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Omar Abdel-Wahab

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https://www.readbyqxmd.com/read/27903528/consensus-guidelines-for-the-diagnosis-and-management-of-patients-with-classic-hairy-cell-leukemia
#1
Michael R Grever, Omar Abdel-Wahab, Leslie A Andritsos, Versha Banerji, Jacqueline Barrientos, James S Blachly, Timothy G Call, Daniel Catovsky, Claire Dearden, Judit Demeter, Monica Else, Francesco Forconi, Alessandro Gozzetti, Anthony D Ho, James B Johnston, Jeffrey Jones, Gunnar Juliusson, Eric Kraut, Robert J Kreitman, Loree Larratt, Francesco Lauria, Gerard Lozanski, Emili Montserrat, Sameer A Parikh, Jae H Park, Aaron Polliack, Graeme R Quest, Kanti R Rai, Farhad Ravandi, Tadeusz Robak, Alan Saven, John F Seymour, Tamar Tadmor, Martin S Tallman, Constantine Tam, Enrico Tiacci, Xavier Troussard, Clive S Zent, Thorsten Zenz, Pier Luigi Zinzani, Brunangelo Falini
Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. As more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease...
November 30, 2016: Blood
https://www.readbyqxmd.com/read/27863426/quantification-of-tumor-derived-cell-free-dna-cfdna-by-digital-pcr-digpcr-in-cerebrospinal-fluid-of-patients-with-brafv600-mutated-malignancies
#2
Parisa Momtaz, Elena Pentsova, Omar Abdel-Wahab, Eli Diamond, David Hyman, Taha Merghoub, Daoqi You, Billel Gasmi, Agnes Viale, Paul B Chapman
Tumor-derived cell free DNA (cfDNA) can be detected in plasma. We hypothesized that mutated BRAF V600 cfDNA could be quantified in the cerebrospinal fluid (CSF) of patients with central nervous system (CNS) metastases. We collected CSF from patients with BRAF V600E or K-mutated melanoma (N=8) or BRAF V600E mutated Erdheim-Chester Disease (ECD) (N=3) with suspected central nervous system (CNS) involvement on the basis of neurological symptoms (10/11), MRI imaging (8/11), or both. Tumor-derived cfDNA was quantified by digital PCR in the CSF of 6/11 patients (range from 0...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27836865/molecular-pathways-understanding-and-targeting-mutant-spliceosomal-proteins
#3
Akihide Yoshimi, Omar Abdel-Wahab
Splicing of precursor messenger RNA is a critical step in regulating gene expression and major advances are being made in understanding the composition and structure of the enzymatic complex which performs splicing, termed the spliceosome. In parallel, there has been increased appreciation for diverse mechanisms by which alterations in splicing contribute to cancer pathogenesis. Key among these includes change-of-function mutations in genes encoding spliceosomal proteins. Such mutations are amongst the most common genetic alterations in myeloid and lymphoid leukemias, making efforts to therapeutically target cells bearing these mutations critical...
November 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27798785/spray-diathermy-versus-harmonic-scalpel-technique-for-hepatic-parenchymal-transection-of-living-donor
#4
Mohamed El Shobary, Tarek Salah, Ayman El Nakeeb, Ahmad M Sultan, Ahmed Elghawalby, Omar Fathy, Mohamed Abdel Wahab, Amro Yassen, Mohamed Elmorshedy, Wagdi F Elkashef, Usama Shiha, Mohamed Elsadany
BACKGROUND: Liver parenchymal transection is the most invasive and challenging part in the living donor operation. The study was planned to compare the safety, efficacy, and outcome of harmonic scalpel versus spray diathermy as a method of parenchymal liver transection in donor hepatectomy. PATIENT AND METHOD: Eighty consecutive patients, who were treated by living donor liver transplantation (LDLT), were included in the study. The study population was divided into two groups according to the method of liver transection: group A by harmonic scalpel (HS) and group B by spray diathermy (SD)...
October 31, 2016: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/27663730/genetic-drivers-of-vulnerability-and-resistance-in-relapsed-acute-lymphoblastic-leukemia
#5
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
https://www.readbyqxmd.com/read/27622329/modeling-sf3b1-mutations-in-cancer-advances-challenges-and-opportunities
#6
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
https://www.readbyqxmd.com/read/27603132/therapeutic-targeting-of-splicing-in-cancer
#7
REVIEW
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
https://www.readbyqxmd.com/read/27539994/defining-risk-in-mds-over-time
#8
Akihide Yoshimi, Omar Abdel-Wahab
No abstract text is available yet for this article.
August 18, 2016: Blood
https://www.readbyqxmd.com/read/27535996/anakinra-as-efficacious-therapy-for-two-cases-of-intracranial-erdheim-chester-disease
#9
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
https://www.readbyqxmd.com/read/27527698/the-role-of-additional-sex-combs-like-proteins-in-cancer
#10
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
https://www.readbyqxmd.com/read/27516392/impact-of-donor-recipient-genetic-relationship-on-outcome-of-living-donor-liver-transplantation
#11
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
https://www.readbyqxmd.com/read/27505670/ezh2-and-bcl6-cooperate-to-assemble-cbx8-bcor-complex-to-repress-bivalent-promoters-mediate-germinal-center-formation-and-lymphomagenesis
#12
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
https://www.readbyqxmd.com/read/27478938/emerging-concepts-of-epigenetic-dysregulation-in-hematological-malignancies
#13
REVIEW
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
https://www.readbyqxmd.com/read/27352931/asxl1-plays-an-important-role-in-erythropoiesis
#14
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
https://www.readbyqxmd.com/read/27351754/treatment-outcomes-and-secondary-cancer-incidence-in-young-patients-with-hairy-cell-leukaemia
#15
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...
November 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27344947/epigenetic-perturbations-by-arg882-mutated-dnmt3a-potentiate-aberrant-stem-cell-gene-expression-program-and-acute-leukemia-development
#16
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
https://www.readbyqxmd.com/read/27282250/rna-splicing-factors-as-oncoproteins-and-tumour-suppressors
#17
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
https://www.readbyqxmd.com/read/27270779/erratum-modulation-of-splicing-catalysis-for-therapeutic-targeting-of-leukemia-with-mutations-in-genes-encoding-spliceosomal-proteins
#18
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
https://www.readbyqxmd.com/read/27270773/reply-to-uveal-melanoma-cells-are-resistant-to-ezh2-inhibition-regardless-of-bap1-status
#19
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
https://www.readbyqxmd.com/read/27240645/contemporary-insights-into-the-pathogenesis-and-treatment-of-chronic-myeloproliferative-neoplasms
#20
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
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