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JOURNAL ARTICLE
Shimaa A Amer, Ahmed Gouda, Gehan K Saleh, Arwa H Nassar, Abdel-Wahab A Abdel-Warith, Elsayed M Younis, Dalia E Altohamy, Maha S Kilany, Simon J Davies, Anaam E Omar
This investigation explored the impact of dietary frankincense resin oil (FO) on growth performance parameters, intestinal histomorphology, fatty acid composition of the breast muscle, and the immune status of broilers. We allotted 400, three-day-old, male chicks (Ross 308 broiler) into four treatment groups (ten replicates/group; ten chicks/replicate). They were fed a basal diet with different concentrations of FO (0, 200, 400, and 600 mg kg-1 ). FO supplementation increased the overall body weight (BW) and body weight gain (BWG) by different amounts, linearly improving the feed conversion ratio with the in-supplementation level...
March 7, 2023: Animals: An Open Access Journal From MDPI
#42
REVIEW
Jan Philipp Bewersdorf, Zhuoer Xie, Rafael Bejar, Uma Borate, Jacqueline Boultwood, Andrew M Brunner, Rena Buckstein, Hetty E Carraway, Jane E Churpek, Naval G Daver, Matteo Giovanni Della Porta, Amy E DeZern, Pierre Fenaux, Maria E Figueroa, Steven D Gore, Elizabeth A Griffiths, Stephanie Halene, Robert P Hasserjian, Christopher S Hourigan, Tae Kon Kim, Rami Komrokji, Vijay K Kuchroo, Alan F List, Sanam Loghavi, Ravindra Majeti, Olatoyosi Odenike, Mrinal M Patnaik, Uwe Platzbecker, Gail J Roboz, David A Sallman, Valeria Santini, Guillermo Sanz, Mikkael A Sekeres, Maximilian Stahl, Daniel T Starczynowski, David P Steensma, Justin Taylor, Omar Abdel-Wahab, Mina L Xu, Michael R Savona, Andrew H Wei, Amer M Zeidan
Biological events that contribute to the pathogenesis of myelodysplastic syndromes/neoplasms (MDS) are becoming increasingly characterized and are being translated into rationally designed therapeutic strategies. Herein, we provide updates from the first International Workshop on MDS (iwMDS) of the International Consortium for MDS (icMDS) detailing recent advances in understanding the genetic landscape of MDS, including germline predisposition, epigenetic and immune dysregulation, the complexities of clonal hematopoiesis progression to MDS, as well as novel animal models of the disease...
July 2023: Blood Reviews
#43
COMMENT
Seyram A Doe-Tetteh, Sabrina Y Camp, Dalicia Reales, Jett Crowdis, Anne Marie Noronha, Bernadette Wolff, Tina Alano, Jesse Galle, S Duygu Selcuklu, Agnes Viale, Nicholas D Socci, Ying L Liu, William P Tew, Carol Aghajanian, Marc Ladanyi, Meng Xiao He, Saud H AlDubayan, Roei David Mazor, Ofer Shpilberg, Oshrat Hershkovitz-Rokah, Jose A Riancho, Jose L Hernandez, M Carmen Gonzalez-Vela, Justin J Buthorn, Manda Wilson, Amy E Webber, Mariko Yabe, Kseniya Petrova-Drus, Marc Rosenblum, Benjamin H Durham, Omar Abdel-Wahab, Michael F Berger, Mark T A Donoghue, Andrew L Kung, Julia Glade Bender, Neerav N Shukla, Samuel A Funt, Ahmet Dogan, Robert A Soslow, Hikmat Al-Ahmadie, Darren R Feldman, Eliezer M Van Allen, Eli L Diamond, David B Solit
PURPOSE: To overcome barriers to genomic testing for patients with rare cancers, we initiated a program to offer free clinical tumor genomic testing worldwide to patients with select rare cancer subtypes. EXPERIMENTAL DESIGN: Patients were recruited through social media outreach and engagement with disease-specific advocacy groups, with a focus on patients with histiocytosis, germ cell tumors (GCT), and pediatric cancers. Tumors were analyzed using the MSK-IMPACT next-generation sequencing assay with the return of results to patients and their local physicians...
July 5, 2023: Clinical Cancer Research
#44
EDITORIAL
Won Jun Kim, Omar Abdel-Wahab
No abstract text is available yet for this article.
February 9, 2023: Blood
#45
JOURNAL ARTICLE
Takeshi Fujino, Omar Abdel-Wahab
Chemical modifications of RNA are regulated by a series of readers, writers, and erasers that dictate gene expression. Two new studies in Cell Stem Cell1 , 2 identify roles for the N6 -methyladenosine (m6 A) methyltransferase METTL16 and the m6 A reader IGF2BP2 in leukemia-initiating cells, illuminating exciting new therapeutic targets for leukemia.
January 5, 2023: Cell Stem Cell
#46
JOURNAL ARTICLE
Eric Wang, Jose Mario Bello Pineda, Won Jun Kim, Sisi Chen, Jessie Bourcier, Maximilian Stahl, Simon J Hogg, Jan Phillipp Bewersdorf, Cuijuan Han, Michael E Singer, Daniel Cui, Caroline E Erickson, Steven M Tittley, Alexander V Penson, Katherine Knorr, Robert F Stanley, Jahan Rahman, Gnana Krishnamoorthy, James A Fagin, Emily Creger, Elizabeth McMillan, Chi-Ching Mak, Matthew Jarvis, Carine Bossard, Darrin M Beaupre, Robert K Bradley, Omar Abdel-Wahab
Therapy resistance is a major challenge in the treatment of cancer. Here, we performed CRISPR-Cas9 screens across a broad range of therapies used in acute myeloid leukemia to identify genomic determinants of drug response. Our screens uncover a selective dependency on RNA splicing factors whose loss preferentially enhances response to the BCL2 inhibitor venetoclax. Loss of the splicing factor RBM10 augments response to venetoclax in leukemia yet is completely dispensable for normal hematopoiesis. Combined RBM10 and BCL2 inhibition leads to mis-splicing and inactivation of the inhibitor of apoptosis XIAP and downregulation of BCL2A1, an anti-apoptotic protein implicated in venetoclax resistance...
January 9, 2023: Cancer Cell
#47
EDITORIAL
Ettaib El Marabti, Omar Abdel-Wahab
Chimeric antigen receptor T (CAR-T) cells directed against CD19 have transformed the therapy of relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). A recent study reports promising activity and safety of CD19 CAR-T cells generated from naïve, stem, and central memory T cells in adults with R/R B-ALL. See related article by Aldoss et al., p. 742.
February 16, 2023: Clinical Cancer Research
#48
JOURNAL ARTICLE
Pathologic Predictors of Response to Treatment of Immune Checkpoint Inhibitor-Induced Kidney Injury.
Ala Abudayyeh, Liye Suo, Heather Lin, Omar Mamlouk, Noha Abdel-Wahab, Amanda Tchakarov
BACKGROUND: Immune-related adverse events are a management challenge in patients receiving immune checkpoint inhibitors (ICIs). The most common renal immune-related adverse event, acute interstitial nephritis (AIN), is associated with patient morbidity and mortality. AIN, characterized by infiltration of renal tissue with immune cells, may be analogous to kidney transplant rejection. We evaluated clinical variables and pathologic findings to identify predictors of renal response and overall survival (OS) in patients with ICI-induced AIN...
October 27, 2022: Cancers
#49
JOURNAL ARTICLE
Salima Benbarche, Omar Abdel-Wahab
No abstract text is available yet for this article.
November 7, 2022: Nature Cell Biology
#50
JOURNAL ARTICLE
Chezi Ganzel, Zhuoxin Sun, Timour Baslan, Yanming Zhang, Mithat Gönen, Omar I Abdel-Wahab, Janis Racevskis, Francine Garrett-Bakelman, Scott W Lowe, Hugo F Fernandez, Rhett Ketterling, Selina M Luger, Mark Litzow, Hillard M Lazarus, Jacob M Rowe, Martin S Tallman, Ross L Levine, Elisabeth Paietta
Measurable residual disease (MRD) assessment provides a potent indicator of the efficacy of anti-leukemic therapy. It is unknown, however, whether integrating MRD with molecular profiling better identifies patients at risk of relapse. To investigate the clinical relevance of MRD in relation to a molecular-based prognostic schema, we measured MRD by flow cytometry in 189 AML patients enrolled in ECOG-ACRIN E1900 trial (NCT00049517) in morphologic complete remission (CR) (28.8 % of the original cohort) representing 44...
December 2022: Leukemia Research
#51
JOURNAL ARTICLE
Maximilian Stahl, Omar Abdel-Wahab, Andrew H Wei, Michael R Savona, Mina L Xu, Zhuoer Xie, Justin Taylor, Daniel T Starczynowski, Guillermo F Sanz, David A Sallman, Valeria Santini, Gail J Roboz, Mrinal M Patnaik, Eric Padron, Olatoyosi Odenike, Aziz Nazha, Stephen D Nimer, Ravindra Majeti, Richard F Little, Steven D Gore, Alan F List, Vijay Kuchroo, Rami S Komrokji, Tae Kon Kim, Nina Kim, Christopher S Hourigan, Robert P Hasserjian, Stephanie Halene, Elizabeth A Griffiths, Peter L Greenberg, Maria E Figueroa, Pierre Fenaux, Fabio Efficace, Amy E DeZern, Matteo G Della Porta, Naval G Daver, Jane E Churpek, Hetty E Carraway, Andrew M Brunner, Uma Borate, John M Bennett, Rafael Bejar, Jacqueline Boultwood, Sanam Loghavi, Jan Philipp Bewersdorf, Uwe Platzbecker, David P Steensma, Mikkael A Sekeres, Rena J Buckstein, Amer M Zeidan
No abstract text is available yet for this article.
October 19, 2022: Blood Advances
#52
JOURNAL ARTICLE
Maximilian Stahl, Andriy Derkach, Noushin Farnoud, Jan Philipp Bewersdorf, Troy Robinson, Christopher Famulare, Christina Cho, Sean Devlin, Kamal Menghrajani, Minal A Patel, Sheng F Cai, Linde A Miles, Robert L Bowman, Mark B Geyer, Andrew Dunbar, Zachary D Epstein-Peterson, Erin McGovern, Jessica Schulman, Jacob L Glass, Justin Taylor, Aaron D Viny, Eytan M Stein, Bartlomiej Getta, Maria E Arcila, Qi Gao, Juliet Barker, Brian C Shaffer, Esperanza B Papadopoulos, Boglarka Gyurkocza, Miguel-Angel Perales, Omar Abdel-Wahab, Ross L Levine, Sergio A Giralt, Yanming Zhang, Wenbin Xiao, Nidhi Pai, Elli Papaemmanuil, Martin S Tallman, Mikhail Roshal, Aaron D Goldberg
Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT). Induction chemotherapy led to MRD- remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively...
January 2023: American Journal of Hematology
#53
JOURNAL ARTICLE
Yi-Jou Huang, Jia-Yu Chen, Ming Yan, Amanda G Davis, Sayuri Miyauchi, Liang Chen, Yajing Hao, Sigrid Katz, Rafael Bejar, Omar Abdel-Wahab, Xiang-Dong Fu, Dong-Er Zhang
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies with propensity to progress to acute myeloid leukemia (AML). Causal mutations in multiple classes of genes have been identified in MDS patients with some patients harboring more than one mutation. Interestingly, double mutations tend to occur in different classes, rather than the same class of genes, as exemplified by frequent co-occurring mutations in the transcription factor RUNX1 and the splicing factor SRSF2. This prototypic double mutant provides an opportunity to understand how their divergent functions in transcription and post-transcriptional regulation may be altered to jointly promote MDS...
October 7, 2022: Blood Advances
#54
MULTICENTER STUDY
Catherine C Coombs, John M Pagel, Nirav N Shah, Nicole Lamanna, Talha Munir, Ewa Lech-Maranda, Toby A Eyre, Jennifer A Woyach, William G Wierda, Chan Y Cheah, Jonathon B Cohen, Lindsey E Roeker, Manish R Patel, Bita Fakhri, Minal A Barve, Constantine S Tam, David Lewis, James N Gerson, Alvaro Alencar, Chaitra Ujjani, Ian Flinn, Suchitra Sundaram, Shuo Ma, Deepa Jagadeesh, Joanna Rhodes, Justin Taylor, Omar Abdel-Wahab, Paolo Ghia, Stephen J Schuster, Denise Wang, Binoj Nair, Edward Zhu, Donald E Tsai, Matthew S Davids, Jennifer R Brown, Wojciech Jurczak, Anthony R Mato
CONTEXT: Covalent BTK inhibitors (BTKi) have transformed the management of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), but many patients (pts) will require additional treatment. Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi that inhibits both wild type and C481-mutated BTK with equal low nM potency. OBJECTIVE: To evaluate the safety and efficacy of pirtobrutinib in previously treated CLL/SLL. DESIGN: BRUIN is a phase 1/2 multicenter study (NCT03740529) of oral pirtobrutinib monotherapy...
October 2022: Clinical Lymphoma, Myeloma & Leukemia
#55
JOURNAL ARTICLE
Anna S Nam, Neville Dusaj, Franco Izzo, Rekha Murali, Robert M Myers, Tarek H Mouhieddine, Jesus Sotelo, Salima Benbarche, Michael Waarts, Federico Gaiti, Sabrin Tahri, Ross Levine, Omar Abdel-Wahab, Lucy A Godley, Ronan Chaligne, Irene Ghobrial, Dan A Landau
Somatic mutations in cancer genes have been detected in clonal expansions across healthy human tissue, including in clonal hematopoiesis. However, because mutated and wild-type cells are admixed, we have limited ability to link genotypes with phenotypes. To overcome this limitation, we leveraged multi-modality single-cell sequencing, capturing genotype, transcriptomes and methylomes in progenitors from individuals with DNMT3A R882 mutated clonal hematopoiesis. DNMT3A mutations result in myeloid over lymphoid bias, and an expansion of immature myeloid progenitors primed toward megakaryocytic-erythroid fate, with dysregulated expression of lineage and leukemia stem cell markers...
October 2022: Nature Genetics
#56
JOURNAL ARTICLE
Matthew T Witkowski, Soobeom Lee, Eric Wang, Anna K Lee, Alexis Talbot, Chao Ma, Nikolaos Tsopoulidis, Justin Brumbaugh, Yaqi Zhao, Kathryn G Roberts, Simon J Hogg, Sofia Nomikou, Yohana E Ghebrechristos, Palaniraja Thandapani, Charles G Mullighan, Konrad Hochedlinger, Weiqiang Chen, Omar Abdel-Wahab, Justin Eyquem, Iannis Aifantis
B cell progenitor acute lymphoblastic leukemia (B-ALL) treatment has been revolutionized by T cell-based immunotherapies-including chimeric antigen receptor T cell therapy (CAR-T) and the bispecific T cell engager therapeutic, blinatumomab-targeting surface glycoprotein CD19. Unfortunately, many patients with B-ALL will fail immunotherapy due to 'antigen escape'-the loss or absence of leukemic CD19 targeted by anti-leukemic T cells. In the present study, we utilized a genome-wide CRISPR-Cas9 screening approach to identify modulators of CD19 abundance on human B-ALL blasts...
October 2022: Nature Immunology
#57
JOURNAL ARTICLE
Shivani Handa, Jeong-Ok Lee, Andriy Derkach, Richard M Stone, Alan Saven, Jessica K Altman, Michael R Grever, Kanti R Rai, Madhulika Shukla, Shreya Vemuri, Skye Montoya, Justin Taylor, Omar Abdel-Wahab, Martin S Tallman, Jae H Park
Vemurafenib, an oral BRAF inhibitor, has demonstrated high response rates in relapsed/refractory (R/R) hairy cell leukemia (HCL). However, little is known about long-term outcomes and response to retreatment. Herein, we report the results of 36 patients with R/R HCL treated with vemurafenib from the United States arm of the phase 2 clinical trial (NCT01711632). The best overall response rate was 86%, including 33% complete response (CR) and 53% partial response (PR). After a median follow-up of 40 months, 21 of 31 responders (68%) experienced relapse with a median relapse-free survival (RFS) of 19 months (range, 12...
December 22, 2022: Blood
#58
JOURNAL ARTICLE
Anna Yeaton, Geraldine Cayanan, Sanam Loghavi, Igor Dolgalev, Emmett M Leddin, Christian E Loo, Hedieh Torabifard, Deedra Nicolet, Jingjing Wang, Kate Corrigan, Varvara Paraskevopoulou, Daniel T Starczynowski, Eric Wang, Omar Abdel-Wahab, Aaron D Viny, Richard M Stone, John C Byrd, Olga A Guryanova, Rahul M Kohli, G Andrés Cisneros, Aristotelis Tsirigos, Ann-Kathrin Eisfeld, Iannis Aifantis, Maria Guillamot
UNLABELLED: Clonal hematopoiesis (CH) is an aging-associated condition characterized by the clonal outgrowth of mutated preleukemic cells. Individuals with CH are at an increased risk of developing hematopoietic malignancies. Here, we describe a novel animal model carrying a recurrent TET2 missense mutation frequently found in patients with CH and leukemia. In a fashion similar to CH, animals show signs of disease late in life when they develop a wide range of myeloid neoplasms, including acute myeloid leukemia (AML)...
October 5, 2022: Cancer Discovery
#59
JOURNAL ARTICLE
Sisi Chen, Rahul S Vedula, Antonio Cuevas-Navarro, Bin Lu, Simon J Hogg, Eric Wang, Salima Benbarche, Katherine Knorr, Won Jun Kim, Robert F Stanley, Hana Cho, Caroline Erickson, Michael Singer, Dan Cui, Steven Tittley, Benjamin H Durham, Tatiana S Pavletich, Elise Fiala, Michael F Walsh, Daichi Inoue, Sebastien Monette, Justin Taylor, Neal Rosen, Frank McCormick, R Coleman Lindsley, Pau Castel, Omar Abdel-Wahab
Recently, screens for mediators of resistance to FLT3 and ABL kinase inhibitors in leukemia resulted in the discovery of LZTR1 as an adaptor of a Cullin-3 RING E3 ubiquitin ligase complex responsible for degradation of RAS GTPases. In parallel, dysregulated LZTR1 expression via aberrant splicing and mutations were identified in clonal hematopoietic conditions. Here we identify that loss of LZTR1, or leukemia-associated mutants in the LZTR1 substrate and RAS GTPase RIT1 which escape degradation, drive hematopoietic stem cell (HSC) expansion and leukemia in vivo...
July 29, 2022: Cancer Discovery
#60
JOURNAL ARTICLE
Gaith Rjoub, Omar Abdel Wahab, Jamal Bentahar, Robin Cohen, Ahmed Saleh Bataineh
In the context of distributed machine learning, the concept of federated learning (FL) has emerged as a solution to the privacy concerns that users have about sharing their own data with a third-party server. FL allows a group of users (often referred to as clients ) to locally train a single machine learning model on their devices without sharing their raw data. One of the main challenges in FL is how to select the most appropriate clients to participate in the training of a certain task. In this paper, we address this challenge and propose a trust-based deep reinforcement learning approach to select the most adequate clients in terms of resource consumption and training time...
July 18, 2022: Information Systems Frontiers: a Journal of Research and Innovation
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