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JOURNAL ARTICLE
Vishnupriyadevi Parvathareddy, Umut Selamet, Aditi A Sen, Omar Mamlouk, Juhee Song, Valda D Page, Maen Abdelrahim, Adi Diab, Noha Abdel-Wahab, Ala Abudayyeh
Background: Immune-related adverse events (irAEs) challenge the use of immune checkpoint inhibitors (ICIs). We performed a retrospective study to evaluate response to infliximab for immune-related adverse event management, and infliximab's effect on progression-free survival (PFS) and overall survival (OS) with a focus on melanoma and genitourinary cancers. Methods: We retrospectively reviewed records of all cancer patients exposed to infliximab after immune checkpoint inhibitor (ICI) treatment from 2004 to 2021 at the MD Anderson Cancer Center...
October 27, 2023: Cancers
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JOURNAL ARTICLE
Guo Ge, Peng Zhang, Pinpin Sui, Shi Chen, Hui Yang, Ying Guo, Ivan P Rubalcava, Asra Noor, Caroline R Delma, Joel Agosto-Peña, Hui Geng, Edward A Medina, Ying Liang, Stephen D Nimer, Ruben Mesa, Omar Abdel-Wahab, Mingjiang Xu, Feng-Chun Yang
ASXL1 mutation frequently occurs in all forms of myeloid malignancies and is associated with aggressive disease and poor prognosis. ASXL1 recruits Polycomb repressive complex 2 (PRC2) to specific gene loci to repress transcription through trimethylation of histone H3 on lysine 27 (H3K27me3). ASXL1 alterations reduce H3K27me3 levels, which results in leukemogenic gene expression and the development of myeloid malignancies. Standard therapies for myeloid malignancies have limited efficacy when mutated ASXL1 is present...
January 2, 2024: Journal of Clinical Investigation
#23
JOURNAL ARTICLE
Claudia Bruedigam, Amy H Porter, Axia Song, Gerjanne Vroeg In de Wei, Thomas Stoll, Jasmin Straube, Leanne Cooper, Guidan Cheng, Vivian F S Kahl, Alexander P Sobinoff, Victoria Y Ling, Billy Michael Chelliah Jebaraj, Yashaswini Janardhanan, Rohit Haldar, Laura J Bray, Lars Bullinger, Florian H Heidel, Glen A Kennedy, Michelle M Hill, Hilda A Pickett, Omar Abdel-Wahab, Gunter Hartel, Steven W Lane
Telomerase enables replicative immortality in most cancers including acute myeloid leukemia (AML). Imetelstat is a first-in-class telomerase inhibitor with clinical efficacy in myelofibrosis and myelodysplastic syndromes. Here, we develop an AML patient-derived xenograft resource and perform integrated genomics, transcriptomics and lipidomics analyses combined with functional genetics to identify key mediators of imetelstat efficacy. In a randomized phase II-like preclinical trial in patient-derived xenografts, imetelstat effectively diminishes AML burden and preferentially targets subgroups containing mutant NRAS and oxidative stress-associated gene expression signatures...
October 30, 2023: Nature Cancer
#24
JOURNAL ARTICLE
Ryan N Ptashkin, Mark D Ewalt, Gowtham Jayakumaran, Iwona Kiecka, Anita S Bowman, JinJuan Yao, Jacklyn Casanova, Yun-Te David Lin, Kseniya Petrova-Drus, Abhinita S Mohanty, Ruben Bacares, Jamal Benhamida, Satshil Rana, Anna Razumova, Chad Vanderbilt, Anoop Balakrishnan Rema, Ivelise Rijo, Julie Son-Garcia, Ino de Bruijn, Menglei Zhu, Sean Lachhander, Wei Wang, Mohammad S Haque, Venkatraman E Seshan, Jiajing Wang, Ying Liu, Khedoudja Nafa, Laetitia Borsu, Yanming Zhang, Umut Aypar, Sarah P Suehnholz, Debyani Chakravarty, Jae H Park, Omar Abdel-Wahab, Anthony R Mato, Wenbin Xiao, Mikhail Roshal, Mariko Yabe, Connie Lee Batlevi, Sergio Giralt, Gilles Salles, Raajit Rampal, Martin Tallman, Eytan M Stein, Anas Younes, Ross L Levine, Miguel-Angel Perales, Marcel R M van den Brink, Ahmet Dogan, Marc Ladanyi, Michael F Berger, A Rose Brannon, Ryma Benayed, Ahmet Zehir, Maria E Arcila
Genomic profiling of hematologic malignancies has augmented our understanding of variants that contribute to disease pathogenesis and supported development of prognostic models that inform disease management in the clinic. Tumor only sequencing assays are limited in their ability to identify definitive somatic variants, which can lead to ambiguity in clinical reporting and patient management. Here, we describe the MSK-IMPACT Heme cohort, a comprehensive data set of somatic alterations from paired tumor and normal DNA using a hybridization capture-based next generation sequencing platform...
October 28, 2023: Nature Communications
#25
JOURNAL ARTICLE
Jean-François Emile, Zofia Hélias-Rodzewicz, Benjamin Heath Durham, Sébastien Héritier, Malik da Silva, Komel Younas, Fleur Cohen-Aubart, Omar I Abdel-Wahab, Eli L Diamond, Jean Donadieu, Julien Haroche
No abstract text is available yet for this article.
October 25, 2023: Blood Advances
#26
JOURNAL ARTICLE
Benjamin H Durham, Oshrat Hershkovitz-Rokah, Omar I Abdel-Wahab, Mariko Yabe, Young Rock Chung, Gilad Itchaki, Maayan Ben-Sasson, Vered A Asher-Guz, David Groshar, Seyram A Doe-Tetteh, Tina Alano, David B Solit, Ofer Shpilberg, Eli L Diamond, Roei D Mazor
Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterized by the accumulation of clonal mononuclear phagocyte system cells expressing CD1a and CD207. In the past decade, molecular profiling of LCH, as well as other histiocytic neoplasms demonstrated that these diseases are driven by MAP kinase (MAPK) activating alterations, with somatic BRAFV600E mutations in >50% of LCH patients, and clinical inhibition of MAPK signaling has demonstrated remarkable clinical efficacy. At the same time, activating alterations in kinase-encoding genes such as PIK3CA, ALK, RET, and CSF1R which can activate mitogenic pathways independent from the MAPK pathway have been reported in a subset of histiocytic neoplasms with anecdotal evidence of successful targeted treatment of histiocytoses harboring driver alterations in RET, ALK, and CSF1R...
October 23, 2023: Blood Advances
#27
JOURNAL ARTICLE
Katherine Knorr, Jahan Rahman, Caroline Erickson, Eric Wang, Mara Monetti, Zhuoning Li, Juliana Ortiz-Pacheco, Andrew Jones, Sydney X Lu, Robert F Stanley, Maria Baez, Nina Fox, Cynthia Castro, Alessandra E Marino, Caroline Jiang, Alex Penson, Simon J Hogg, Xiaoli Mi, Hideaki Nakajima, Hiroyoshi Kunimoto, Koutarou Nishimura, Daichi Inoue, Benjamin Greenbaum, David Knorr, Jeffrey Ravetch, Omar Abdel-Wahab
Despite recent advances in the treatment of acute myeloid leukemia (AML), there has been limited success in targeting surface antigens in AML, in part due to shared expression across malignant and normal cells. Here, high-density immunophenotyping of AML coupled with proteogenomics identified unique expression of a variety of antigens, including the RNA helicase U5 snRNP200, on the surface of AML cells but not on normal hematopoietic precursors and skewed Fc receptor distribution in the AML immune microenvironment...
December 2023: Nature Cancer
#28
JOURNAL ARTICLE
Jan Philipp Bewersdorf, Maximilian Stahl, Justin Taylor, Xiaoli Mi, Namrata Sonia Chandhok, Justin Watts, Andriy Derkach, Mateusz Wysocki, Sydney X Lu, Jessie Bourcier, Simon J Hogg, Jahan Rahman, Sana Chaudhry, Tulasigeri M Totiger, Omar Abdel-Wahab, Eytan M Stein
No abstract text is available yet for this article.
October 9, 2023: Leukemia
#29
REVIEW
Ashraf Omar, Ahmed Kaseb, Tamer Elbaz, Mohamed El-Kassas, Amr El Fouly, Abdel Fatah Hanno, Ahmed El Dorry, Ahmed Hosni, Amr Helmy, Amr S Saad, Ashwaq Alolayan, Basem Elsayed Eysa, Emad Hamada, Hamdy Azim, Hany Khattab, Hesham Elghazaly, Hesham Tawfik, Hisham Ayoub, Hussein Khaled, Ibtessam Saadeldin, Imam Waked, Eman M F Barakat, Mahmoud El Meteini, Mohamed Hamed Shaaban, Mohamed EzzElarab, Mohamed Fathy, Mohamed Shaker, Mohamed Sobhi, Mohamed Kamal Shaker, Mohamed ElGharib, Mohammed Abdullah, Mohesn Mokhtar, Mostafa Elshazli, Omar Mohamed Khaleil Heikal, Osama Hetta, Reda Mahmoud ElWakil, Sameh Abdel Wahab, Samir Shehata Eid, Yousri Rostom
Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis...
2023: Journal of Hepatocellular Carcinoma
#30
REVIEW
Maximilian Stahl, Jan Philipp Bewersdorf, Zhuoer Xie, Matteo Giovanni Della Porta, Rami Komrokji, Mina L Xu, Omar Abdel-Wahab, Justin Taylor, David P Steensma, Daniel T Starczynowski, Mikkael A Sekeres, Guillermo Sanz, David A Sallman, Gail J Roboz, Uwe Platzbecker, Mrinal M Patnaik, Eric Padron, Olatoyosi Odenike, Stephen D Nimer, Aziz Nazha, Ravi Majeti, Sanam Loghavi, Richard F Little, Alan F List, Tae Kon Kim, Christopher S Hourigan, Robert P Hasserjian, Stephanie Halene, Elizabeth A Griffiths, Steven D Gore, Peter Greenberg, Maria E Figueroa, Pierre Fenaux, Fabio Efficace, Amy E DeZern, Naval G Daver, Jane E Churpek, Hetty E Carraway, Rena Buckstein, Andrew M Brunner, Jacqueline Boultwood, Uma Borate, Rafael Bejar, John M Bennett, Andrew H Wei, Valeria Santini, Michael R Savona, Amer M Zeidan
The guidelines for classification, prognostication, and response assessment of myelodysplastic syndromes/neoplasms (MDS) have all recently been updated. In this report on behalf of the International Consortium for MDS (icMDS) we summarize these developments. We first critically examine the updated World Health Organization (WHO) classification and the International Consensus Classification (ICC) of MDS. We then compare traditional and molecularly based risk MDS risk assessment tools. Lastly, we discuss limitations of criteria in measuring therapeutic benefit and highlight how the International Working Group (IWG) 2018 and 2023 response criteria addressed these deficiencies and are endorsed by the icMDS...
November 2023: Blood Reviews
#31
JOURNAL ARTICLE
Mariela Cortés-López, Paulina Chamely, Allegra G Hawkins, Robert F Stanley, Ariel D Swett, Saravanan Ganesan, Tarek H Mouhieddine, Xiaoguang Dai, Lloyd Kluegel, Celine Chen, Kiran Batta, Nili Furer, Rahul S Vedula, John Beaulaurier, Alexander W Drong, Scott Hickey, Neville Dusaj, Gavriel Mullokandov, Adam M Stasiw, Jiayu Su, Ronan Chaligné, Sissel Juul, Eoghan Harrington, David A Knowles, Catherine J Potenski, Daniel H Wiseman, Amos Tanay, Liran Shlush, Robert C Lindsley, Irene M Ghobrial, Justin Taylor, Omar Abdel-Wahab, Federico Gaiti, Dan A Landau
RNA splicing factors are recurrently mutated in clonal blood disorders, but the impact of dysregulated splicing in hematopoiesis remains unclear. To overcome technical limitations, we integrated genotyping of transcriptomes (GoT) with long-read single-cell transcriptomics and proteogenomics for single-cell profiling of transcriptomes, surface proteins, somatic mutations, and RNA splicing (GoT-Splice). We applied GoT-Splice to hematopoietic progenitors from myelodysplastic syndrome (MDS) patients with mutations in the core splicing factor SF3B1...
August 9, 2023: Cell Stem Cell
#32
JOURNAL ARTICLE
Javier Martínez-López, Ana Márquez, Francesco Pegoraro, Lourdes Ortiz-Fernández, Marialbert Acosta-Herrera, Martin Kerick, Elena Gelain, Eli L Diamond, Benjamin H Durham, Omar Abdel-Wahab, Ronald S Go, Matthew J Koster, Lorenzo Dagna, Corrado Campochiaro, Matthew Collin, Paul Milne, Juvianee I Estrada-Veras, Kevin O'Brien, Matthias Papo, Fleur Cohen-Aubar, Zahir Amoura, Julien Haroche, Javier Martín, Augusto Vaglio
OBJECTIVE: Erdheim-Chester disease (ECD) is rare histiocytosis with a wide range of clinical manifestations. Somatic mutations are key to the pathogenesis of the disease; however, the relationship between germline genetic variants and ECD has not been examined so far. The present study aims to explore the inherited genetic component of ECD by performing the first genome-wide association study. METHODS: After quality controls, a cohort of 255 ECD patients and 7,471 healthy donors was included in this study...
August 10, 2023: Arthritis & Rheumatology
#33
JOURNAL ARTICLE
Youmna S Kfoury, Fei Ji, Esha Jain, Michael C Mazzola, Giulia Schiroli, Ani Papazian, Francois Emile Mercier, David Brian Sykes, Anna Kiem, Mark A Randolph, Omar I Abdel-Wahab, Laura Maria Calvi, Ruslan Sadreyev, David T Scadden
Myelodysplastic syndromes (MDS) are a heterogenous group of diseases affecting the hematopoietic stem cell that are curable only by stem cell transplantation. Both hematopoietic cell intrinsic changes and extrinsic signals from the bone marrow (BM) niche seem to ultimately lead to MDS. Animal models of MDS indicate that alterations in specific mesenchymal progenitor subsets in the BM microenvironment can induce or select for abnormal hematopoietic cells. Here we identify a subset of human BM mesenchymal cells marked by the expression of CD271, CD146 and CD106...
July 14, 2023: Blood Advances
#34
JOURNAL ARTICLE
Anne S Reiner, Benjamin H Durham, Mariko Yabe, Kseniya Petrova-Drus, Jasmine H Francis, Raajit K Rampal, Mario E Lacouture, Veronica Rotemberg, Omar Abdel-Wahab, Katherine S Panageas, Eli L Diamond
Little is known about outcomes following interruption of targeted therapy in adult patients with histiocytic neoplasms. This is an IRB-approved study of patients with histiocytic neoplasms whose BRAF and MEK inhibitors were interrupted after achieving complete or partial response by 18-fluorodeoxyglucose positron emission tomography (FDG-PET). 17/22 (77%) of patients experienced disease relapse following treatment interruption. Achieving a complete response prior to interruption, having a mutation other than BRAFV600E, and receiving MEK inhibition only were each associated with a statistically significant improvement in relapse-free survival...
July 3, 2023: British Journal of Haematology
#35
JOURNAL ARTICLE
Eli L Diamond, Jasmine H Francis, Mario E Lacouture, Veronica Rotemberg, Mariko Yabe, Kseniya Petrova-Drus, Gary A Ulaner, Ryan Reddy, Omar Abdel-Wahab, Benjamin H Durham
No abstract text is available yet for this article.
June 24, 2023: Leukemia
#36
JOURNAL ARTICLE
Pu Zhang, Omar Abdel-Wahab
In this issue of Molecular Cell, Yu et al.1 identify RBM33 as a previously unrecognized m6 A (N-6-methyladenosine) RNA binding protein that plays a critical role in ALKBH5-mediated m6 A demethylation of a subset of mRNA transcripts by forming a complex with ALKBH5.
June 15, 2023: Molecular Cell
#37
JOURNAL ARTICLE
Sanam Shahid, Nicholas Ceglia, Jean-Benoit Le Luduec, Andrew McPherson, Barbara Spitzer, Theodota Kontopoulos, Viktoria Bojilova, M Kazim Panjwani, Mikhail Roshal, Sohrab Shah, Omar I Abdel-Wahab, Benjamin D Greenbaum, Katharine C Hsu
Although allogeneic hematopoietic cell transplantation (allo-HCT) is curative for high-risk pediatric acute myeloid leukemia (AML), disease relapse remains the primary cause of post-transplant mortality. To identify pressures imposed by allo-HCT on AML cells that escape the graft-versus-leukemia effect, we evaluated immune signatures at diagnosis and post-transplant relapse in bone marrow samples from four pediatric patients using a multimodal single-cell proteogenomic approach. Downregulation of MHC class II expression was most profound in progenitor-like blasts and accompanied by correlative changes in transcriptional regulation...
June 16, 2023: Blood Advances
#38
JOURNAL ARTICLE
Sara Zarnegar-Lumley, Todd Alonzo, Robert B Gerbing, Megan Othus, Zhuoxin Sun, Rhonda E Ries, Jim Wang, Amanda R Leonti, Matthew A Kutny, Fabiana Ostronoff, Jerald P Radich, Frederick R Appelbaum, Era L Pogosova-Agadjanyan, Kristen M O'Dwyer, Martin S Tallman, Mark R Litzow, Ehab Atallah, Todd M Cooper, Richard Aplenc, Omar I Abdel-Wahab, Alan S Gamis, Selina M Luger, Harry P Erba, Ross L Levine, E Anders Kolb, Derek L Stirewalt, Soheil Meshinchi, Katherine Tarlock
Somatic mutations in isocitrate dehydrogenase (IDH) genes occur frequently in adult acute myeloid leukemia (AML) and less commonly in pediatric AML. The objective of this study was to describe the prevalence, co-occurring mutational profile, and prognostic significance of IDH mutations in AML across the age spectrum. Our cohort included 3,141 patients aged <1 month-88 years treated on CCG/COG (N=1872), SWOG (N=359), ECOG (N=397) trials and in Beat AML (N=333) and TCGA (N=180) genomic characterization cohorts...
June 2, 2023: Blood Advances
#39
JOURNAL ARTICLE
Seemon Coomar, Pedro Mota, Alexander Penson, Jürg Schwaller, Omar Abdel-Wahab, Dennis Gillingham
UNLABELLED: Certain arylsulfonamides (ArSulf) induce an interaction between the E3 ligase substrate adaptor DCAF15 and the critical splicing factor RBM39, ultimately causing its degradation. However, degradation of a splicing factor introduces complex pleiotropic effects that are difficult to untangle, since, aside from direct protein degradation, downstream transcriptional effects also influence the proteome. By overlaying transcriptional data and proteome datasets, we distinguish transcriptional from direct degradation effects, pinpointing those proteins most impacted by splicing changes...
May 31, 2023: Molecular Cancer Research: MCR
#40
JOURNAL ARTICLE
Seemon Coomar, Pedro Mota, Alexander Penson, Juerg Schwaller, Omar Abdel-Wahab, Dennis Gillingham
Certain arylsulfonamides (ArSulfs) induce an interaction between the E3 ligase substrate adaptor DCAF15 and the critical splicing factor RBM39, ultimately causing its degradation. However, degradation of a splicing factor introduces complex pleiotropic effects that are difficult to untangle, since, aside from direct protein degradation, downstream transcriptional effects also influence the proteome. By overlaying transcriptional data and proteome datasets, we distinguish transcriptional from direct degradation effects, pinpointing those proteins most impacted by splicing changes...
May 12, 2023: Molecular Cancer Research: MCR
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