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https://www.readbyqxmd.com/read/28640953/overview-of-transgenic-mouse-models-of-myeloproliferative-neoplasms-mpns
#1
Andrew Dunbar, Abbas Nazir, Ross Levine
Myeloproliferative neoplasms (MPNs) are a class of hematologic diseases characterized by aberrant proliferation of one or more myeloid lineages and progressive bone marrow fibrosis. In 2005, seminal work by multiple groups identified the JAK2V617F mutation in a significant fraction of MPN patients. Since that time, murine models of JAK2V617F have greatly enhanced the understanding of the role of aberrant JAK-STAT signaling in MPN pathogenesis and have provided an in vivo pre-clinical platform that can be used to develop novel therapies...
June 22, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/28621973/gw170104-observation-of-a-50-solar-mass-binary-black-hole-coalescence-at-redshift-0-2
#2
B P Abbott, R Abbott, T D Abbott, F Acernese, K Ackley, C Adams, T Adams, P Addesso, R X Adhikari, V B Adya, C Affeldt, M Afrough, B Agarwal, M Agathos, K Agatsuma, N Aggarwal, O D Aguiar, L Aiello, A Ain, P Ajith, B Allen, G Allen, A Allocca, P A Altin, A Amato, A Ananyeva, S B Anderson, W G Anderson, S Antier, S Appert, K Arai, M C Araya, J S Areeda, N Arnaud, K G Arun, S Ascenzi, G Ashton, M Ast, S M Aston, P Astone, P Aufmuth, C Aulbert, K AultONeal, A Avila-Alvarez, S Babak, P Bacon, M K M Bader, S Bae, P T Baker, F Baldaccini, G Ballardin, S W Ballmer, S Banagiri, J C Barayoga, S E Barclay, B C Barish, D Barker, F Barone, B Barr, L Barsotti, M Barsuglia, D Barta, J Bartlett, I Bartos, R Bassiri, A Basti, J C Batch, C Baune, M Bawaj, M Bazzan, B Bécsy, C Beer, M Bejger, I Belahcene, A S Bell, B K Berger, G Bergmann, C P L Berry, D Bersanetti, A Bertolini, J Betzwieser, S Bhagwat, R Bhandare, I A Bilenko, G Billingsley, C R Billman, J Birch, R Birney, O Birnholtz, S Biscans, A Bisht, M Bitossi, C Biwer, M A Bizouard, J K Blackburn, J Blackman, C D Blair, D G Blair, R M Blair, S Bloemen, O Bock, N Bode, M Boer, G Bogaert, A Bohe, F Bondu, R Bonnand, B A Boom, R Bork, V Boschi, S Bose, Y Bouffanais, A Bozzi, C Bradaschia, P R Brady, V B Braginsky, M Branchesi, J E Brau, T Briant, A Brillet, M Brinkmann, V Brisson, P Brockill, J E Broida, A F Brooks, D A Brown, D D Brown, N M Brown, S Brunett, C C Buchanan, A Buikema, T Bulik, H J Bulten, A Buonanno, D Buskulic, C Buy, R L Byer, M Cabero, L Cadonati, G Cagnoli, C Cahillane, J Calderón Bustillo, T A Callister, E Calloni, J B Camp, M Canepa, P Canizares, K C Cannon, H Cao, J Cao, C D Capano, E Capocasa, F Carbognani, S Caride, M F Carney, J Casanueva Diaz, C Casentini, S Caudill, M Cavaglià, F Cavalier, R Cavalieri, G Cella, C B Cepeda, L Cerboni Baiardi, G Cerretani, E Cesarini, S J Chamberlin, M Chan, S Chao, P Charlton, E Chassande-Mottin, D Chatterjee, K Chatziioannou, B D Cheeseboro, H Y Chen, Y Chen, H-P Cheng, A Chincarini, A Chiummo, T Chmiel, H S Cho, M Cho, J H Chow, N Christensen, Q Chu, A J K Chua, S Chua, A K W Chung, S Chung, G Ciani, R Ciolfi, C E Cirelli, A Cirone, F Clara, J A Clark, F Cleva, C Cocchieri, E Coccia, P-F Cohadon, A Colla, C G Collette, L R Cominsky, M Constancio, L Conti, S J Cooper, P Corban, T R Corbitt, K R Corley, N Cornish, A Corsi, S Cortese, C A Costa, M W Coughlin, S B Coughlin, J-P Coulon, S T Countryman, P Couvares, P B Covas, E E Cowan, D M Coward, M J Cowart, D C Coyne, R Coyne, J D E Creighton, T D Creighton, J Cripe, S G Crowder, T J Cullen, A Cumming, L Cunningham, E Cuoco, T Dal Canton, S L Danilishin, S D'Antonio, K Danzmann, A Dasgupta, C F Da Silva Costa, V Dattilo, I Dave, M Davier, D Davis, E J Daw, B Day, S De, D DeBra, E Deelman, J Degallaix, M De Laurentis, S Deléglise, W Del Pozzo, T Denker, T Dent, V Dergachev, R De Rosa, R T DeRosa, R DeSalvo, J Devenson, R C Devine, S Dhurandhar, M C Díaz, L Di Fiore, M Di Giovanni, T Di Girolamo, A Di Lieto, S Di Pace, I Di Palma, F Di Renzo, Z Doctor, V Dolique, F Donovan, K L Dooley, S Doravari, I Dorrington, R Douglas, M Dovale Álvarez, T P Downes, M Drago, R W P Drever, J C Driggers, Z Du, M Ducrot, J Duncan, S E Dwyer, T B Edo, M C Edwards, A Effler, H-B Eggenstein, P Ehrens, J Eichholz, S S Eikenberry, R A Eisenstein, R C Essick, Z B Etienne, T Etzel, M Evans, T M Evans, M Factourovich, V Fafone, H Fair, S Fairhurst, X Fan, S Farinon, B Farr, W M Farr, E J Fauchon-Jones, M Favata, M Fays, H Fehrmann, J Feicht, M M Fejer, A Fernandez-Galiana, I Ferrante, E C Ferreira, F Ferrini, F Fidecaro, I Fiori, D Fiorucci, R P Fisher, R Flaminio, M Fletcher, H Fong, P W F Forsyth, S S Forsyth, J-D Fournier, S Frasca, F Frasconi, Z Frei, A Freise, R Frey, V Frey, E M Fries, P Fritschel, V V Frolov, P Fulda, M Fyffe, H Gabbard, M Gabel, B U Gadre, S M Gaebel, J R Gair, L Gammaitoni, M R Ganija, S G Gaonkar, F Garufi, S Gaudio, G Gaur, V Gayathri, N Gehrels, G Gemme, E Genin, A Gennai, D George, J George, L Gergely, V Germain, S Ghonge, Abhirup Ghosh, Archisman Ghosh, S Ghosh, J A Giaime, K D Giardina, A Giazotto, K Gill, L Glover, E Goetz, R Goetz, S Gomes, G González, J M Gonzalez Castro, A Gopakumar, M L Gorodetsky, S E Gossan, M Gosselin, R Gouaty, A Grado, C Graef, M Granata, A Grant, S Gras, C Gray, G Greco, A C Green, P Groot, H Grote, S Grunewald, P Gruning, G M Guidi, X Guo, A Gupta, M K Gupta, K E Gushwa, E K Gustafson, R Gustafson, B R Hall, E D Hall, G Hammond, M Haney, M M Hanke, J Hanks, C Hanna, M D Hannam, O A Hannuksela, J Hanson, T Hardwick, J Harms, G M Harry, I W Harry, M J Hart, C-J Haster, K Haughian, J Healy, A Heidmann, M C Heintze, H Heitmann, P Hello, G Hemming, M Hendry, I S Heng, J Hennig, J Henry, A W Heptonstall, M Heurs, S Hild, D Hoak, D Hofman, K Holt, D E Holz, P Hopkins, C Horst, J Hough, E A Houston, E J Howell, Y M Hu, E A Huerta, D Huet, B Hughey, S Husa, S H Huttner, T Huynh-Dinh, N Indik, D R Ingram, R Inta, G Intini, H N Isa, J-M Isac, M Isi, B R Iyer, K Izumi, T Jacqmin, K Jani, P Jaranowski, S Jawahar, F Jiménez-Forteza, W W Johnson, N K Johnson-McDaniel, D I Jones, R Jones, R J G Jonker, L Ju, J Junker, C V Kalaghatgi, V Kalogera, S Kandhasamy, G Kang, J B Kanner, S Karki, K S Karvinen, M Kasprzack, M Katolik, E Katsavounidis, W Katzman, S Kaufer, K Kawabe, F Kéfélian, D Keitel, A J Kemball, R Kennedy, C Kent, J S Key, F Y Khalili, I Khan, S Khan, Z Khan, E A Khazanov, N Kijbunchoo, Chunglee Kim, J C Kim, W Kim, W S Kim, Y-M Kim, S J Kimbrell, E J King, P J King, R Kirchhoff, J S Kissel, L Kleybolte, S Klimenko, P Koch, S M Koehlenbeck, S Koley, V Kondrashov, A Kontos, M Korobko, W Z Korth, I Kowalska, D B Kozak, C Krämer, V Kringel, B Krishnan, A Królak, G Kuehn, P Kumar, R Kumar, S Kumar, L Kuo, A Kutynia, S Kwang, B D Lackey, K H Lai, M Landry, R N Lang, J Lange, B Lantz, R K Lanza, A Lartaux-Vollard, P D Lasky, M Laxen, A Lazzarini, C Lazzaro, P Leaci, S Leavey, C H Lee, H K Lee, H M Lee, H W Lee, K Lee, J Lehmann, A Lenon, M Leonardi, N Leroy, N Letendre, Y Levin, T G F Li, A Libson, T B Littenberg, J Liu, R K L Lo, N A Lockerbie, L T London, J E Lord, M Lorenzini, V Loriette, M Lormand, G Losurdo, J D Lough, G Lovelace, H Lück, D Lumaca, A P Lundgren, R Lynch, Y Ma, S Macfoy, B Machenschalk, M MacInnis, D M Macleod, I Magaña Hernandez, F Magaña-Sandoval, L Magaña Zertuche, R M Magee, E Majorana, I Maksimovic, N Man, V Mandic, V Mangano, G L Mansell, M Manske, M Mantovani, F Marchesoni, F Marion, S Márka, Z Márka, C Markakis, A S Markosyan, E Maros, F Martelli, L Martellini, I W Martin, D V Martynov, J N Marx, K Mason, A Masserot, T J Massinger, M Masso-Reid, S Mastrogiovanni, A Matas, F Matichard, L Matone, N Mavalvala, R Mayani, N Mazumder, R McCarthy, D E McClelland, S McCormick, L McCuller, S C McGuire, G McIntyre, J McIver, D J McManus, T McRae, S T McWilliams, D Meacher, G D Meadors, J Meidam, E Mejuto-Villa, A Melatos, G Mendell, R A Mercer, E L Merilh, M Merzougui, S Meshkov, C Messenger, C Messick, R Metzdorff, P M Meyers, F Mezzani, H Miao, C Michel, H Middleton, E E Mikhailov, L Milano, A L Miller, A Miller, B B Miller, J Miller, M Millhouse, O Minazzoli, Y Minenkov, J Ming, C Mishra, S Mitra, V P Mitrofanov, G Mitselmakher, R Mittleman, A Moggi, M Mohan, S R P Mohapatra, M Montani, B C Moore, C J Moore, D Moraru, G Moreno, S R Morriss, B Mours, C M Mow-Lowry, G Mueller, A W Muir, Arunava Mukherjee, D Mukherjee, S Mukherjee, N Mukund, A Mullavey, J Munch, E A M Muniz, P G Murray, K Napier, I Nardecchia, L Naticchioni, R K Nayak, G Nelemans, T J N Nelson, M Neri, M Nery, A Neunzert, J M Newport, G Newton, K K Y Ng, T T Nguyen, D Nichols, A B Nielsen, S Nissanke, A Nitz, A Noack, F Nocera, D Nolting, M E N Normandin, L K Nuttall, J Oberling, E Ochsner, E Oelker, G H Ogin, J J Oh, S H Oh, F Ohme, M Oliver, P Oppermann, Richard J Oram, B O'Reilly, R Ormiston, L F Ortega, R O'Shaughnessy, D J Ottaway, H Overmier, B J Owen, A E Pace, J Page, M A Page, A Pai, S A Pai, J R Palamos, O Palashov, C Palomba, A Pal-Singh, H Pan, B Pang, P T H Pang, C Pankow, F Pannarale, B C Pant, F Paoletti, A Paoli, M A Papa, H R Paris, W Parker, D Pascucci, A Pasqualetti, R Passaquieti, D Passuello, B Patricelli, B L Pearlstone, M Pedraza, R Pedurand, L Pekowsky, A Pele, S Penn, C J Perez, A Perreca, L M Perri, H P Pfeiffer, M Phelps, O J Piccinni, M Pichot, F Piergiovanni, V Pierro, G Pillant, L Pinard, I M Pinto, M Pitkin, R Poggiani, P Popolizio, E K Porter, A Post, J Powell, J Prasad, J W W Pratt, V Predoi, T Prestegard, M Prijatelj, M Principe, S Privitera, G A Prodi, L G Prokhorov, O Puncken, M Punturo, P Puppo, M Pürrer, H Qi, J Qin, S Qiu, V Quetschke, E A Quintero, R Quitzow-James, F J Raab, D S Rabeling, H Radkins, P Raffai, S Raja, C Rajan, M Rakhmanov, K E Ramirez, P Rapagnani, V Raymond, M Razzano, J Read, T Regimbau, L Rei, S Reid, D H Reitze, H Rew, S D Reyes, F Ricci, P M Ricker, S Rieger, K Riles, M Rizzo, N A Robertson, R Robie, F Robinet, A Rocchi, L Rolland, J G Rollins, V J Roma, J D Romano, R Romano, C L Romel, J H Romie, D Rosińska, M P Ross, S Rowan, A Rüdiger, P Ruggi, K Ryan, M Rynge, S Sachdev, T Sadecki, L Sadeghian, M Sakellariadou, L Salconi, M Saleem, F Salemi, A Samajdar, L Sammut, L M Sampson, E J Sanchez, V Sandberg, B Sandeen, J R Sanders, B Sassolas, B S Sathyaprakash, P R Saulson, O Sauter, R L Savage, A Sawadsky, P Schale, J Scheuer, E Schmidt, J Schmidt, P Schmidt, R Schnabel, R M S Schofield, A Schönbeck, E Schreiber, D Schuette, B W Schulte, B F Schutz, S G Schwalbe, J Scott, S M Scott, E Seidel, D Sellers, A S Sengupta, D Sentenac, V Sequino, A Sergeev, D A Shaddock, T J Shaffer, A A Shah, M S Shahriar, L Shao, B Shapiro, P Shawhan, A Sheperd, D H Shoemaker, D M Shoemaker, K Siellez, X Siemens, M Sieniawska, D Sigg, A D Silva, A Singer, L P Singer, A Singh, R Singh, A Singhal, A M Sintes, B J J Slagmolen, B Smith, J R Smith, R J E Smith, E J Son, J A Sonnenberg, B Sorazu, F Sorrentino, T Souradeep, A P Spencer, A K Srivastava, A Staley, M Steinke, J Steinlechner, S Steinlechner, D Steinmeyer, B C Stephens, S P Stevenson, R Stone, K A Strain, G Stratta, S E Strigin, R Sturani, A L Stuver, T Z Summerscales, L Sun, S Sunil, P J Sutton, B L Swinkels, M J Szczepańczyk, M Tacca, D Talukder, D B Tanner, M Tápai, A Taracchini, J A Taylor, R Taylor, T Theeg, E G Thomas, M Thomas, P Thomas, K A Thorne, K S Thorne, E Thrane, S Tiwari, V Tiwari, K V Tokmakov, K Toland, M Tonelli, Z Tornasi, C I Torrie, D Töyrä, F Travasso, G Traylor, D Trifirò, J Trinastic, M C Tringali, L Trozzo, K W Tsang, M Tse, R Tso, D Tuyenbayev, K Ueno, D Ugolini, C S Unnikrishnan, A L Urban, S A Usman, K Vahi, H Vahlbruch, G Vajente, G Valdes, M Vallisneri, N van Bakel, M van Beuzekom, J F J van den Brand, C Van Den Broeck, D C Vander-Hyde, L van der Schaaf, J V van Heijningen, A A van Veggel, M Vardaro, V Varma, S Vass, M Vasúth, A Vecchio, G Vedovato, J Veitch, P J Veitch, K Venkateswara, G Venugopalan, D Verkindt, F Vetrano, A Viceré, A D Viets, S Vinciguerra, D J Vine, J-Y Vinet, S Vitale, T Vo, H Vocca, C Vorvick, D V Voss, W D Vousden, S P Vyatchanin, A R Wade, L E Wade, M Wade, R M Wald, R Walet, M Walker, L Wallace, S Walsh, G Wang, H Wang, J Z Wang, M Wang, Y-F Wang, Y Wang, R L Ward, J Warner, M Was, J Watchi, B Weaver, L-W Wei, M Weinert, A J Weinstein, R Weiss, L Wen, E K Wessel, P Weßels, T Westphal, K Wette, J T Whelan, B F Whiting, C Whittle, D Williams, R D Williams, A R Williamson, J L Willis, B Willke, M H Wimmer, W Winkler, C C Wipf, H Wittel, G Woan, J Woehler, J Wofford, K W K Wong, J Worden, J L Wright, D S Wu, G Wu, W Yam, H Yamamoto, C C Yancey, M J Yap, Hang Yu, Haocun Yu, M Yvert, A Zadrożny, M Zanolin, T Zelenova, J-P Zendri, M Zevin, L Zhang, M Zhang, T Zhang, Y-H Zhang, C Zhao, M Zhou, Z Zhou, X J Zhu, A Zimmerman, M E Zucker, J Zweizig
We describe the observation of GW170104, a gravitational-wave signal produced by the coalescence of a pair of stellar-mass black holes. The signal was measured on January 4, 2017 at 10∶11:58.6 UTC by the twin advanced detectors of the Laser Interferometer Gravitational-Wave Observatory during their second observing run, with a network signal-to-noise ratio of 13 and a false alarm rate less than 1 in 70 000 years. The inferred component black hole masses are 31.2_{-6.0}^{+8.4}M_{⊙} and 19.4_{-5.9}^{+5...
June 2, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28591523/completion-dissection-or-observation-for-sentinel-node-metastasis-in-melanoma
#3
RANDOMIZED CONTROLLED TRIAL
Mark B Faries, John F Thompson, Alistair J Cochran, Robert H Andtbacka, Nicola Mozzillo, Jonathan S Zager, Tiina Jahkola, Tawnya L Bowles, Alessandro Testori, Peter D Beitsch, Harald J Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W J M Wouters, Michael S Sabel, Edward A Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R Rossi, Rogerio I Neves, Steven D Trocha, Frances Wright, David R Byrd, Maurice Matter, Eddy Hsueh, Alastair MacKenzie-Ross, Douglas B Johnson, Patrick Terheyden, Adam C Berger, Tara L Huston, Jeffrey D Wayne, B Mark Smithers, Heather B Neuman, Schlomo Schneebaum, Jeffrey E Gershenwald, Charlotte E Ariyan, Darius C Desai, Lisa Jacobs, Kelly M McMasters, Anja Gesierich, Peter Hersey, Steven D Bines, John M Kane, Richard J Barth, Gregory McKinnon, Jeffrey M Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A Hoefer, James M Lewis, Randall Scheri, Mark C Kelley, Omgo E Nieweg, R Dirk Noyes, Dave S B Hoon, He-Jing Wang, David A Elashoff, Robert M Elashoff
BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group)...
June 8, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28588020/enasidenib-in-mutant-idh2-relapsed-or-refractory-acute-myeloid-leukemia
#4
Eytan M Stein, Courtney D DiNardo, Daniel A Pollyea, Amir T Fathi, Gail J Roboz, Jessica K Altman, Richard M Stone, Daniel J DeAngelo, Ross L Levine, Ian W Flinn, Hagop M Kantarjian, Robert Collins, Manish R Patel, Arthur E Frankel, Anthony Stein, Mikkael A Sekeres, Ronan T Swords, Bruno C Medeiros, Christophe Willekens, Paresh Vyas, Alessandra Tosolini, Qiang Xu, Robert D Knight, Katharine E Yen, Sam Agresta, Stéphane de Botton, Martin S Tallman
Recurrent mutations in isocitrate dehydrogenase 2 (IDH2) occur in ~12% of patients with acute myeloid leukemia (AML). Mutated IDH2 proteins neomorphically synthesize 2-hydroxyglutarate resulting in DNA and histone hypermethylation, leading to blocked cellular differentiation. Enasidenib (AG-221/CC-90007) is a first-in-class, oral, selective inhibitor of mutant-IDH2 enzymes. This first-in-human, phase 1/2 study assessed the maximum tolerated dose (MTD), pharmacokinetic and pharmacodynamic profiles, safety, and clinical activity of enasidenib in patients with mutant-IDH2 advanced myeloid malignancies...
June 6, 2017: Blood
https://www.readbyqxmd.com/read/28588019/enasidenib-induces-acute-myeloid-leukemia-cell-differentiation-to-promote-clinical-response
#5
Michael D Amatangelo, Lynn Quek, Alan Shih, Eytan M Stein, Mikhail Roshal, Muriel D David, Benoit Marteyn, Noushin Rahnamay Farnoud, Stephane de Botton, Olivier A Bernard, Bin Wu, Katharine E Yen, Martin S Tallman, Elli Papaemmanuil, Virginie Penard-Lacronique, Anjan Thakurta, Paresh Vyas, Ross L Levine
Recurrent mutations at R140 and R172 in isocitrate dehydrogenase 2 (IDH2) occur in many cancers, including ~12% of acute myeloid leukemia (AML). In preclinical models these mutations cause accumulation of the oncogenic metabolite R-2-hydroxyglutarate (2-HG) and induce hematopoietic differentiation block. Single-agent enasidenib (AG-221/CC-90007), a selective mutant IDH2 (mIDH2) inhibitor, produced an overall response rate of 40.3% in relapsed/refractory AML patients with mIDH2 in a phase 1 trial. However, its mechanism of action and biomarkers associated with response remain unclear...
June 6, 2017: Blood
https://www.readbyqxmd.com/read/28576974/lecithin-cholesterol-acyltransferase-activation-by-sulfhydryl-reactive-small-molecules-role-of-cysteine-31
#6
Lita A Freeman, Stephen J Demosky, Monika Konaklieva, Rostislav Kuskovsky, Angel Aponte, Alice F Ossoli, Scott M Gordon, Ross F Koby, Kelly A Manthei, Min Shen, Boris Vaisman, Robert D Shamburek, Ajit Jadhav, Laura Calabresi, Marjan Gucek, John J G Tesmer, Rodney L Levine, Alan T Remaley
BACKGROUND: Lecithin:cholesterol acyltransferase (LCAT) catalyzes plasma cholesteryl ester formation and is defective in Familial LCAT Deficiency (FLD), an autosomal recessive disorder characterized by low HDL, anemia and renal disease. OBJECTIVE: To investigate the mechanism by which Compound A, a small heterocyclic amine, activates LCAT. METHODS: Effect of Compound A on LCAT was tested in human plasma and with recombinant LCAT. Mass spectrometry and NMR was used to determine Compound A adduct formation with LCAT...
June 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28436985/functional-screen-of-msi2-interactors-identifies-an-essential-role-for-syncrip-in-myeloid-leukemia-stem-cells
#7
Ly P Vu, Camila Prieto, Elianna M Amin, Sagar Chhangawala, Andrei Krivtsov, M Nieves Calvo-Vidal, Timothy Chou, Arthur Chow, Gerard Minuesa, Sun Mi Park, Trevor S Barlowe, James Taggart, Patrick Tivnan, Raquel P Deering, Lisa P Chu, Jeong-Ah Kwon, Cem Meydan, Javier Perales-Paton, Arora Arshi, Mithat Gönen, Christopher Famulare, Minal Patel, Elisabeth Paietta, Martin S Tallman, Yuheng Lu, Jacob Glass, Francine E Garret-Bakelman, Ari Melnick, Ross Levine, Fatima Al-Shahrour, Marcus Järås, Nir Hacohen, Alexia Hwang, Ralph Garippa, Christopher J Lengner, Scott A Armstrong, Leandro Cerchietti, Glenn S Cowley, David Root, John Doench, Christina Leslie, Benjamin L Ebert, Michael G Kharas
The identity of the RNA-binding proteins (RBPs) that govern cancer stem cells remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomic analysis of the MSI2-interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia. Syncrip was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis...
June 2017: Nature Genetics
https://www.readbyqxmd.com/read/28408400/epigenetic-identity-in-aml-depends-on-disruption-of-non-promoter-regulatory-elements-and-is-affected-by-antagonistic-effects-of-mutations-in-epigenetic-modifiers
#8
Jacob Glass, Duane C Hassane, Bas Wouters, Hiroyoshi Kunimoto, Roberto Avellino, Francine E Garrett-Bakelman, Olga A Guryanova, Robert Bowman, Shira Redlich, Andrew Intlekofer, Cem Meydan, Tingting Qin, Mame P Fall, Alicia Alonso, Monica L Guzman, Peter Jm Valk, Craig B Thompson, Ross L Levine, Olivier Elemento, Ruud Delwel, Ari Melnick, Maria E Figueroa
Aberrant DNA methylation of gene promoters is a hallmark of AML. To define more precisely how cytosine methylation is redistributed in AML, we performed base-pair resolution methylome sequencing in 119 patients. We find that leukemic DNA methylation patterning is tightly linked to somatic mutations and primarily driven by regulatory elements outside of promoters and by CpG shores as opposed to CpG islands. Active enhancers displayed much stronger focal differential methylation than promoters and were generally aberrantly hypomethylated except in IDH2 mutant and CEBPA silenced AMLs...
April 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28405618/efficacy-of-alk5-inhibition-in-myelofibrosis
#9
Lanzhu Yue, Matthias Bartenstein, Wanke Zhao, Wanting Tina Ho, Ying Han, Cem Murdun, Adam W Mailloux, Ling Zhang, Xuefeng Wang, Anjali Budhathoki, Kith Pradhan, Franck Rapaport, Huaquan Wang, Zonghong Shao, Xiubao Ren, Ulrich Steidl, Ross L Levine, Zhizhuang Joe Zhao, Amit Verma, Pearlie K Epling-Burnette
Myelofibrosis (MF) is a bone marrow disorder characterized by clonal myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis, and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in ameliorating MF in patients. TGF-β family members are profibrotic cytokines and we observed significant TGF-β1 isoform overexpression in a large cohort of primary MF patient samples...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28346442/identification-of-12-new-susceptibility-loci-for-different-histotypes-of-epithelial-ovarian-cancer
#10
Catherine M Phelan, Karoline B Kuchenbaecker, Jonathan P Tyrer, Siddhartha P Kar, Kate Lawrenson, Stacey J Winham, Joe Dennis, Ailith Pirie, Marjorie J Riggan, Ganna Chornokur, Madalene A Earp, Paulo C Lyra, Janet M Lee, Simon Coetzee, Jonathan Beesley, Lesley McGuffog, Penny Soucy, Ed Dicks, Andrew Lee, Daniel Barrowdale, Julie Lecarpentier, Goska Leslie, Cora M Aalfs, Katja K H Aben, Marcia Adams, Julian Adlard, Irene L Andrulis, Hoda Anton-Culver, Natalia Antonenkova, Gerasimos Aravantinos, Norbert Arnold, Banu K Arun, Brita Arver, Jacopo Azzollini, Judith Balmaña, Susana N Banerjee, Laure Barjhoux, Rosa B Barkardottir, Yukie Bean, Matthias W Beckmann, Alicia Beeghly-Fadiel, Javier Benitez, Marina Bermisheva, Marcus Q Bernardini, Michael J Birrer, Line Bjorge, Amanda Black, Kenneth Blankstein, Marinus J Blok, Clara Bodelon, Natalia Bogdanova, Anders Bojesen, Bernardo Bonanni, Åke Borg, Angela R Bradbury, James D Brenton, Carole Brewer, Louise Brinton, Per Broberg, Angela Brooks-Wilson, Fiona Bruinsma, Joan Brunet, Bruno Buecher, Ralf Butzow, Saundra S Buys, Trinidad Caldes, Maria A Caligo, Ian Campbell, Rikki Cannioto, Michael E Carney, Terence Cescon, Salina B Chan, Jenny Chang-Claude, Stephen Chanock, Xiao Qing Chen, Yoke-Eng Chiew, Jocelyne Chiquette, Wendy K Chung, Kathleen B M Claes, Thomas Conner, Linda S Cook, Jackie Cook, Daniel W Cramer, Julie M Cunningham, Aimee A D'Aloisio, Mary B Daly, Francesca Damiola, Sakaeva Dina Damirovna, Agnieszka Dansonka-Mieszkowska, Fanny Dao, Rosemarie Davidson, Anna DeFazio, Capucine Delnatte, Kimberly F Doheny, Orland Diez, Yuan Chun Ding, Jennifer Anne Doherty, Susan M Domchek, Cecilia M Dorfling, Thilo Dörk, Laure Dossus, Mercedes Duran, Matthias Dürst, Bernd Dworniczak, Diana Eccles, Todd Edwards, Ros Eeles, Ursula Eilber, Bent Ejlertsen, Arif B Ekici, Steve Ellis, Mingajeva Elvira, Kevin H Eng, Christoph Engel, D Gareth Evans, Peter A Fasching, Sarah Ferguson, Sandra Fert Ferrer, James M Flanagan, Zachary C Fogarty, Renée T Fortner, Florentia Fostira, William D Foulkes, George Fountzilas, Brooke L Fridley, Tara M Friebel, Eitan Friedman, Debra Frost, Patricia A Ganz, Judy Garber, María J García, Vanesa Garcia-Barberan, Andrea Gehrig, Aleksandra Gentry-Maharaj, Anne-Marie Gerdes, Graham G Giles, Rosalind Glasspool, Gord Glendon, Andrew K Godwin, David E Goldgar, Teodora Goranova, Martin Gore, Mark H Greene, Jacek Gronwald, Stephen Gruber, Eric Hahnen, Christopher A Haiman, Niclas Håkansson, Ute Hamann, Thomas V O Hansen, Patricia A Harrington, Holly R Harris, Jan Hauke, Alexander Hein, Alex Henderson, Michelle A T Hildebrandt, Peter Hillemanns, Shirley Hodgson, Claus K Høgdall, Estrid Høgdall, Frans B L Hogervorst, Helene Holland, Maartje J Hooning, Karen Hosking, Ruea-Yea Huang, Peter J Hulick, Jillian Hung, David J Hunter, David G Huntsman, Tomasz Huzarski, Evgeny N Imyanitov, Claudine Isaacs, Edwin S Iversen, Louise Izatt, Angel Izquierdo, Anna Jakubowska, Paul James, Ramunas Janavicius, Mats Jernetz, Allan Jensen, Uffe Birk Jensen, Esther M John, Sharon Johnatty, Michael E Jones, Päivi Kannisto, Beth Y Karlan, Anthony Karnezis, Karin Kast, Catherine J Kennedy, Elza Khusnutdinova, Lambertus A Kiemeney, Johanna I Kiiski, Sung-Won Kim, Susanne K Kjaer, Martin Köbel, Reidun K Kopperud, Torben A Kruse, Jolanta Kupryjanczyk, Ava Kwong, Yael Laitman, Diether Lambrechts, Nerea Larrañaga, Melissa C Larson, Conxi Lazaro, Nhu D Le, Loic Le Marchand, Jong Won Lee, Shashikant B Lele, Arto Leminen, Dominique Leroux, Jenny Lester, Fabienne Lesueur, Douglas A Levine, Dong Liang, Clemens Liebrich, Jenna Lilyquist, Loren Lipworth, Jolanta Lissowska, Karen H Lu, Jan Lubinński, Craig Luccarini, Lene Lundvall, Phuong L Mai, Gustavo Mendoza-Fandiño, Siranoush Manoukian, Leon F A G Massuger, Taymaa May, Sylvie Mazoyer, Jessica N McAlpine, Valerie McGuire, John R McLaughlin, Iain McNeish, Hanne Meijers-Heijboer, Alfons Meindl, Usha Menon, Arjen R Mensenkamp, Melissa A Merritt, Roger L Milne, Gillian Mitchell, Francesmary Modugno, Joanna Moes-Sosnowska, Melissa Moffitt, Marco Montagna, Kirsten B Moysich, Anna Marie Mulligan, Jacob Musinsky, Katherine L Nathanson, Lotte Nedergaard, Roberta B Ness, Susan L Neuhausen, Heli Nevanlinna, Dieter Niederacher, Robert L Nussbaum, Kunle Odunsi, Edith Olah, Olufunmilayo I Olopade, Håkan Olsson, Curtis Olswold, David M O'Malley, Kai-Ren Ong, N Charlotte Onland-Moret, Nicholas Orr, Sandra Orsulic, Ana Osorio, Domenico Palli, Laura Papi, Tjoung-Won Park-Simon, James Paul, Celeste L Pearce, Inge Søkilde Pedersen, Petra H M Peeters, Bernard Peissel, Ana Peixoto, Tanja Pejovic, Liisa M Pelttari, Jennifer B Permuth, Paolo Peterlongo, Lidia Pezzani, Georg Pfeiler, Kelly-Anne Phillips, Marion Piedmonte, Malcolm C Pike, Anna M Piskorz, Samantha R Poblete, Timea Pocza, Elizabeth M Poole, Bruce Poppe, Mary E Porteous, Fabienne Prieur, Darya Prokofyeva, Elizabeth Pugh, Miquel Angel Pujana, Pascal Pujol, Paolo Radice, Johanna Rantala, Christine Rappaport-Fuerhauser, Gad Rennert, Kerstin Rhiem, Patricia Rice, Andrea Richardson, Mark Robson, Gustavo C Rodriguez, Cristina Rodríguez-Antona, Jane Romm, Matti A Rookus, Mary Anne Rossing, Joseph H Rothstein, Anja Rudolph, Ingo B Runnebaum, Helga B Salvesen, Dale P Sandler, Minouk J Schoemaker, Leigha Senter, V Wendy Setiawan, Gianluca Severi, Priyanka Sharma, Tameka Shelford, Nadeem Siddiqui, Lucy E Side, Weiva Sieh, Christian F Singer, Hagay Sobol, Honglin Song, Melissa C Southey, Amanda B Spurdle, Zsofia Stadler, Doris Steinemann, Dominique Stoppa-Lyonnet, Lara E Sucheston-Campbell, Grzegorz Sukiennicki, Rebecca Sutphen, Christian Sutter, Anthony J Swerdlow, Csilla I Szabo, Lukasz Szafron, Yen Y Tan, Jack A Taylor, Muy-Kheng Tea, Manuel R Teixeira, Soo-Hwang Teo, Kathryn L Terry, Pamela J Thompson, Liv Cecilie Vestrheim Thomsen, Darcy L Thull, Laima Tihomirova, Anna V Tinker, Marc Tischkowitz, Silvia Tognazzo, Amanda Ewart Toland, Alicia Tone, Britton Trabert, Ruth C Travis, Antonia Trichopoulou, Nadine Tung, Shelley S Tworoger, Anne M van Altena, David Van Den Berg, Annemarie H van der Hout, Rob B van der Luijt, Mattias Van Heetvelde, Els Van Nieuwenhuysen, Elizabeth J van Rensburg, Adriaan Vanderstichele, Raymonda Varon-Mateeva, Ana Vega, Digna Velez Edwards, Ignace Vergote, Robert A Vierkant, Joseph Vijai, Athanassios Vratimos, Lisa Walker, Christine Walsh, Dorothea Wand, Shan Wang-Gohrke, Barbara Wappenschmidt, Penelope M Webb, Clarice R Weinberg, Jeffrey N Weitzel, Nicolas Wentzensen, Alice S Whittemore, Juul T Wijnen, Lynne R Wilkens, Alicja Wolk, Michelle Woo, Xifeng Wu, Anna H Wu, Hannah Yang, Drakoulis Yannoukakos, Argyrios Ziogas, Kristin K Zorn, Steven A Narod, Douglas F Easton, Christopher I Amos, Joellen M Schildkraut, Susan J Ramus, Laura Ottini, Marc T Goodman, Sue K Park, Linda E Kelemen, Harvey A Risch, Mads Thomassen, Kenneth Offit, Jacques Simard, Rita Katharina Schmutzler, Dennis Hazelett, Alvaro N Monteiro, Fergus J Couch, Andrew Berchuck, Georgia Chenevix-Trench, Ellen L Goode, Thomas A Sellers, Simon A Gayther, Antonis C Antoniou, Paul D P Pharoah
To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC...
May 2017: Nature Genetics
https://www.readbyqxmd.com/read/28315400/multicolor-flow-cytometry-and-multigene-next-generation-sequencing-are-complementary-and-highly-predictive-for-relapse-in-acute-myeloid-leukemia-after-allogeneic-transplantation
#11
Bartlomiej M Getta, Sean M Devlin, Ross L Levine, Maria E Arcila, Abhinita S Mohanty, Ahmet Zehir, Martin S Tallman, Sergio A Giralt, Mikhail Roshal
Minimal residual disease (MRD) in acute myeloid leukemia (AML) is typically measured using multiparameter flow cytometry (MFC). Detection of leukemia mutations using multigene next-generation sequencing (NGS) can potentially be used to measure residual disease. We used a targeted 28-gene NGS panel to detect mutations and different-from-normal 10-color MFC to measure MRD in AML patients before allogeneic hematopoietic stem cell transplantation (HCT). Residual disease was defined when any abnormal blast population was detected using MFC and when any leukemia allele was detected with a variant allele frequency (VAF)  ≥ 5% using NGS...
March 15, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28277735/the-core-symptoms-of-bulimia-nervosa-anxiety-and-depression-a-network-analysis
#12
Cheri A Levinson, Stephanie Zerwas, Benjamin Calebs, Kelsie Forbush, Hans Kordy, Hunna Watson, Sara Hofmeier, Michele Levine, Ross D Crosby, Christine Peat, Cristin D Runfola, Benjamin Zimmer, Markus Moesner, Marsha D Marcus, Cynthia M Bulik
Bulimia nervosa (BN) is characterized by symptoms of binge eating and compensatory behavior, and overevaluation of weight and shape, which often co-occur with symptoms of anxiety and depression. However, there is little research identifying which specific BN symptoms maintain BN psychopathology and how they are associated with symptoms of depression and anxiety. Network analyses represent an emerging method in psychopathology research to examine how symptoms interact and may become self-reinforcing. In the current study of adults with a Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition (DSM-IV) diagnosis of BN (N = 196), we used network analysis to identify the central symptoms of BN, as well as symptoms that may bridge the association between BN symptoms and anxiety and depression symptoms...
April 2017: Journal of Abnormal Psychology
https://www.readbyqxmd.com/read/28242787/tet2-in-normal-and-malignant-hematopoiesis
#13
Robert L Bowman, Ross L Levine
The ten-eleven translocation (TET) family of enzymes were originally cloned from the translocation breakpoint of t(10;11) in infant acute myeloid leukemia (AML) with subsequent genomic analyses revealing somatic mutations and suppressed expression of TET family members across a range of malignancies, particularly enriched in hematological neoplasms. The TET family of enzymes is responsible for the hydroxylation of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), followed by active and passive mechanisms leading to DNA demethylation...
February 27, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28225756/cardiovascular-disease-commonality-with-cancer
#14
COMMENT
Alan R Tall, Ross L Levine
No abstract text is available yet for this article.
March 2, 2017: Nature
https://www.readbyqxmd.com/read/28193779/combination-targeted-therapy-to-disrupt-aberrant-oncogenic-signaling-and-reverse-epigenetic-dysfunction-in-idh2-and-tet2-mutant-acute-myeloid-leukemia
#15
Alan H Shih, Cem Meydan, Kaitlyn Shank, Francine E Garrett-Bakelman, Patrick S Ward, Andrew M Intlekofer, Abbas Nazir, Eytan M Stein, Kristina Knapp, Jacob Glass, Jeremy Travins, Kim Straley, Camelia Gliser, Christopher E Mason, Katharine Yen, Craig B Thompson, Ari Melnick, Ross L Levine
Genomic studies in acute myeloid leukemias (AML) have identified mutations that drive altered DNA methylation, including TET2 and IDH2 Here, we show that models of AML resulting from TET2 or IDH2 mutations combined with FLT3(ITD) mutations are sensitive to 5-azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-azacytidine and AG-221 treatment induced an attenuation of aberrant DNA methylation and transcriptional output and resulted in a reduction in leukemic blasts consistent with antileukemic activity...
May 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28135282/mesenchymal-cell-reprogramming-in-experimental-mplw515l-mouse-model-of-myelofibrosis
#16
Ying Han, Lanzhu Yue, Max Wei, Xiubao Ren, Zonghong Shao, Ling Zhang, Ross L Levine, Pearlie K Epling-Burnette
Myelofibrosis is an indicator of poor prognosis in myeloproliferative neoplasms (MPNs), but the precise mechanism(s) contributing to extracellular matrix remodeling and collagen deposition in the bone marrow (BM) niche remains unanswered. In this study, we isolated mesenchymal stromal cells (MSCs) from mice transplanted with wild-type thrombopoietin receptor (MPLWT) and MPLW515L retroviral-transduced bone marrow. Using MSCs derived from MPLW515-transplant recipients, excessive collagen deposition was maintained in the absence of the virus and neoplastic hematopoietic cells suggested that the MSCs were reprogrammed in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28123069/cd99-is-a-therapeutic-target-on-disease-stem-cells-in-myeloid-malignancies
#17
Stephen S Chung, William S Eng, Wenhuo Hu, Mona Khalaj, Francine E Garrett-Bakelman, Montreh Tavakkoli, Ross L Levine, Martin Carroll, Virginia M Klimek, Ari M Melnick, Christopher Y Park
Acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS) are initiated and sustained by self-renewing malignant stem cells; thus, eradication of AML and MDS stem cells is required for cure. We identified CD99 as a cell surface protein frequently overexpressed on AML and MDS stem cells. Expression of CD99 allows for prospective separation of leukemic stem cells (LSCs) from functionally normal hematopoietic stem cells in AML, and high CD99 expression on AML blasts enriches for functional LSCs as demonstrated by limiting dilution xenotransplant studies...
January 25, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28103614/enrichment-of-putative-pax8-target-genes-at-serous-epithelial-ovarian-cancer-susceptibility-loci
#18
Siddhartha P Kar, Emily Adler, Jonathan Tyrer, Dennis Hazelett, Hoda Anton-Culver, Elisa V Bandera, Matthias W Beckmann, Andrew Berchuck, Natalia Bogdanova, Louise Brinton, Ralf Butzow, Ian Campbell, Karen Carty, Jenny Chang-Claude, Linda S Cook, Daniel W Cramer, Julie M Cunningham, Agnieszka Dansonka-Mieszkowska, Jennifer Anne Doherty, Thilo Dörk, Matthias Dürst, Diana Eccles, Peter A Fasching, James Flanagan, Aleksandra Gentry-Maharaj, Rosalind Glasspool, Ellen L Goode, Marc T Goodman, Jacek Gronwald, Florian Heitz, Michelle A T Hildebrandt, Estrid Høgdall, Claus K Høgdall, David G Huntsman, Allan Jensen, Beth Y Karlan, Linda E Kelemen, Lambertus A Kiemeney, Susanne K Kjaer, Jolanta Kupryjanczyk, Diether Lambrechts, Douglas A Levine, Qiyuan Li, Jolanta Lissowska, Karen H Lu, Jan Lubiński, Leon F A G Massuger, Valerie McGuire, Iain McNeish, Usha Menon, Francesmary Modugno, Alvaro N Monteiro, Kirsten B Moysich, Roberta B Ness, Heli Nevanlinna, James Paul, Celeste L Pearce, Tanja Pejovic, Jennifer B Permuth, Catherine Phelan, Malcolm C Pike, Elizabeth M Poole, Susan J Ramus, Harvey A Risch, Mary Anne Rossing, Helga B Salvesen, Joellen M Schildkraut, Thomas A Sellers, Mark Sherman, Nadeem Siddiqui, Weiva Sieh, Honglin Song, Melissa Southey, Kathryn L Terry, Shelley S Tworoger, Christine Walsh, Nicolas Wentzensen, Alice S Whittemore, Anna H Wu, Hannah Yang, Wei Zheng, Argyrios Ziogas, Matthew L Freedman, Simon A Gayther, Paul D P Pharoah, Kate Lawrenson
BACKGROUND: Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis. METHODS: All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery), and combined (9627 cases/30 845 controls; including additional individuals)...
February 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28078910/gain-of-chromosome-1q-portends-worse-prognosis-in-multiple-myeloma-despite-novel-agent-based-induction-regimens-and-autologous-transplantation
#19
Gunjan L Shah, Heather Landau, Dory Londono, Sean M Devlin, Satyajit Kosuri, Alexander M Lesokhin, Nikoletta Lendvai, Hani Hassoun, David J Chung, Guenther Koehne, Suresh C Jhanwar, Ola Landgren, Ross Levine, Sergio A Giralt
We aimed to identify whether the use of autologous hematopoietic cell transplantation (HCT) impacts outcomes for multiple myeloma patients with gains of chromosome 1q (+1q). We retrospectively identified 95 patients, 21% having +1q. For patients with +1q, the overall response rate to induction was 85%, with 40% having ≥ VGPR and 20% achieving a CR, similar to non +1q patients (p = .64). The median PFS from diagnosis with +1q was 2.1 years (95% CI: 1.2-not reached (NR)) vs 4.3 years (95% CI: 3...
August 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28077417/aid-is-a-key-regulator-of-myeloid-erythroid-differentiation-and-dna-methylation-in-hematopoietic-stem-progenitor-cells
#20
Hiroyoshi Kunimoto, Anna Sophia McKenney, Cem Meydan, Kaitlyn Shank, Abbas Nazir, Franck Rapaport, Benjamin Durham, Francine E Garrett-Bakelman, Elodie Pronier, Alan H Shih, Ari Melnick, Jayanta Chaudhuri, Ross L Levine
Recent studies have reported that activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members regulate active DNA demethylation. Genetic alterations of TET2 occur in myeloid malignancies, and hematopoietic-specific loss of Tet2 induces aberrant hematopoietic stem cell (HSC) self-renewal/differentiation, implicating TET2 as a master regulator of normal and malignant hematopoiesis. Despite the functional link between AID and TET in epigenetic gene regulation, the role of AID loss in hematopoiesis and myeloid transformation remains to be investigated...
March 30, 2017: Blood
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