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https://www.readbyqxmd.com/read/28323261/corrigendum-ubiquitination-of-hnrnpa1-by-traf6-links-chronic-innate-immune-signaling-with-myelodysplasia
#1
Jing Fang, Lyndsey C Bolanos, Kwangmin Choi, Xiaona Liu, Susanne Christie, Shailaja Akunuru, Rupali Kumar, Dehua Wang, Xiaoting Chen, Kenneth D Greis, Peter Stoilov, Marie-Dominique Filippi, Jaroslaw P Maciejewski, Guillermo Garcia-Manero, Matthew T Weirauch, Nathan Salamonis, Hartmut Geiger, Yi Zheng, Daniel T Starczynowski
No abstract text is available yet for this article.
March 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28278723/phase-ii-trial-of-homoharringtonine-with-imatinib-in-chronic-accelerated-and-blast-phase-chronic-myeloid-leukemia
#2
Abhishek Maiti, Jorge Cortes, Alessandra Ferrajoli, Zeev Estrov, Gautam Borthakur, Guillermo Garcia-Manero, Elias Jabbour, Farhad Ravandi, Susan O'Brien, Hagop Kantarjian
No abstract text is available yet for this article.
February 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28270436/focal-adhesion-kinase-as-a-potential-target-in-aml-and-mds
#3
Bing Z Carter, Po Yee Mak, Xiangmeng Wang, Hui Yang, Guillermo Garcia-Manero, Duncan Mak, Hong Mu, Vivian Ruvolo, Yihua Qiu, Kevin Coombes, Nianxiang Zhang, Brittany Ragon, David T Weaver, Jonathan A Pachter, Steven Kornblau, Michael Andreeff
Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics (P = 2 x 10-4) and relapse (P = 0...
March 7, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28246192/greater-than-one-tp53-abnormality-is-a-dominant-characteristic-of-pure-erythroid-leukemia
#4
Guillermo Montalban-Bravo, Christopher B Benton, Sa A Wang, Farhad Ravandi, Tapan Kadia, Jorge Cortes, Naval Daver, Koichi Takahashi, Courtney DiNardo, Elias Jabbour, Gautam Borthakur, Marina Konopleva, Sherry Pierce, Carlos Bueso-Ramos, Keyur Patel, Steven Kornblau, Hagop Kantarjian, Ken H Young, Guillermo Garcia-Manero, Michael Andreeff
No abstract text is available yet for this article.
February 28, 2017: Blood
https://www.readbyqxmd.com/read/28242540/relation-between-chelation-and-clinical-outcomes-in-lower-risk-patients-with-myelodysplastic-syndromes-registry-analysis-at-5-years
#5
REVIEW
Roger M Lyons, Billie J Marek, Carole Paley, Jason Esposito, Katie McNamara, Paul D Richards, Nicholas DiBella, Guillermo Garcia-Manero
Prospective data are needed to ascertain the impact of iron chelation therapy in patients with myelodysplastic syndromes. The present 5-year prospective registry analysis was conducted to compare clinical outcomes between chelated and nonchelated patients with lower-risk myelodysplastic syndromes and transfusional iron overload. In an interim analysis at 24 months, we previously reported that chelation therapy was associated with longer median overall survival and a tendency toward longer leukemia-free survival and fewer cardiac events...
January 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28236110/shear-induced-structural-and-thermodynamic-phase-transitions-in-micellar-systems
#6
Angelina Martín Del Campo, J Paulo García-Sandoval, J F Armando Soltero, Fernando Bautista, Octavio Manero, Jorge E Puig
In this contribution a methodology to compute and classify shear-induced structural and phase transitions in surfactant/water mixtures from rheological measurements is presented. Non-linear rheological experiments, considering variations in surfactant concentration and temperature, are analyzed. In particular, the parameters of the BMP (Bautista-Manero-Puig) model, obtained from the fitting of the shear stress versus shear rate data, which are functions of surfactant concentration and temperature, allow classifying structural and phase transition boundaries...
February 2017: European Physical Journal. E, Soft Matter
https://www.readbyqxmd.com/read/28194038/itd-mutation-in-flt3-tyrosine-kinase-promotes-warburg-effect-and-renders-therapeutic-sensitivity-to-glycolytic-inhibition
#7
H-Q Ju, G Zhan, A Huang, Y Sun, S Wen, J Yang, W-H Lu, R-H Xu, J Li, Y Li, G Garcia-Manero, P Huang, Y Hu
Internal tandem duplication (ITD) mutation in Fms-like tyrosine kinase 3 gene (FLT3/ITD) represents an unfavorable genetic change in acute myeloid leukemia (AML) and is associated with poor prognosis. Metabolic alterations have been involved in tumor progression and attracted interest as a target for therapeutic intervention. However, few studies analyzed the adaptations of cellular metabolism in the context of FLT3/ITD mutation. Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28111463/comparison-of-clinical-outcomes-and-prognostic-utility-of-risk-stratification-tools-in-patients-with-therapy-related-vs-de-novo-myelodysplastic-syndromes-a-report-on-behalf-of-the-mds-clinical-research-consortium
#8
A M Zeidan, N Al Ali, J Barnard, E Padron, J E Lancet, M A Sekeres, D P Steensma, A DeZern, G Roboz, E Jabbour, G Garcia-Manero, A List, R Komrokji
While therapy-related (t)-myelodysplastic syndromes (MDS) have worse outcomes than de novo MDS (d-MDS), some t-MDS patients have an indolent course. Most MDS prognostic models excluded t-MDS patients during development. The performances of the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), MD Anderson Global Prognostic System (MPSS), WHO Prognostic Scoring System (WPSS) and t-MDS Prognostic System (TPSS) were compared among patients with t-MDS. Akaike information criteria (AIC) assessed the relative goodness of fit of the models...
February 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28094841/phase-2-randomized-double-blind-study-of-pracinostat-in-combination-with-azacitidine-in-patients-with-untreated-higher-risk-myelodysplastic-syndromes
#9
Guillermo Garcia-Manero, Guillermo Montalban-Bravo, Jesus G Berdeja, Yasmin Abaza, Elias Jabbour, James Essell, Roger M Lyons, Farhad Ravandi, Michael Maris, Brian Heller, Amy E DeZern, Sunil Babu, David Wright, Bertrand Anz, Ralph Boccia, Rami S Komrokji, Philip Kuriakose, James Reeves, Mikkael A Sekeres, Hagop M Kantarjian, Richard Ghalie, Gail J Roboz
BACKGROUND: The prognosis of patients with higher risk myelodysplastic syndromes (MDS) remains poor despite available therapies. Histone deacetylase inhibitors have demonstrated activity in patients with MDS and in vitro synergy with azacitidine. METHODS: A phase 2 randomized, placebo-controlled clinical trial of azacitidine and pracinostat was conducted in patients who had International Prognostic Scoring System intermediate-2-risk or high-risk MDS. The primary endpoint was the complete response (CR) rate by cycle 6 of therapy...
January 17, 2017: Cancer
https://www.readbyqxmd.com/read/28089328/usefulness-of-three-dimensional-transthoracic-echocardiograhy-in-the-localization-of-the-micra-leadless-pacemaker
#10
José Luis Martínez-Sande, Carlos Peña-Gil, Javier García-Seara, Moisés Rodríguez-Mañero, María Amparo Martínez-Monzonis, José Ramón González-Juanatey
No abstract text is available yet for this article.
January 11, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28076892/impact-of-achievement-of-complete-cytogenetic-response-on-outcome-in-patients-with-myelodysplastic-syndromes-treated-with-hypomethylating-agents
#11
Elias Jabbour, Paolo Strati, Monica Cabrero, Susan O'Brien, Farhad Ravandi, Carlos Bueso-Ramos, Qiao Wei, Jianhua Hu, Simon Abi Aad, Nicholas J Short, Courtney Dinardo, Naval Daver, Tapan Kadia, William Wierda, Yue Wei, Simona Colla, Gautam Borthakur, Jorge Cortes, Zeev Estrov, Hagop Kantarjian, Guillermo Garcia-Manero
Two hundred and sixteen consecutive patients with MDS and abnormal karyotype treated with hypomethylating agents between 4/04 and 10/12 were reviewed. Median follow-up was 17 months. Using IWG criteria, best responses were complete response (CR) in 79 patients (37%), partial response (PR) in 4 (2%), and hematologic improvement (HI) in 10 (5%). Cytogenetic response (CyR) was achieved in 78 patients (36%): complete (CCyR) in 62 (29%) and partial in 16 (7%). CyR was achieved in 48 of 79 patients (61%) with CR, 1 of 14 (7%) with PR/HI, and in 29 of the 123 (24%) with no morphologic response...
April 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28052371/significance-of-recurrence-of-minimal-residual-disease-detected-by-multi-parameter-flow-cytometry-in-patients-with-acute-lymphoblastic-leukemia-in-morphological-remission
#12
Naveen Pemmaraju, Hagop Kantarjian, Jeffrey L Jorgensen, Elias Jabbour, Nitin Jain, Deborah Thomas, Susan O'Brien, Xuemei Wang, Xuelin Huang, Sa A Wang, Marina Konopleva, Sergej Konoplev, Tapan Kadia, Rebecca Garris, Sherry Pierce, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi
We sought to determine the significance of minimal residual disease (MRD) relapse in patients with ALL after achieving MRD negative status following induction and consolidation therapy. Between January 2003 and September 2014, 647 newly diagnosed patients were treated [HyperCVAD-based (n = 531); Augmented BFM (n = 116)]. Six hundred and one (93%) achieved complete remission (CR), and 546 (91%) became MRD negative. Fifty-five patients [HyperCVAD-based (n = 49); Augmented BFM (n = 6)] developed recurrence of MRD while still in morphological CR and are the subjects of this study...
March 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28040720/myelodysplastic-syndromes-version-2-2017-nccn-clinical-practice-guidelines-in-oncology
#13
Peter L Greenberg, Richard M Stone, Aref Al-Kali, Stefan K Barta, Rafael Bejar, John M Bennett, Hetty Carraway, Carlos M De Castro, H Joachim Deeg, Amy E DeZern, Amir T Fathi, Olga Frankfurt, Karin Gaensler, Guillermo Garcia-Manero, Elizabeth A Griffiths, David Head, Ruth Horsfall, Robert A Johnson, Mark Juckett, Virginia M Klimek, Rami Komrokji, Lisa A Kujawski, Lori J Maness, Margaret R O'Donnell, Daniel A Pollyea, Paul J Shami, Brady L Stein, Alison R Walker, Peter Westervelt, Amer Zeidan, Dorothy A Shead, Courtney Smith
The myelodysplastic syndromes (MDS) comprise a heterogenous group of myeloid disorders with a highly variable disease course. Diagnostic criteria to better stratify patients with MDS continue to evolve, based on morphology, cytogenetics, and the presence of cytopenias. More accurate classification of patients will allow for better treatment guidance. Treatment encompasses supportive care, treatment of anemia, low-intensity therapy, and high-intensity therapy. This portion of the guidelines focuses on diagnostic classification, molecular abnormalities, therapeutic options, and recommended treatment approaches...
January 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28040461/the-micra-leadless-transcatheter-pacemaker-implantation-and-mid-term-follow-up-results-in-a-single-center
#14
José Luis Martínez-Sande, Javier García-Seara, Moisés Rodríguez-Mañero, Xesús Alberte Fernández-López, Laila González-Melchor, Alfredo Redondo-Diéguez, Rocío González-Ferreiro, José Ramón González-Juanatey
INTRODUCTION AND OBJECTIVES: Currently, studies on the leadless pacemaker (Micra) have mostly been limited to clinical trials with less than 6 months' follow-up and they often fail to reflect real population outcomes. We sought to evaluate electrical parameters at implantation and chronologically during follow-up, as well as the safety of this new technique. METHODS: This prospective, observational study included 30 consecutive patients, all ≥ 65 years, with an indication for single-chamber pacemaker implantation...
December 28, 2016: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28038805/nutritional-status-is-related-to-heart-failure-severity-and-hospital-readmissions-in-acute-heart-failure
#15
Rosa María Agra Bermejo, Rocío González Ferreiro, Alfonso Varela Román, Inés Gómez Otero, Omar Kreidieh, Patricia Conde Sabarís, Moisés Rodríguez-Mañero, María Moure González, Ana Seoane Blanco, Alejandro Virgós Lamela, Alberto García Castelo, Jose Ramón González Juanatey
BACKGROUND: Malnutrition is common in hospitalized heart failure (HF) patients and predicts adverse outcomes. The relationship between nutritional status and outcomes in HF has been partially studied. Our aim was to determine the relationship between the nutritional status and the long-term prognosis in patients hospitalized for acute HF. METHODS: We analyzed 145 patients admitted consecutively to a cardiology department for acute HF. Nutritional status was measured with the CONUT method, a validated scale based on laboratory testing (albumin; cholesterol; lymphocytes) during hospitalization...
March 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28029524/-external-lumbar-drainage-with-volumetric-continuing-infusion-pump-in-patients-with-cerebrospinal-fluid-leak-a-case-series
#16
Ana Belén Manso Melgosa, Helena García Gutiérrez, Mónica Fernández Porras, Ana Berta Castrillo Manero, Belén Pérez Marijuán
OBJECTIVE: To describe the incidence and complications arising in a number of cases of patients with cerebrospinal fluid leak treated by external lumbar drainage with infusion pump (IP) volumetric continuous from 2001 to 2014. Quantify cerebrospinal fluid leak closed by lumbar drainage with IP. METHODS: Retrospective descriptive case series study. POPULATION: patients undergoing transsphenoidal pituitary surgery, Chiari surgery and laminectomy, that developed postoperative cerebrospinal fluid leak treated with continuous external lumbar drainage by IP...
January 2017: Enfermería Clínica
https://www.readbyqxmd.com/read/28024152/ubiquitination-of-hnrnpa1-by-traf6-links-chronic-innate-immune-signaling-with-myelodysplasia
#17
Jing Fang, Lyndsey C Bolanos, Kwangmin Choi, Xiaona Liu, Susanne Christie, Shailaja Akunuru, Rupali Kumar, Dehua Wang, Xiaoting Chen, Kenneth D Greis, Peter Stoilov, Marie-Dominique Filippi, Jaroslaw P Maciejewski, Guillermo Garcia-Manero, Matthew T Weirauch, Nathan Salomonis, Hartmut Geiger, Yi Zheng, Daniel T Starczynowski
Toll-like receptor (TLR) activation contributes to premalignant hematologic conditions, such as myelodysplastic syndromes (MDS). TRAF6, a TLR effector with ubiquitin (Ub) ligase activity, is overexpressed in MDS hematopoietic stem/progenitor cells (HSPCs). We found that TRAF6 overexpression in mouse HSPC results in impaired hematopoiesis and bone marrow failure. Using a global Ub screen, we identified hnRNPA1, an RNA-binding protein and auxiliary splicing factor, as a substrate of TRAF6. TRAF6 ubiquitination of hnRNPA1 regulated alternative splicing of Arhgap1, which resulted in activation of the GTP-binding Rho family protein Cdc42 and accounted for hematopoietic defects in TRAF6-expressing HSPCs...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/28006851/poor-outcomes-associated-with-der-22-t-9-22-and-9-9p-in-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-receiving-chemotherapy-plus-a-tyrosine-kinase-inhibitor
#18
Nicholas J Short, Hagop M Kantarjian, Koji Sasaki, Farhad Ravandi, Heidi Ko, C Cameron Yin, Guillermo Garcia-Manero, Jorge E Cortes, Rebecca Garris, Susan M O'Brien, Keyur Patel, Maria Khouri, Deborah Thomas, Nitin Jain, Tapan M Kadia, Naval Daver, Christopher B Benton, Ghayas C Issa, Marina Konopleva, Elias Jabbour
In patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus a tyrosine kinase inhibitor (TKI), the prognostic impact of additional chromosomal abnormalities (ACAs) is not well-established. We evaluated the prognostic impact of individual ACAs in 152 patients with Ph+ ALL receiving first-line intensive chemotherapy plus either imatinib (n=36), dasatinib (n=74) or ponatinib (n=42). ACAs were identified in 118 patients (78%). Compared to outcomes of patients without ACAs, ACAs were not associated with differences in either relapse-free survival (RFS; P=0...
December 22, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/28003274/long-term-outcome-of-acute-promyelocytic-leukemia-treated-with-all-trans-retinoic-acid-arsenic-trioxide-and-gemtuzumab
#19
Yasmin Abaza, Hagop M Kantarjian, Guillermo Garcia-Manero, Elihu Estey, Gautam Borthakur, Elias Jabbour, Stefan Faderl, Susan O'Brien, William Wierda, Sherry Pierce, Mark Brandt, Deborah McCue, Rajyalakshmi Luthra, Keyur Patel, Steven Kornblau, Tapan Kadia, Naval Daver, Courtney DiNardo, Nitin Jain, Srdan Verstovsek, Alessandra Ferrajoli, Michael Andreeff, Marina Konopleva, Zeev Estrov, Maria Foudray, David McCue, Jorge Cortes, Farhad Ravandi
The combination of all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard risk newly diagnosed patients with acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamycin (GO) in high-risk patients. We examined the long-term outcome of newly diagnosed APL patients treated at our institution on three consecutive prospective clinical trials using the combination of ATRA, ATO, with or without GO...
December 21, 2016: Blood
https://www.readbyqxmd.com/read/27923552/preleukaemic-clonal-haemopoiesis-and-risk-of-therapy-related-myeloid-neoplasms-a-case-control-study
#20
Koichi Takahashi, Feng Wang, Hagop Kantarjian, Denaha Doss, Kanhav Khanna, Erika Thompson, Li Zhao, Keyur Patel, Sattva Neelapu, Curtis Gumbs, Carlos Bueso-Ramos, Courtney D DiNardo, Simona Colla, Farhad Ravandi, Jianhua Zhang, Xuelin Huang, Xifeng Wu, Felipe Samaniego, Guillermo Garcia-Manero, P Andrew Futreal
BACKGROUND: Therapy-related myeloid neoplasms are secondary malignancies that are often fatal, but their risk factors are not well understood. Evidence suggests that individuals with clonal haemopoiesis have increased risk of developing haematological malignancies. We aimed to identify whether patients with cancer who have clonal haemopoiesis are at an increased risk of developing therapy-related myeloid neoplasms. METHODS: We did this retrospective case-control study to compare the prevalence of clonal haemopoiesis between patients treated for cancer who later developed therapy-related myeloid neoplasms (cases) and patients who did not develop these neoplasms (controls)...
January 2017: Lancet Oncology
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