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John Byrd

Fiona C Brown, Paolo Cifani, Esther Drill, Jie He, Eric Still, Shan Zhong, Sohail Balasubramanian, Dean Pavlick, Bahar Yilmazel, Kristina M Knapp, Todd A Alonzo, Soheil Meshinchi, Richard M Stone, Steven M Kornblau, Guido Marcucci, Alan S Gamis, John C Byrd, Mithat Gonen, Ross L Levine, Alex Kentsis
Cure rates of children and adults with acute myeloid leukaemia (AML) remain unsatisfactory partly due to chemotherapy resistance. We investigated the genetic basis of AML in 107 primary cases by sequencing 670 genes mutated in haematological malignancies. SETBP1, ASXL1 and RELN mutations were significantly associated with primary chemoresistance. We identified genomic alterations not previously described in AML, together with distinct genes that were significantly overexpressed in therapy-resistant AML. Defined gene mutations were sufficient to explain primary induction failure in only a minority of cases...
October 21, 2016: British Journal of Haematology
Zijun Y Xu-Monette, Ling Li, John C Byrd, Kausar J Jabbar, Ganiraju C Manyam, Charlotte Maria de Winde, Michiel van den Brand, Alexandar Tzankov, Carlo Visco, Jing Wang, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L Richards, Eric D Hsi, William W L Choi, Jooryung Huh, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Ben M Parsons, Jane N Winter, Michael Wang, Fredrick B Hagemeister, Miguel A Piris, J Han van Krieken, L Jeffrey Medeiros, Yong Li, Annemiek B van Spriel, Ken H Young
CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B-cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. In this study, we assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its clinical and biologic significance in 773 patients treated with rituximab-CHOP and 231 patients treated with CHOP chemotherapy. We found CD37 loss (CD37(-)) in ~60% of DLBCL predicted significantly decreased survival rates in R-CHOP-treated patients, independent of the International Prognostic Index (IPI), germinal-center-B-cell-like (GCB)/activated-B-cell-like (ABC) cell-of-origin, nodal/extranodal primary origin, and the prognostic factors associated with CD37(-), including TP53 mutation, NF-κB(high), Myc(high), p-STAT3(high), survivin(high), p63(-), and BCL6 translocation...
October 19, 2016: Blood
Prashant Trikha, Robert L Plews, Andrew Stiff, Shalini Gautam, Vincent Hsu, David Abood, Robert Wesolowski, Ian Landi, Xiaokui Mo, John Phay, Ching-Shih Chen, John Byrd, Michael Caligiuri, Susheela Tridandapani, William Carson
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of early myeloid cells that accumulate in the blood and tumors of patients with cancer. MDSC play a critical role during tumor evasion and promote immune suppression through variety of mechanisms, such as the generation of reactive oxygen and nitrogen species (ROS and RNS) and cytokines. AMPactivated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that regulates energy homeostasis and metabolic stress. However, the role of AMPK in the regulation of MDSC function remains largely unexplored...
2016: Oncoimmunology
Arianna Bottoni, Lara Rizzotto, Tzung-Huei Lai, Chaomei Liu, Lisa L Smith, Rose Mantel, Sean Reiff, Dalia El-Gamal, Karilyn Larkin, Amy J Johnson, Rosa Lapalombella, Amy Lehman, William Plunkett, John C Byrd, James S Blachly, Jennifer A Woyach, Deepa Sampath
BTK is a critical mediator of survival in B cell neoplasms. While BTK inhibitors have transformed therapy in CLL, high genetic risk patients are at risk for relapse and have a poor prognosis. Identification of novel therapeutic strategies for this group of patients is an urgent unmet clinical need, and therapies that target BTK via alternative mechanisms may fill this niche. Herein, we identify a set of miRNAs that target BTK in primary CLL cells and show that the HDAC repressor complex is recruited to these miRNA promoters to silence their expression...
October 17, 2016: Blood
Shuai Dong, John C Byrd
The role of Lyn, both a positive and a negative regulator of B and myeloid cells, in chronic lymphocytic leukemia (CLL) has not been well characterized. In this issue of Cancer Cell, Nguyen et al. demonstrated that Lyn in macrophages rather than in CLL cells is critical for the malignancy.
October 10, 2016: Cancer Cell
Ingo G H Schmidt-Wolf, Christoph Plass, John C Byrd, Kathrin Frevel, Torsten Pietsch, Andreas Waha
BACKGROUND: Chronic lymphocytic leukemia (CLL) is characterized by a clonal accumulation of neoplastic lymphocytes, indicating disruption of apoptosis. PATIENTS AND METHODS: Differential methylation hybridization analysis was performed to identify novel target genes silenced by CpG island methylation in patients with CLL. RESULTS: Patched (PTCH), a tumor-suppressor gene, was found to be frequently methylated in CLL samples compared to samples derived from healthy individuals...
September 2016: Anticancer Research
Steven M Horwitz, Andrew D Zelenetz, Leo I Gordon, William G Wierda, Jeremy S Abramson, Ranjana H Advani, C Babis Andreadis, Nancy Bartlett, John C Byrd, Luis E Fayad, Richard I Fisher, Martha J Glenn, Thomas M Habermann, Nancy Lee Harris, Francisco Hernandez-Ilizaliturri, Richard T Hoppe, Mark S Kaminski, Christopher R Kelsey, Youn H Kim, Susan Krivacic, Ann S LaCasce, Matthew Lunning, Auayporn Nademanee, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Kenneth Roberts, Ayman A Saad, Lubomir Sokol, Lode J Swinnen, Julie M Vose, Joachim Yahalom, Nadeem Zafar, Mary Dwyer, Hema Sundar, Pierluigi Porcu
Peripheral T-cell lymphomas (PTCLs) represent a relatively uncommon heterogeneous group of non-Hodgkin's lymphomas (NHLs) with an aggressive clinical course and poor prognosis. Anthracycline-based multiagent chemotherapy with or without radiation therapy followed by first-line consolidation with high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) is the standard approach to most of the patients with newly diagnosed PTCL. Relapsed or refractory disease is managed with second-line systemic therapy followed by HDT/ASCR or allogeneic stem cell transplant, based on the patient's eligibility for transplant...
September 2016: Journal of the National Comprehensive Cancer Network: JNCCN
Eleshia J Morrison, Joseph M Flynn, Jeffrey Jones, John C Byrd, Barbara L Andersen
Chronic lymphocytic leukemia (CLL) is an incurable illness, with some patients requiring no treatment until disease progression. Burden from physical symptoms has been associated with depression, anxiety, and stress in cancer patients. Additionally, patient factors, i.e., individual differences, have been associated with worse psychological outcomes. There are few psychological studies of CLL, with no examination of individual differences. A cross-sectional design studied the covariation of symptom burden with depressive and anxiety symptoms and cancer-specific stress, and tested patients' individual differences as predictors and as moderators...
August 19, 2016: Annals of Hematology
Bhavana Bhatnagar, Ann-Kathrin Eisfeld, Deedra Nicolet, Krzysztof Mrózek, James S Blachly, Shelley Orwick, David M Lucas, Jessica Kohlschmidt, William Blum, Jonathan E Kolitz, Richard M Stone, Clara D Bloomfield, John C Byrd
Somatic mutation of the DNMT3A gene at the arginine R882 site is common in acute myeloid leukaemia (AML). The prognostic significance of DNMT3A R882 mutation clearance, using traditional diagnostic next generation sequencing (NGS) methods, during complete remission (CR) in AML patients is controversial. We examined the impact of clearing DNMT3A R882 mutations at diagnosis to the detectable threshold of ˂3% during CR on outcome in 56 adult AML patients. Mutational remission, defined as clearance of pre-treatment DNMT3A R882 and all other AML-associated mutations to a variant allele frequency ˂3%, occurred in 14 patients whereas persistent DNMT3A R882 mutations were observed in 42 patients...
October 2016: British Journal of Haematology
Gayathri Natarajan, Steve Oghumu, Cesar Terrazas, Sanjay Varikuti, John C Byrd, Abhay R Satoskar
Ibrutinib, a BTK inhibitor, is currently used to treat various hematological malignancies. We evaluated whether ibrutinib treatment during development of murine bone marrow-derived dendritic cells (DCs) modulates their maturation and activation. Ibrutinib treatment increased the proportion of CD11c(+) DCs, upregulated the expression of MHC-II and CD80 and downregulated Ly6C expression by DCs. Additionally, ibrutinib treatment led to an increase in MHC-II(+), CD80(+) and CCR7(+) DCs but a decrease in CD86(+) DCs upon LPS stimulation...
June 2016: Oncoimmunology
Christian Niederwieser, Deedra Nicolet, Andrew J Carroll, Jonathan E Kolitz, Bayard L Powell, Jessica Kohlschmidt, Richard M Stone, John C Byrd, Krzysztof Mrózek, Clara D Bloomfield
Achievement of complete remission is essential for long-term survival of acute myeloid leukemia patients. We evaluated the prognostic significance of cytogenetics at complete remission in 258 adults with de novo acute myeloid leukemia and abnormal pretreatment karyotypes, treated on Cancer and Leukemia Group B front-line studies, with cytogenetic data at onset of morphologic complete remission. Thirty-two patients had abnormal karyotypes at time of initial complete remission (28 had ≥1 abnormalities seen pretreatment, and four acute myeloid leukemia-related abnormalities not detected pretreatment); 226 patients had normal remission karyotypes...
July 28, 2016: Haematologica
Bonnie K Harrington, Heather L Gardner, Raquel Izumi, Ahmed Hamdy, Wayne Rothbaum, Kevin R Coombes, Todd Covey, Allard Kaptein, Michael Gulrajani, Bart Van Lith, Cecile Krejsa, Christopher C Coss, Duncan S Russell, Xiaoli Zhang, Bridget K Urie, Cheryl A London, John C Byrd, Amy J Johnson, William C Kisseberth
Acalabrutinib (ACP-196) is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK) with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL). First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells...
2016: PloS One
Jason N Byrd, Jesse J Lutz, Yifan Jin, Duminda S Ranasinghe, John A Montgomery, Ajith Perera, Xiaofeng F Duan, Larry W Burggraf, Beverly A Sanders, Rodney J Bartlett
The accurate determination of the preferred Si12C12 isomer is important to guide experimental efforts directed towards synthesizing SiC nano-wires and related polymer structures which are anticipated to be highly efficient exciton materials for the opto-electronic devices. In order to definitively identify preferred isomeric structures for silicon carbon nano-clusters, highly accurate geometries, energies, and harmonic zero point energies have been computed using coupled-cluster theory with systematic extrapolation to the complete basis limit for set of silicon carbon clusters ranging in size from SiC3 to Si12C12...
July 14, 2016: Journal of Chemical Physics
Ian W Flinn, Amy S Ruppert, William Harwin, David Waterhouse, Steven Papish, Jeffrey A Jones, John Hainsworth, John C Byrd
Despite the recent advances in treatment of CLL with targeted agents such as ibrutinib, availability of nonchemotherapy based therapies is desired. Given the 58% response rate (1996 NCI-WG criteria) of single agent ofatumumab in CLL refractory to fludarabine and alemtuzumab, we initiated a phase II trial examining response, safety, and progression-free survival (PFS) of ofatumumab as front-line monotherapy. Patients enrolled included untreated, symptomatic CLL patients over the age of 65 or those who were inappropriate/did not desire chemotherapy...
October 2016: American Journal of Hematology
Terrell C Lloyd, Matthew C Allender, Grace Archer, Christopher A Phillips, John Byrd, A Russell Moore
Box turtles are long-lived, inhabit both aquatic and terrestrial habitats, and have relatively small home ranges making them a suitable candidate as a sentinel. To characterize their changes in response to environmental health, assessment of observed variation of this species is required. Thus, a comparative health assessment was employed in 825 Eastern box turtles in east central Illinois and Oak Ridge, Tennessee, to establish a baseline health assessment with regard to sex, age class, season, and location, identify temporal trends, and map parameters...
July 6, 2016: EcoHealth
Alicia K Byrd, Boris L Zybailov, Leena Maddukuri, Jun Gao, John C Marecki, Mihir Jaiswal, Matthew R Bell, Wezley C Griffin, Megan R Reed, Shubeena Chib, Samuel G Mackintosh, Angus M MacNicol, Giulia Baldini, Robert L Eoff, Kevin D Raney
Cells engage numerous signaling pathways in response to oxidative stress that together repair macromolecular damage or direct the cell toward apoptosis. As a result of DNA damage, mitochondrial DNA or nuclear DNA has been shown to enter the cytoplasm where it binds to "DNA sensors," which in turn initiate signaling cascades. Here we report data that support a novel signaling pathway in response to oxidative stress mediated by specific guanine-rich sequences that can fold into G-quadruplex DNA (G4DNA). In response to oxidative stress, we demonstrate that sequences capable of forming G4DNA appear at increasing levels in the cytoplasm and participate in assembly of stress granules...
August 19, 2016: Journal of Biological Chemistry
Daryl R Chastain, John L Snider, John S Choinski, Guy D Collins, Calvin D Perry, Jared Whitaker, Timothy L Grey, Ronald B Sorensen, Marc van Iersel, Seth A Byrd, Wesley Porter
Temperature and drought are major abiotic limitations to crop productivity worldwide. While abiotic stress physiology research has focused primarily on fully expanded leaves, no studies have investigated photosynthetic tolerance to concurrent drought and high temperature during leaf ontogeny. To address this, Gossypium hirsutum plants were exposed to five irrigation treatments, and two different leaf stages were sampled on three dates during an abnormally dry summer. Early in the growing season, ontogenic PSII heat tolerance differences were observed...
May 12, 2016: Journal of Plant Physiology
Rebekah L Browning, William H Byrd, Nikhil Gupta, Jeffrey Jones, Xiaokui Mo, Erin Hertlein, Lianbo Yu, Natarajan Muthusamy, John C Byrd
The immunomodulatory drug lenalidomide has demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL), despite a lack of direct cytotoxic effects in vitro The mechanism of lenalidomide efficacy in vivo is thought to occur via a combination of enhanced immune activity and an alteration of tumor cell-microenvironment interactions. We demonstrate in whole blood from patients with CLL that lenalidomide significantly depletes malignant B cells. Lenalidomide also induced production of interleukin-21 (IL21) and its mRNA in T cells from patients with CLL...
August 2016: Cancer Immunology Research
Holly N Cukier, Brian W Kunkle, Badri N Vardarajan, Sophie Rolati, Kara L Hamilton-Nelson, Martin A Kohli, Patrice L Whitehead, Beth A Dombroski, Derek Van Booven, Rosalyn Lang, Derek M Dykxhoorn, Lindsay A Farrer, Michael L Cuccaro, Jeffery M Vance, John R Gilbert, Gary W Beecham, Eden R Martin, Regina M Carney, Richard Mayeux, Gerard D Schellenberg, Goldie S Byrd, Jonathan L Haines, Margaret A Pericak-Vance
OBJECTIVE: To identify a causative variant(s) that may contribute to Alzheimer disease (AD) in African Americans (AA) in the ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene, a known risk factor for late-onset AD. METHODS: Custom capture sequencing was performed on ∼150 kb encompassing ABCA7 in 40 AA cases and 37 AA controls carrying the AA risk allele (rs115550680). Association testing was performed for an ABCA7 deletion identified in large AA data sets (discovery n = 1,068; replication n = 1,749) and whole exome sequencing of Caribbean Hispanic (CH) AD families...
June 2016: Neurology. Genetics
Shalini Gautam, Kavin Fatehchand, Saranya Elavazhagan, Brenda F Reader, Li Ren, Xiaokui Mo, John C Byrd, Susheela Tridandapani, Jonathan P Butchar
Nurse-like cells (NLCs) play a central role in chronic lymphocytic leukemia (CLL) because they promote the survival and proliferation of CLL cells. NLCs are derived from the monocyte lineage and are driven toward their phenotype via contact-dependent and -independent signals from CLL cells. Because of the central role of NLCs in promoting disease, new strategies to eliminate or reprogram them are needed. Successful reprogramming may be of extra benefit because NLCs express Fcγ receptors (FcγRs) and thus could act as effector cells within the context of antibody therapy...
July 1, 2016: Journal of Biological Chemistry
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