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Aaron D. Viny

Aaron D Viny, Ross L Levine
PURPOSE OF REVIEW: Recurrent loss of function mutations within genes of the cohesin complex have been identified in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). STAG2 is the most commonly mutated cohesin member in AML as well as solid tumors. STAG2 is recurrently, mutated in Ewing's Sarcoma, bladder cancer, and glioblastoma, and is one of only ten genes known to be recurrently mutated in over four distinct tissue types of human cancer RECENT FINDINGS: The cohesin complex, a multiprotein ring, is canonically known to align and stabilize replicated chromosomes prior to cell division...
March 2018: Current Opinion in Hematology
Justine M Kahn, Theresa H M Keegan, Li Tao, Renata Abrahão, Archie Bleyer, Aaron D Viny
BACKGROUND: Race-based survival in children and adolescents with hematologic malignancies has been a national challenge for decades. Large-scale investigations of age- and race-based survival trends over time in these patients have not previously been reported. The objective of this study was to investigate whether race- and age-related differences in pediatric and adolescent and young adult (AYA) leukemia and lymphoma survival persist and to what extent these differences have changed over time...
September 1, 2016: Cancer
Aaron D Viny, Ross L Levine
No abstract text is available yet for this article.
June 9, 2016: New England Journal of Medicine
Nicole Kucine, Aaron D Viny, Raajit Rampal, Michael Berger, Nicholas Socci, Agnes Viale, James B Bussel, Ross L Levine, Franck Rapaport
No abstract text is available yet for this article.
June 2016: Haematologica
Peter van Galen, Aaron D Viny, Oren Ram, Russell J H Ryan, Matthew J Cotton, Laura Donohue, Cem Sievers, Yotam Drier, Brian B Liau, Shawn M Gillespie, Kaitlin M Carroll, Michael B Cross, Ross L Levine, Bradley E Bernstein
Genome-wide profiling of histone modifications can provide systematic insight into the regulatory elements and programs engaged in a given cell type. However, conventional chromatin immunoprecipitation and sequencing (ChIP-seq) does not capture quantitative information on histone modification levels, requires large amounts of starting material, and involves tedious processing of each individual sample. Here, we address these limitations with a technology that leverages DNA barcoding to profile chromatin quantitatively and in multiplexed format...
January 7, 2016: Molecular Cell
Daneng Li, Ghassan K Abou-Alfa, Aaron D Viny, Meredith Cammarata, Ali Shamseddine, Ashwaq Al-Olayan, Hibah Osman, Ali Haydar, Ghassan Kanazi, Mohamed Naghy, Eileen M O'Reilly, Andrew S Epstein
No abstract text is available yet for this article.
October 2015: Journal of Gastrointestinal Oncology
Aaron D Viny, Christopher J Ott, Barbara Spitzer, Martin Rivas, Cem Meydan, Efthymia Papalexi, Dana Yelin, Kaitlyn Shank, Jaime Reyes, April Chiu, Yevgeniy Romin, Vitaly Boyko, Swapna Thota, Jaroslaw P Maciejewski, Ari Melnick, James E Bradner, Ross L Levine
Cohesin complex members have recently been identified as putative tumor suppressors in hematologic and epithelial malignancies. The cohesin complex guides chromosome segregation; however, cohesin mutant leukemias do not show genomic instability. We hypothesized that reduced cohesin function alters chromatin structure and disrupts cis-regulatory architecture of hematopoietic progenitors. We investigated the consequences of Smc3 deletion in normal and malignant hematopoiesis. Biallelic Smc3 loss induced bone marrow aplasia with premature sister chromatid separation and revealed an absolute requirement for cohesin in hematopoietic stem cell (HSC) function...
October 19, 2015: Journal of Experimental Medicine
Swapna Thota, Aaron D Viny, Hideki Makishima, Barbara Spitzer, Tomas Radivoyevitch, Bartlomiej Przychodzen, Mikkael A Sekeres, Ross L Levine, Jaroslaw P Maciejewski
Somatic cohesin mutations have been reported in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). To account for the morphologic and cytogenetic diversity of these neoplasms, a well-annotated cohort of 1060 patients with myeloid malignancies including MDS (n = 386), myeloproliferative neoplasms (MPNs) (n = 55), MDS/MPNs (n = 169), and AML (n = 450) were analyzed for cohesin gene mutational status, gene expression, and therapeutic and survival outcomes. Somatic cohesin defects were detected in 12% of patients with myeloid malignancies, whereas low expression of these genes was present in an additional 15% of patients...
September 11, 2014: Blood
Aaron D Viny, Ross L Levine
In the last decade, genomic studies have identified multiple recurrent somatic mutations in myeloproliferative neoplasms (MPNs). Beginning with the discovery of the JAK2 V617F mutation, multiple additional mutations have been found that constitutively activate cell-signaling pathways, including MPL, CBL, and LNK. Furthermore, several classes of epigenetic modifiers have also been identified, in patients with MPN, revealing a requirement for mutations in other pathways to cooperate with JAK-STAT pathway mutations in MPN pathogenesis...
January 2014: Cancer Journal
Betty C Chen, Aaron D Viny, Fiona M Garlich, Paul Basciano, Mary Ann Howland, Silas W Smith, Robert S Hoffman, Lewis S Nelson
OBJECTIVE: Dabigatran is a direct thrombin inhibitor approved for anticoagulation in non-valvular atrial fibrillation and, in some countries, for thromboembolism prophylaxis following select orthopedic surgeries. Despite decreased rates of thromboembolism, bleeding remains a risk due to the inability to conveniently monitor anticoagulant effect and the lack of a reversal agent. CASE SERIES: We present four cases of dabigatran-related bleeding. A 79-year-old man on aspirin, clopidogrel, and dabigatran presented with rectal bleeding and epistaxis...
November 2012: Clinical Toxicology
Michael J Clemente, Marcin W Wlodarski, Hideki Makishima, Aaron D Viny, Isabell Bretschneider, Mohammad Shaik, Nelli Bejanyan, Alan E Lichtin, Eric D Hsi, Eric D His, Ronald L Paquette, Thomas P Loughran, Jaroslaw P Maciejewski
T-cell large granular lymphocyte leukemia (T-LGLL) is characterized by chronic lymphoproliferation of cytotoxic T lymphocytes (CTLs) and is associated with lineage-restricted cytopenias. Introduction of T-cell receptor (TCR) variable β-chain (Vβ) monoclonal antibodies has facilitated identification and enumeration of clonal CTLs by flow cytometry. A highly skewed TCR Vβ repertoire identified by flow cytometry is strongly associated with monoclonal CDR3 regions by quantitative sequencing and positive TCRγ rearrangement assays...
October 20, 2011: Blood
Aaron D Viny, Michael J Clemente, Monika Jasek, Medhat Askar, Hemant Ishwaran, Amy Nowacki, Aiwen Zhang, Jaroslaw P Maciejewski
BACKGROUND: Large granular lymphocyte leukemia is a semi-autonomous clonal proliferation of cytotoxic T cells accompanied by immune cytopenias and various autoimmune conditions. Due to the rarity of this disease and its association with autoimmune diseases, a theoretical germline or somatic mutation might have significant penetrance, thus enabling detection, even from samples of suboptimal size, through genome-wide association studies. DESIGN AND METHODS: To investigate a non-mendelian genetic predisposition to large granular lymphocyte leukemia, we used a step-wise method for gene discovery...
October 2010: Haematologica
Vivek Subbiah, Aaron D Viny, Steven Rosenblatt, Brad Pohlman, Alan Lichtin, Jaroslaw P Maciejewski
OBJECTIVE: T-cell large granular lymphocyte leukemia (T-LGL) is a chronic clonal lymphoproliferation of cytotoxic T cells often complicated by cytopenia. Because the outcomes of splenectomy in patients with T-LGL have been only reported sporadically, we objectively assessed the outcomes of splenectomy. MATERIALS AND METHODS: When a cohort of 56 T-LGL patients was analyzed, patients with splenomegaly (n = 34) and had higher frequency of bi- and pancytopenia than patients with no splenomegaly (70% vs 27%; p = 0...
September 2008: Experimental Hematology
Aaron D Viny, Alan Lichtin, Brad Pohlman, Thomas Loughran, Jaroslaw Maciejewski
T cell large granular lymphocyte leukemia (T-LGL) is characterised by semiautonomous proliferation of monoclonal cytotoxic T lymphocytes, which can result in neutropenia, splenomegaly, and is associated with various autoimmune disorders, particularly rheumatoid arthritis. The coexistence of T-LGL leukemia with B cell abnormalities has previously been identified in case reports. However, no systematic analysis to determine the frequency of this co-association has been reported. Analysis of 63 T-LGL patients revealed a frequent association with humoral immune system abnormalities...
May 2008: Leukemia & Lymphoma
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