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Omar Abdel-Wahab

Sydney X Lu, Omar Abdel-Wahab
No abstract text is available yet for this article.
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Daichi Inoue, Omar Abdel-Wahab
In this issue of Cancer Cell, Obeng et al. identify the consequences of expressing the most common mutation in the spliceosomal gene SF3B1 on hematopoiesis. The knockin mouse model described represents a valuable tool to dissect the effects of SF3B1 mutations on transformation, splicing, and less well-characterized functions of SF3B1.
September 12, 2016: Cancer Cell
Stanley Chun-Wei Lee, Omar Abdel-Wahab
Recent studies have highlighted that splicing patterns are frequently altered in cancer and that mutations in genes encoding spliceosomal proteins, as well as mutations affecting the splicing of key cancer-associated genes, are enriched in cancer. In parallel, there is also accumulating evidence that several molecular subtypes of cancer are highly dependent on splicing function for cell survival. These findings have resulted in a growing interest in targeting splicing catalysis, splicing regulatory proteins, and/or specific key altered splicing events in the treatment of cancer...
September 7, 2016: Nature Medicine
Akihide Yoshimi, Omar Abdel-Wahab
No abstract text is available yet for this article.
August 18, 2016: Blood
Eli L Diamond, Omar Abdel-Wahab, Benjamin H Durham, Ahmet Dogan, Neval Ozkaya, Lynn Brody, Maria Arcila, Christian Bowers, Mark Fluchel
No abstract text is available yet for this article.
August 17, 2016: Blood
Jean-Baptiste Micol, Omar Abdel-Wahab
Additional sex combs-like (ASXL) proteins are mammalian homologs of Addition of sex combs (Asx), a protein that regulates the balance of trithorax and Polycomb function in Drosophila. All three ASXL family members (ASXL1, ASXL2, and ASXL3) are affected by somatic or de novo germline mutations in cancer or rare developmental syndromes, respectively. Although Asx is characterized as a catalytic partner for the deubiquitinase Calypso (or BAP1), there are domains of ASXL proteins that are distinct from Asx and the roles and redundancies of ASXL members are not yet well understood...
October 3, 2016: Cold Spring Harbor Perspectives in Medicine
Mahmoud Abdelwahab Ali, Mohamed Morsi Elshobari, Tarek Salah, Al-Refaey Kandeel, Ahmad Mohammad Sultan, Ahmad Nabieh Elghawalby, Ahmed Shehta, Usama Elsayed, Omar Fathy, Amr Yassen, Mohamed Abdel Wahab
Introduction Living donor liver transplantation (LDLT) is a valuable option for expanding donor pool, especially in localities where deceased organ harvesting is not allowed. In addition, rejection rates were found to be lower in LDLT, which is attributed to the fact that LDLT is usually performed between relatives. However, the impact of genetic relation on the outcome of LDLT hasn't been studied. In this study, we examined the difference in rejection rates between LDLT from genetically related (GR) donors and genetically unrelated (GUR) donors...
August 12, 2016: Liver Transplantation
Wendy Béguelin, Matt Teater, Micah D Gearhart, María Teresa Calvo Fernández, Rebecca L Goldstein, Mariano G Cárdenas, Katerina Hatzi, Monica Rosen, Hao Shen, Connie M Corcoran, Michelle Y Hamline, Randy D Gascoyne, Ross L Levine, Omar Abdel-Wahab, Jonathan D Licht, Rita Shaknovich, Olivier Elemento, Vivian J Bardwell, Ari M Melnick
The EZH2 histone methyltransferase mediates the humoral immune response and drives lymphomagenesis through formation of bivalent chromatin domains at critical germinal center (GC) B cell promoters. Herein we show that the actions of EZH2 in driving GC formation and lymphoma precursor lesions require site-specific binding by the BCL6 transcriptional repressor and the presence of a non-canonical PRC1-BCOR-CBX8 complex. The chromodomain protein CBX8 is induced in GC B cells, binds to H3K27me3 at bivalent promoters, and is required for stable association of the complex and the resulting histone modifications...
August 8, 2016: Cancer Cell
Panagiotis Ntziachristos, Omar Abdel-Wahab, Iannis Aifantis
The past decade brought a revolution in understanding of the structure, topology and disease-inducing lesions of RNA and DNA, fueled by unprecedented progress in next-generation sequencing. This technological revolution has also affected understanding of the epigenome and has provided unique opportunities for the analysis of DNA and histone modifications, as well as the first map of the non-protein-coding genome and three-dimensional (3D) chromosomal interactions. Overall, these advances have facilitated studies that combine genetic, transcriptomics and epigenomics data to address a wide range of issues ranging from understanding the role of the epigenome in development to targeting the transcription of noncoding genes in human cancer...
September 2016: Nature Immunology
Hui Shi, Shohei Yamamoto, Mengyao Sheng, Jie Bai, Peng Zhang, Runze Chen, Shi Chen, Lihong Shi, Omar Abdel-Wahab, Mingjiang Xu, Yuan Zhou, Feng-Chun Yang
ASXL1 mutations are found in a spectrum of myeloid malignancies with poor prognosis. Recently, we reported that Asxl1(+/-) mice develop myelodysplastic syndrome (MDS) or MDS and myeloproliferative neoplasms (MPN) overlapping diseases (MDS/MPN). Although defective erythroid maturation and anemia are associated with the prognosis of patients with MDS or MDS/MPN, the role of ASXL1 in erythropoiesis remains unclear. Here, we showed that chronic myelomonocytic leukemia (CMML) patients with ASXL1 mutations exhibited more severe anemia with a significantly increased proportion of bone marrow (BM) early stage erythroblasts and reduced enucleated erythrocytes compared to CMML patients with WT ASXL1...
2016: Scientific Reports
Bartlomiej M Getta, Kaitlin M Woo, Sean Devlin, Jae H Park, Omar Abdel-Wahab, Alan Saven, Kanti Rai, Martin S Tallman
Repeated therapy of hairy cell leukaemia (HCL) with treatments that have potential long-term toxicities has raised concerns regarding increased risk for younger patients. We compared clinical outcomes and disease complications in 63 patients with HCL aged ≤40 years at diagnosis with 268 patients >40 years treated at Memorial Sloan Kettering Cancer Center. The rate of complete remission following initial therapy was 87% and 83% (P = 0·71) and estimated 10-year overall survival was 100% and 82% (P = 0·25) in younger and older patients, respectively...
June 28, 2016: British Journal of Haematology
Rui Lu, Ping Wang, Trevor Parton, Yang Zhou, Kaliopi Chrysovergis, Shira Rockowitz, Wei-Yi Chen, Omar Abdel-Wahab, Paul A Wade, Deyou Zheng, Gang Greg Wang
DNA methyltransferase 3A (DNMT3A) is frequently mutated in hematological cancers; however, the underlying oncogenic mechanism remains elusive. Here, we report that the DNMT3A mutational hotspot at Arg882 (DNMT3A(R882H)) cooperates with NRAS mutation to transform hematopoietic stem/progenitor cells and induce acute leukemia development. Mechanistically, DNMT3A(R882H) directly binds to and potentiates transactivation of stemness genes critical for leukemogenicity including Meis1, Mn1, and Hoxa gene cluster. DNMT3A(R882H) induces focal epigenetic alterations, including CpG hypomethylation and concurrent gain of active histone modifications, at cis-regulatory elements such as enhancers to facilitate gene transcription...
July 11, 2016: Cancer Cell
Heidi Dvinge, Eunhee Kim, Omar Abdel-Wahab, Robert K Bradley
The recent genomic characterization of cancers has revealed recurrent somatic point mutations and copy number changes affecting genes encoding RNA splicing factors. Initial studies of these 'spliceosomal mutations' suggest that the proteins bearing these mutations exhibit altered splice site and/or exon recognition preferences relative to their wild-type counterparts, resulting in cancer-specific mis-splicing. Such changes in the splicing machinery may create novel vulnerabilities in cancer cells that can be therapeutically exploited using compounds that can influence the splicing process...
July 2016: Nature Reviews. Cancer
Stanley Chun-Wei Lee, Heidi Dvinge, Eunhee Kim, Hana Cho, Jean-Baptiste Micol, Young Rock Chung, Benjamin H Durham, Akihide Yoshimi, Young Joon Kim, Michael Thomas, Camille Lobry, Chun-Wei Chen, Alessandro Pastore, Justin Taylor, Xujun Wang, Andrei Krivtsov, Scott A Armstrong, James Palacino, Silvia Buonamici, Peter G Smith, Robert K Bradley, Omar Abdel-Wahab
No abstract text is available yet for this article.
June 7, 2016: Nature Medicine
Lindsay M LaFave, Wendy Béguelin, Richard Koche, Matt Teater, Barbara Spitzer, Alan Chramiec, Efthymia Papalexi, Matthew D Keller, Todd Hricik, Katerina Konstantinoff, Jean-Baptiste Micol, Benjamin Durham, Sarah K Knutson, John E Campbell, Gil Blum, Xinxu Shi, Emma H Doud, Andrei V Krivtsov, Young Rock Chung, Inna Khodos, Elisa de Stanchina, Ouathek Ouerfelli, Prasad S Adusumilli, Paul M Thomas, Neil L Kelleher, Minkui Luo, Heike Keilhack, Omar Abdel-Wahab, Ari Melnick, Scott A Armstrong, Ross L Levine
No abstract text is available yet for this article.
June 7, 2016: Nature Medicine
Tariq I Mughal, Omar Abdel-Wahab, Raajit Rampal, Ruben Mesa, Steffen Koschmieder, Ross Levine, Rüdiger Hehlmann, Giuseppe Saglio, Tiziano Barbui, Richard A Van Etten
This review is based on the deliberations at the 5th John Goldman Colloquium held in Estoril on 2nd October 2015 and the 9th post-ASH International Workshop on chronic myeloid leukemia (CML) and BCR-ABL1-negative myeloproliferative neoplasms (MPN) which took place on the 10th-11th December 2014, immediately following the 56th American Society of Hematology Annual Meeting. It has been updated since and summarizes the most recent advances in the biology and therapy of these diseases, in particular updates of genetics of MPN, novel insights from mouse MPN models, targeting CML stem cells and its niche; clinical advances include updates on JAK2 inhibitors and other therapeutic approaches to BCR-ABL1-negative MPNs, the use of alpha interferons, updates on tyrosine kinase inhibitors (TKI) randomized trials in CML, TKI cessation studies, and optimal monitoring strategies...
July 2016: Leukemia & Lymphoma
Peng Zhang, Caihong Xing, Steven D Rhodes, Yongzheng He, Kai Deng, Zhaomin Li, Fuhong He, Caiying Zhu, Lihn Nguyen, Yuan Zhou, Shi Chen, Khalid S Mohammad, Theresa A Guise, Omar Abdel-Wahab, Mingjiang Xu, Qian-Fei Wang, Feng-Chun Yang
De novo ASXL1 mutations are found in patients with Bohring-Opitz syndrome, a disease with severe developmental defects and early childhood mortality. The underlying pathologic mechanisms remain largely unknown. Using Asxl1-targeted murine models, we found that Asxl1 global loss as well as conditional deletion in osteoblasts and their progenitors led to significant bone loss and a markedly decreased number of bone marrow stromal cells (BMSCs) compared with wild-type littermates. Asxl1(-/-) BMSCs displayed impaired self-renewal and skewed differentiation, away from osteoblasts and favoring adipocytes...
June 14, 2016: Stem Cell Reports
Daichi Inoue, Robert K Bradley, Omar Abdel-Wahab
Genomic analyses of the myeloid malignancies and clonal disorders of hematopoiesis that may give rise to these disorders have identified that mutations in genes encoding core spliceosomal proteins and accessory regulatory splicing factors are among the most common targets of somatic mutations. These spliceosomal mutations often occur in a mutually exclusive manner with one another and, in aggregate, account for the most frequent class of mutations in patients with myelodysplastic syndromes (MDSs) in particular...
May 1, 2016: Genes & Development
Stanley Chun-Wei Lee, Heidi Dvinge, Eunhee Kim, Hana Cho, Jean-Baptiste Micol, Young Rock Chung, Benjamin H Durham, Akihide Yoshimi, Young Joon Kim, Michael Thomas, Camille Lobry, Chun-Wei Chen, Alessandro Pastore, Justin Taylor, Xujun Wang, Andrei Krivtsov, Scott A Armstrong, James Palacino, Silvia Buonamici, Peter G Smith, Robert K Bradley, Omar Abdel-Wahab
Mutations in genes encoding splicing factors (which we refer to as spliceosomal genes) are commonly found in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These mutations recurrently affect specific amino acid residues, leading to perturbed normal splice site and exon recognition. Spliceosomal gene mutations are always heterozygous and rarely occur together with one another, suggesting that cells may tolerate only a partial deviation from normal splicing activity. To test this hypothesis, we engineered mice to express a mutated allele of serine/arginine-rich splicing factor 2 (Srsf2(P95H))-which commonly occurs in individuals with MDS and AML-in an inducible, hemizygous manner in hematopoietic cells...
June 2016: Nature Medicine
Benjamin H Durham, Eli L Diamond, Omar Abdel-Wahab
PURPOSE OF REVIEW: Since the discovery of B-Raf proto-oncogene (BRAF) V600E mutations in histiocytic neoplasms, diverse kinase alterations have been uncovered in BRAF V600E-wildtype histiocytoses. The purpose of this review is to outline recent molecular advances in histiocytic neoplasms and discuss their impact on the pathogenesis and treatment of these disorders. RECENT FINDINGS: Activating kinase alterations discovered in BRAF V600E-wildtype Langerhans (LCH) and non-Langerhans cell histiocytoses (non-LCH) result in constitutive activation of the mitogen-activated protein kinase and/or phosphoinositide 3-kinases-Akt murine thymoma pathways...
July 2016: Current Opinion in Hematology
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