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Omar Abdel-Wahab

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https://www.readbyqxmd.com/read/28545085/splicing-factor-sf3b1k700e-mutant-dysregulates-erythroid-differentiation-via-aberrant-alternative-splicing-of-transcription-factor-tal1
#1
Shuiling Jin, Hairui Su, Ngoc-Tung Tran, Jing Song, Sydney S Lu, Ying Li, Suming Huang, Omar Abdel-Wahab, Yanyan Liu, Xinyang Zhao
More than 60% of myeloid dysplasia syndrome (MDS) contains mutations in genes encoding for splicing factors such as SF3B1, U2AF, SRSF2 and ZRSR2. Mutations in SF3B1 are associated with 80% cases of refractory anemia with ring sideroblast (RARS), a subtype of MDS. SF3B1K700E is the most frequently mutated site among mutations on SF3B1. Yet the molecular mechanisms on how mutations of splicing factors lead to defective erythropoiesis are not clear. SF3B1K700E mutant binds to an RNA binding protein, RBM15, stronger than the wild type SF3B1 protein in co-immunoprecipitation assays...
2017: PloS One
https://www.readbyqxmd.com/read/28516957/asxl2-is-essential-for-haematopoiesis-and-acts-as-a-haploinsufficient-tumour-suppressor-in-leukemia
#2
Jean-Baptiste Micol, Alessandro Pastore, Daichi Inoue, Nicolas Duployez, Eunhee Kim, Stanley Chun-Wei Lee, Benjamin H Durham, Young Rock Chung, Hana Cho, Xiao Jing Zhang, Akihide Yoshimi, Andrei Krivtsov, Richard Koche, Eric Solary, Amit Sinha, Claude Preudhomme, Omar Abdel-Wahab
Additional sex combs-like (ASXL) proteins are mammalian homologues of additional sex combs (Asx), a regulator of trithorax and polycomb function in Drosophila. While there has been great interest in ASXL1 due to its frequent mutation in leukemia, little is known about its paralog ASXL2, which is frequently mutated in acute myeloid leukemia patients bearing the RUNX1-RUNX1T1 (AML1-ETO) fusion. Here we report that ASXL2 is required for normal haematopoiesis with distinct, non-overlapping effects from ASXL1 and acts as a haploinsufficient tumour suppressor...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28512190/hematopoietic-origin-of-langerhans-cell-histiocytosis-and-erdheim-chester-disease-in-adults
#3
Paul Milne, Venetia Bigley, Chris M Bacon, Antoine Néel, Naomi McGovern, Simon Bomken, Muzlifah Haniffa, Eli L Diamond, Benjamin H Durham, Johannes Visser, David Hunt, Harsha Gunawardena, Mac Macheta, Kenneth L McClain, Carl Allen, Omar Abdel-Wahab, Matthew Collin
Langerhans cell histiocytosis (LCH) and Erdheim Chester Disease (ECD) are rare histiocytic disorders induced by somatic mutation of MAP kinase pathway genes. BRAF(V600E) mutation is the most common mutation in both conditions and also occurs in the hematopoietic neoplasm hairy cell leukemia (HCL). It is not known if adult LCH or ECD arise from hematopoietic stem cells (HSC) nor which potential blood borne precursors lead to the formation of histiocytic lesions. In this study, BRAF V600E allele-specific PCR was used to map the neoplastic clone in 20 adults with LCH ECD and HCL...
May 16, 2017: Blood
https://www.readbyqxmd.com/read/28468827/hmg-coa-synthase-1-is-a-synthetic-lethal-partner-of-braf-v600e-in-human-cancers
#4
Liang Zhao, Jun Fan, Siyuan Xia, Yaozhu Pan, Shuangping Liu, Guoqing Qian, Zhiyu Qian, Hee-Bum Kang, Jack L Arbiser, Brian P Pollack, Ragini Kudchadkar, David H Lawson, Michael Rossi, Omar Abdel-Wahab, Taha Merghoub, Hanna J Khoury, Fadlo R Khuri, Lawrence H Boise, Sagar Lonial, Fangping Chen, Jing Chen, Ruiting Lin
Contributions of metabolic changes to cancer development and maintenance have received increasing attention in recent years. Although many human cancers share similar metabolic alterations, it remains unclear whether oncogene-specific metabolic alterations are required for tumor development. Using RNAi-based screen targeting the majority of the known metabolic proteins, we recently found that oncogenic BRAF(V600E) upregulates HMG-CoA lyase (HMGCL), which converts HMG-CoA to acetyl-CoA and a ketone body, acetoacetate, that selectively enhances BRAFV600E-dependent MEK1 activation in human cancer...
May 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28466384/splicing-factor-mutations-in-mds-rars-and-mds-mpn-rs-t
#5
REVIEW
Akihide Yoshimi, Omar Abdel-Wahab
Spliceosomal mutations, especially mutations in SF3B1, are frequently (>80%) identified in patients with refractory anemia with ringed sideroblasts (RARS) and myelodysplastic/myeloproliferative neoplasms with ringed sideroblasts and thrombocytosis (MDS/MPN-RS-T; previously known as RARS-T), and SF3B1 mutations have a high positive predictive value for disease phenotype with ringed sideroblasts. These observations suggest that SF3B1 mutations play important roles in the pathogenesis of these disorders and formation of ringed sideroblasts...
June 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28408421/modeling-cbl-activating-mutations-in-vivo
#6
Stanley Chun-Wei Lee, Omar Abdel-Wahab
No abstract text is available yet for this article.
April 13, 2017: Blood
https://www.readbyqxmd.com/read/28348147/how-do-messenger-rna-splicing-alterations-drive-myelodysplasia
#7
REVIEW
Poorval Joshi, Stephanie Halene, Omar Abdel-Wahab
Mutations in RNA splicing factors are the single most common class of genetic alterations in myelodysplastic syndrome (MDS) patients. Although much has been learned about how these mutations affect splicing at a global- and transcript-specific level, critical questions about the role of these mutations in MDS development and maintenance remain. Here we present the questions to be addressed in order to understand the unique enrichment of these mutations in MDS.
May 4, 2017: Blood
https://www.readbyqxmd.com/read/28330793/procedural-and-clinical-outcomes-in-transcatheter-aortic-valve-replacement-for-bicuspid-versus-tricuspid-aortic-valve-stenosis
#8
Sung-Han Yoon, Sabine Bleiziffer, Ole De Backer, Victoria Delgado, Takahide Arai, Johannes Ziegelmueller, Marco Barbanti, Rahul Sharma, Gidon Y Perlman, Omar K Khalique, Erik W Holy, Smriti Saraf, Florian Deuschl, Buntaro Fujita, Philipp Ruile, Franz-Josef Neumann, Gregor Pache, Masao Takahashi, Hidehiro Kaneko, Tobias Schmidt, Yohei Ohno, Niklas Schofer, William K F Kong, Edgar Tay, Daisuke Sugiyama, Hiroyuki Kawamori, Yoshio Maeno, Yigal Abramowitz, Tarun Chakravarty, Mamoo Nakamura, Shingo Kuwata, Gerald Yong, Hsien-Li Kao, Michael Lee, Hyo-Soo Kim, Thomas Modine, S Chiu Wong, Francesco Bedgoni, Luca Testa, Emmanuel Teiger, Christian Butter, Stephan M Ensminger, Ulrich Schaefer, Danny Dvir, Philipp Blanke, Jonathon Leipsic, Fabian Nietlispach, Mohamed Abdel-Wahab, Bernard Chevalier, Corrado Tamburino, David Hildick-Smith, Brian K Whisenant, Seung-Jung Park, Antonio Colombo, Azeem Latib, Susheel K Kodali, Jeroen J Bax, Lars Søndergaard, John G Webb, Thierry Lefèvre, Martin B Leon, Raj Makkar
BACKGROUND: Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve stenosis (AS) is being increasingly performed. OBJECTIVES: From the Bicuspid AS TAVR multicenter registry, the procedural and clinical outcomes in patients with bicuspid versus tricuspid AS were compared. METHODS: Outcomes of 561 patients with bicuspid AS and 4,546 patients with tricuspid AS were compared after propensity-score matching assembling 546 pairs of patients with similar baseline characteristics...
March 15, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28304277/partial-loss-of-genes-might-open-therapeutic-window
#9
Bo Liu, Omar Abdel-Wahab
The loss of genes that encode RNA splicing factors weakens cancer cells in a way that could be exploited by new approaches to treatment.
March 17, 2017: ELife
https://www.readbyqxmd.com/read/28214412/histiocytoses-emerging-neoplasia-behind-inflammation
#10
REVIEW
Julien Haroche, Fleur Cohen-Aubart, Barret J Rollins, Jean Donadieu, Frédéric Charlotte, Ahmed Idbaih, Augusto Vaglio, Omar Abdel-Wahab, Jean-François Emile, Zahir Amoura
Histiocytoses are disorders characterised by inflammation and the accumulation of cells derived from the monocyte and macrophage lineages, which results in tissue damage. Although they are often considered rare disorders with protean clinical manifestations, considerable advances in the understanding of their genetics have led to increased clinical recognition of these conditions, and fuelled further insights into their pathogenesis. In this Review, we describe insights into the cells of origin, molecular pathology, clinical features, and treatment strategies for some of the most common histiocytic disorders, including Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease...
February 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28089569/prevention-of-dietary-fat-fueled-ketogenesis-attenuates-braf-v600e-tumor-growth
#11
Siyuan Xia, Ruiting Lin, Lingtao Jin, Liang Zhao, Hee-Bum Kang, Yaozhu Pan, Shuangping Liu, Guoqing Qian, Zhiyu Qian, Evmorfia Konstantakou, Baotong Zhang, Jin-Tang Dong, Young Rock Chung, Omar Abdel-Wahab, Taha Merghoub, Lu Zhou, Ragini R Kudchadkar, David H Lawson, Hanna J Khoury, Fadlo R Khuri, Lawrence H Boise, Sagar Lonial, Benjamin H Lee, Brian P Pollack, Jack L Arbiser, Jun Fan, Qun-Ying Lei, Jing Chen
Lifestyle factors, including diet, play an important role in the survival of cancer patients. However, the molecular mechanisms underlying pathogenic links between diet and particular oncogenic mutations in human cancers remain unclear. We recently reported that the ketone body acetoacetate selectively enhances BRAF V600E mutant-dependent MEK1 activation in human cancers. Here we show that a high-fat ketogenic diet increased serum levels of acetoacetate, leading to enhanced tumor growth potential of BRAF V600E-expressing human melanoma cells in xenograft mice...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/27903528/consensus-guidelines-for-the-diagnosis-and-management-of-patients-with-classic-hairy-cell-leukemia
#12
REVIEW
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. Because 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...
February 2, 2017: 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
#13
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...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27836865/molecular-pathways-understanding-and-targeting-mutant-spliceosomal-proteins
#14
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 that performs splicing, which is 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 include change-of-function mutations in genes encoding spliceosomal proteins. Such mutations are among the most common genetic alterations in myeloid and lymphoid leukemias, making efforts to therapeutically target cells bearing these mutations critical...
January 15, 2017: 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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