/m2 /day by continuous intravenous infusion in 28-day cycles...
May 3, 2018: Blood
https://www.readbyqxmd.com/read/29721197/backtracked-analysis-of-preleukemic-fusion-genes-and-dna-repair-foci-in-umbilical-cord-blood-of-children-with-acute-leukemia
#12
Milan Škorvaga, Matúš Durdík, Pavol Košík, Eva Marková, Marek Holop, Miroslav Kubeš, Judita Puškáčová, Alexandra Kolenová, Igor Belyaev
The first event in origination of many childhood leukemias is a specific preleukemic fusion gene (PFG) that arises, often in utero, in hematopoietic stem/progenitor cells (HSPC) from misrepaired DNA double strand break (DSB). An immanently elevated level of DSB and impaired apoptosis may contribute to origination and persistence of PFG and donor cell-derived leukemia in recipients of allogeneic transplantation of umbilical cord blood (UCB). We investigated DSB, apoptosis and PFG in the backtracked UCB cells of leukemic patients...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29720585/de-novo-activating-mutations-drive-clonal-evolution-and-enhance-clonal-fitness-in-kmt2a-rearranged-leukemia
#13
Axel Hyrenius-Wittsten, Mattias Pilheden, Helena Sturesson, Jenny Hansson, Michael P Walsh, Guangchun Song, Julhash U Kazi, Jian Liu, Ramprasad Ramakrishan, Cristian Garcia-Ruiz, Stephanie Nance, Pankaj Gupta, Jinghui Zhang, Lars Rönnstrand, Anne Hultquist, James R Downing, Karin Lindkvist-Petersson, Kajsa Paulsson, Marcus Järås, Tanja A Gruber, Jing Ma, Anna K Hagström-Andersson
Activating signaling mutations are common in acute leukemia with KMT2A (previously MLL) rearrangements (KMT2A-R). These mutations are often subclonal and their biological impact remains unclear. Using a retroviral acute myeloid mouse leukemia model, we demonstrate that FLT3 ITD , FLT3 N676K , and NRAS G12D accelerate KMT2A-MLLT3 leukemia onset. Further, also subclonal FLT3 N676K mutations accelerate disease, possibly by providing stimulatory factors. Herein, we show that one such factor, MIF, promotes survival of mouse KMT2A-MLLT3 leukemia initiating cells...
May 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29718303/the-kdm4a-kdm4c-nf-%C3%AE%C2%BAb-and-wdr5-epigenetic-cascade-regulates-the-activation-of-b-cells
#14
Kuo-Hsuan Hung, Yong H Woo, I-Ying Lin, Chin-Hsiu Liu, Li-Chieh Wang, Hsin-Yu Chen, Bor-Luen Chiang, Kuo-I Lin
T follicular helper (Tfh) cell-derived signals promote activation and proliferation of antigen-primed B cells. It remains unclear whether epigenetic regulation is involved in the B cell responses to Tfh cell-derived signals. Here, we demonstrate that Tfh cell-mimicking signals induce the expression of histone demethylases KDM4A and KDM4C, and the concomitant global down-regulation of their substrates, H3K9me3/me2, in B cells. Depletion of KDM4A and KDM4C potentiates B cell activation and proliferation in response to Tfh cell-derived signals...
April 30, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29713832/assessment-of-myofascial-medialization-following-posterior-component-separation-via-transversus-abdominis-muscle-release-in-a-cadaveric-model
#15
A Majumder, H J Miller, L M Del Campo, H Soltanian, Y W Novitsky
PURPOSE: Posterior component separation (PCS) via the transversus abdominis release (TAR) procedure continues to gain popularity. However, neither the physiologic basis nor the extent of myofascial medialization after TAR is established. We aimed to assess both anterior and posterior rectus fascia (AF and PF) medialization following each step of the TAR procedure. METHODS: Ten fresh cadavers underwent PCS via TAR. Steps included midline laparotomy (MLL), retrorectus dissection (RRD), incision of the posterior rectus sheath (IPL), transversus abdominis muscle division (TAD), and retromuscular dissection (RMD)...
April 30, 2018: Hernia: the Journal of Hernias and Abdominal Wall Surgery
https://www.readbyqxmd.com/read/29694837/planarian-flatworms-as-a-new-model-system-for-understanding-epigenetic-regulation-of-stem-cell-pluripotency-and-differentiation
#16
REVIEW
Anish Dattani, Divya Sridhar, Aziz Aboobaker
Planarian flatworms possess pluripotent stem cells (neoblasts) that are able to differentiate into all cell types that constitute the adult body plan. Consequently, planarians possess remarkable regenerative capabilities. Transcriptomic studies have revealed that gene expression is coordinated to maintain neoblast pluripotency, and ensure correct lineage specification during differentiation. But as yet they have not revealed how this regulation of expression is controlled. In this review, we propose that planarians represent a unique and effective system to study the epigenetic regulation of these processes in an in vivo context...
April 22, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29694435/invasion-of-sorghum-in-the-americas-by-a-new-sugarcane-aphid-melanaphis-sacchari-superclone
#17
Samuel Nibouche, Laurent Costet, Jocelyn R Holt, Alana Jacobson, Adrian Pekarcik, Joëlle Sadeyen, J Scott Armstrong, Gary C Peterson, Neal McLaren, Raul F Medina
In the United States (US), the sugarcane aphid (SCA) Melanaphis sacchari (Zehnter) (Hemiptera: Aphididae) was introduced in the 1970s, however at that time it was only considered a pest of sugarcane. In 2013, a massive outbreak of M. sacchari occured on sorghum, resulting in significant economic damage to sorghum grown in North America including the US, Mexico, and Puerto Rico. The aim of the present study was to determine if the SCA pest emergence in American sorghum resulted from the introduction of new genotypes...
2018: PloS One
https://www.readbyqxmd.com/read/29692408/the-basic-helix-loop-helix-transcription-factor-sharp1-is-an-oncogenic-driver-in-mll-af6-acute-myelogenous-leukemia
#18
Akihiko Numata, Hui Si Kwok, Akira Kawasaki, Jia Li, Qi-Ling Zhou, Jon Kerry, Touati Benoukraf, Deepak Bararia, Feng Li, Erica Ballabio, Marta Tapia, Aniruddha J Deshpande, Robert S Welner, Ruud Delwel, Henry Yang, Thomas A Milne, Reshma Taneja, Daniel G Tenen
Acute Myeloid Leukemia (AML) with MLL gene rearrangements demonstrate unique gene expression profiles driven by MLL-fusion proteins. Here, we identify the circadian clock transcription factor SHARP1 as a novel oncogenic target in MLL-AF6 AML, which has the worst prognosis among all subtypes of MLL-rearranged AMLs. SHARP1 is expressed solely in MLL-AF6 AML, and its expression is regulated directly by MLL-AF6/DOT1L. Suppression of SHARP1 induces robust apoptosis of human MLL-AF6 AML cells. Genetic deletion in mice delays the development of leukemia and attenuated leukemia-initiating potential, while sparing normal hematopoiesis...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29672864/menin-regulates-the-serine-biosynthetic-pathway-in-ewing-sarcoma
#19
Laurie K Svoboda, Selina Shiqing K Teh, Sudha Sud, Samuel Kerk, Aaron Zebolsky, Sydney Treichel, Dafydd Thomas, Christopher J Halbrook, Ho-Joon Lee, Daniel Kremer, Li Zhang, Szymon Klossowski, Armand R Bankhead, Brian Magnuson, Mats Ljungman, Tomasz Cierpicki, Jolanta Grembecka, Costas A Lyssiotis, Elizabeth R Lawlor
Developmental transcription programs are epigenetically regulated by multi-protein complexes, including the menin- and MLL-containing trithorax (TrxG) complexes, which promote gene transcription by depositing the H3K4me3 activating mark at target gene promoters. We recently reported that in Ewing sarcoma, MLL1 (lysine methyltransferase 2A, KMT2A) and menin are overexpressed and function as oncogenes. Small molecule inhibition of the menin-MLL interaction leads to loss of menin and MLL1 protein expression and to inhibition of growth and tumorigenicity...
April 19, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29666671/the-comparative-experimental-study-of-multilabel-classification-for-diagnosis-assistant-based-on-chinese-obstetric-emrs
#20
Kunli Zhang, Hongchao Ma, Yueshu Zhao, Hongying Zan, Lei Zhuang
Obstetric electronic medical records (EMRs) contain massive amounts of medical data and health information. The information extraction and diagnosis assistants of obstetric EMRs are of great significance in improving the fertility level of the population. The admitting diagnosis in the first course record of the EMR is reasoned from various sources, such as chief complaints, auxiliary examinations, and physical examinations. This paper treats the diagnosis assistant as a multilabel classification task based on the analyses of obstetric EMRs...
2018: Journal of Healthcare Engineering
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