Roy Sylvie, Karim Ghani, Pedro O de Campos-Lima, Manuel Caruso
In this study, we showed that a codon optimized version of the spike (S) protein of SARS-CoV-2 can migrate to the cell membrane. However, efficient production of Moloney murine leukemia (MLV) infectious viral particles was only achieved with stable expression of a shorter S version in C-terminal (ΔS) in MLV Gag-pol expressing cells. As compared to transient transfections, this platform generated viruses with a 1,000-fold higher titer. ΔS was 15-times more efficiently incorporated into VLPs as compared to S, and that was not due to steric interference between the cytoplasmic tail and the MLV capsid, as similar differences were also observed with extracellular vesicles...
January 19, 2021: Virus Research
Akshay Sharma, Neel S Bhatt, Andrew St Martin, Muhammad Bilal Abid, Jenni Bloomquist, Roy F Chemaly, Christopher Dandoy, Jordan Gauthier, Lohith Gowda, Miguel-Angel Perales, Stuart Seropian, Bronwen E Shaw, Eileen E Tuschl, Amer M Zeidan, Marcie L Riches, Gunjan L Shah
BACKGROUND: Haematopoietic stem-cell transplantation (HSCT) recipients are considered at high risk of poor outcomes after COVID-19 on the basis of their immunosuppressed status, but data from large studies in HSCT recipients are lacking. This study describes the characteristics and outcomes of HSCT recipients after developing COVID-19. METHODS: In response to the pandemic, the Center for International Blood and Marrow Transplant Research (CIBMTR) implemented a special form for COVID-19-related data capture on March 27, 2020...
January 19, 2021: Lancet Haematology
Hee Young Ju, Ji Won Lee, Hee Won Cho, Ju Kyung Hyun, Youngeun Ma, Eun Sang Yi, Keon Hee Yoo, Ki Woong Sung, Rihwa Choi, Hong Hoe Koo, Soo-Youn Lee
BACKGROUND: Large inter-individual variations in drug metabolism pose a challenge in determining 6-mercaptopurine (6MP) doses. As the last product of 6MP metabolism, DNA-thioguanine nucleotide (DNA-TGN) could reflect the efficacy of 6MP, especially in patients harboring variants in the 6MP metabolism pathway. The aim of this study was to investigate the clinical significance of DNA-TGN monitoring in Korean pediatric acute lymphoblastic leukemia (ALL) patients, focusing on the NUDT15 genotype...
2021: PloS One
Rongrong Li, Wenying Yao, Yuying Chan, Min Shen, Xin Wang, Fang Wen, Qi Yang
BACKGROUND: Children with acute leukemia experience various distressing symptoms due to the disease and its treatment during chemotherapy. These symptoms cluster together and have negative impacts on patient outcomes. OBJECTIVE: The aim of this study was to examine symptom clusters that children with acute leukemia undergoing chemotherapy are experiencing and the impact of these symptom clusters on their quality of life. METHODS: A cross-sectional study design was used, and 184 Chinese children with acute leukemia who were undergoing chemotherapy were invited to participate in the study...
January 20, 2021: Cancer Nursing
Jing Qi, Fan Zhang, Yinhua Liu, Junping Yao, Youhai Xu, Hesheng He
Extramedullary blast crisis of chronic myeloid leukemia (CML) is defined as extramedullary disease composed of blasts regardless of the proliferation of blasts in the bone marrow. The commonly affected sites are the lymph node, central nervous system, bone, skin, and soft tissue. However, skin infiltration of CML patients as the initial presentation while their bone marrow is still in the chronic phase is extremely rare. In this article, we present a case of a 51-year-old woman who was admitted to our hospital complaining about a skin nodule in her right calf and easy fatigability for 1 week...
January 19, 2021: American Journal of Dermatopathology
Alexander Augustyn, L Jeffrey Medeiros, Ethan B Ludmir, Jillian Gunther, Penny Fang, Shaoying Li, Chi Young Ok, Mikaela E Bankston, Vivek Verma, Dario Pasalic, Sairah Ahmed, Loretta J Nastoupil, Jason R Westin, Paolo Strati, Sattva S Neelapu, Ranjit Nair, Raphael E Steiner, Swaminathan P Iyer, Alma Rodriguez, Luis E Fayad, Christopher R Flowers, Bouthaina S Dabaja, Chelsea C Pinnix
We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiation therapy (RT) after a metabolic complete response to immunochemotherapy. With a median follow-up of 31.1 months (95% CI 27.4 - 34.8), 4 relapses occurred. The 3-year progression free survival (PFS), overall survival (OS), and loco-regional relapse free survival (LRFS) for the cohort were 95%, 96%, and 100%, respectively...
January 22, 2021: Leukemia & Lymphoma
Xuening Hou, Xingzhe Wang, Chen Liu, Futian Ma, Jihong Hao
No abstract text is available yet for this article.
January 20, 2021: Journal of Pediatric Hematology/oncology
Charlotte Leclercq, Fabienne Toutain, Frederic Baleydier, Arnaud G L'Huillier, Noemie Wagner, Céline Lironi, Anne-Marie Calza, Marc Ansari, Geraldine Blanchard-Rohner
Coronavirus disease-2019 in children has been linked to various clinical presentation, from paucisymptomatic cutaneous eruptions, to multisystemic inflammatory syndrome. We report the case of an 8-year-old boy who presented with persistent fever and pancytopenia, associated to a skin rash. An extensive etiological workup showed a positive serology for severe acute respiratory syndrome coronavirus 2 and Epstein-Barr virus. A few weeks later, type B acute lymphocytic leukemia was diagnosed. This case underlines the polymorphic appearance of coronavirus disease-2019 and the need for critical appraisal...
January 20, 2021: Journal of Pediatric Hematology/oncology
Zhihui Li, Xiaopei Wen, Yanping Geng, Tong Wu
INTRODUCTION: The common etiology of central nervous system (CNS) complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) includes CNS infection, metabolic abnormalities, drug toxicity, cerebrovascular events, Epstein-Barr virus-associated posttransplant lymphoproliferative diseases, and hematologic CNS relapse of leukemia. Although graft-versus-host disease (GVHD) is a major complication of allo-HSCT, its CNS involvement is exceedingly rare. CASE PRESENTATION: In this report, we describe a patient who exhibited acute myeloid leukemia with t(8;21) (q22;q22) and who suddenly lost visual acuity ~1 year after receipt of allo-HSCT...
January 20, 2021: Journal of Pediatric Hematology/oncology
Muhammad U Baig, Michael Rytting, Michael Roth, Ajaykumar C Morani, Cesar Nunez, Pei Lin, Branko Cuglievan
BACKGROUND: Overall survival of adolescents with relapsed T-cell lymphoblastic lymphoma (T-LL) remains poor with limited options for salvage therapy. The BCL-2 inhibitor venetoclax combined with hypomethylating agents like decitabine, has shown favorable responses in elderly patients with acute myeloid leukemia. OBSERVATION: We present the case of a 19-year-old adolescent with stage III relapsed and refractory T-LL who did not respond to 3 lines of salvage therapy...
January 20, 2021: Journal of Pediatric Hematology/oncology
Jamie A G Hamilton, Miyoung Y Lee, Rae Hunter, Raira S Ank, Jamie Y Story, Ganesh Talekar, Talia Sisroe, Dov B Ballak, Andrew Fedanov, Christopher C Porter, Elan Z Eisenmesser, Charles A Dinarello, Sunil S Raikar, James DeGregori, Curtis J Henry
Aging-associated declines in innate and adaptive immune responses are well documented and pose a risk for the growing aging population, which is predicted to comprise greater than 40 percent of the world's population by 2050. Efforts have been made to improve immunity in aged populations; however, safe and effective protocols to accomplish this goal have not been universally established. Aging-associated chronic inflammation is postulated to compromise immunity in aged mice and humans. Interleukin-37 (IL-37) is a potent anti-inflammatory cytokine, and we present data demonstrating that IL-37 gene expression levels in human monocytes significantly decline with age...
January 22, 2021: Aging Cell
Klervi Leuraud, David B Richardson, Elisabeth Cardis, Robert D Daniels, Michael Gillies, Richard Haylock, Monika Moissonnier, Mary K Schubauer-Berigan, Isabelle Thierry-Chef, Ausrele Kesminiene, Dominique Laurier
The Life Span Study (LSS) of Japanese atomic bomb survivors has served as the primary basis for estimates of radiation-related disease risks that inform radiation protection standards. The long-term follow-up of radiation-monitored nuclear workers provides estimates of radiation-cancer associations that complement findings from the LSS. Here, a comparison of radiation-cancer mortality risk estimates derived from the LSS and INWORKS, a large international nuclear worker study, is presented. Restrictions were made, so that the two study populations were similar with respect to ages and periods of exposure, leading to selection of 45,625 A-bomb survivors and 259,350 nuclear workers...
January 21, 2021: Radiation and Environmental Biophysics
Angela Maria Savino, Sara Isabel Fernandes, Orianne Olivares, Anna Zemlyansky, Antony Cousins, Elke K Markert, Shani Barel, Ifat Geron, Liron Frishman, Yehudit Birger, Cornelia Eckert, Sergey Tumanov, Gillian MacKay, Jurre J Kamphorst, Pawel Herzyk, Jonatan Fernández-García, Ifat Abramovich, Inbal Mor, Michela Bardini, Ersilia Barin, Sudha Janaki-Raman, Justin R Cross, Michael G Kharas, Eyal Gottlieb, Shai Izraeli, Christina Halsey
Metabolic reprogramming is a key hallmark of cancer, but less is known about metabolic plasticity of the same tumor at different sites. Here, we investigated the metabolic adaptation of leukemia in two different microenvironments, the bone marrow and the central nervous system (CNS). We identified a metabolic signature of fatty-acid synthesis in CNS leukemia, highlighting Stearoyl-CoA desaturase ( SCD1 ) as a key player. In vivo SCD1 overexpression increases CNS disease, whilst genetic or pharmacological inhibition of SCD1 decreases CNS load...
October 2020: Nature cancer
Daniel L Sun, Soumya Poddar, Roy D Pan, Ethan W Rosser, Evan R Abt, Juno Van Valkenburgh, Thuc M Le, Vincent Lok, Selena P Hernandez, Janet Song, Joanna Li, Aneta Turlik, Xiaohong Chen, Chi-An Cheng, Wei Chen, Christine E Mona, Andreea D Stuparu, Laurent Vergnes, Karen Reue, Robert Damoiseaux, Jeffrey I Zink, Johannes Czernin, Timothy R Donahue, Kendall N Houk, Michael E Jung, Caius G Radu
A potent class of isoquinoline-based α-N-heterocyclic carboxaldehyde thiosemicarbazone (HCT) compounds has been rediscovered; based upon this scaffold, three series of antiproliferative agents were synthesized through iterative rounds of methylation and fluorination modifications, with anticancer activities being potentiated by physiologically relevant levels of copper. The lead compound, HCT-13 , was highly potent against a panel of pancreatic, small cell lung carcinoma, prostate cancer, and leukemia models, with IC50 values in the low-to-mid nanomolar range...
March 1, 2020: RSC Med Chem
Stefan Terlecki-Zaniewicz, Theresa Humer, Thomas Eder, Johannes Schmoellerl, Elizabeth Heyes, Gabriele Manhart, Natalie Kuchynka, Katja Parapatics, Fabio G Liberante, André C Müller, Eleni M Tomazou, Florian Grebien
NUP98 fusion proteins cause leukemia via unknown molecular mechanisms. All NUP98 fusion proteins share an intrinsically disordered region (IDR) in the NUP98 N terminus, featuring repeats of phenylalanine-glycine (FG), and C-terminal fusion partners often function in gene control. We investigated whether mechanisms of oncogenic transformation by NUP98 fusion proteins are hardwired in their protein interactomes. Affinity purification coupled to mass spectrometry (MS) and confocal imaging of five NUP98 fusion proteins expressed in human leukemia cells revealed that shared interactors were enriched for proteins involved in biomolecular condensation and that they colocalized with NUP98 fusion proteins in nuclear puncta...
January 21, 2021: Nature Structural & Molecular Biology
Kinan Alhallak, Jennifer Sun, Katherine Wasden, Nicole Guenthner, Julie O'Neal, Barbara Muz, Justin King, Daniel Kohnen, Ravi Vij, Samuel Achilefu, John F DiPersio, Abdel Kareem Azab
T-cell-based immunotherapy, such as CAR-T cells and bispecific T-cell engagers (BiTEs), has shown promising clinical outcomes in many cancers; however, these therapies have significant limitations, such as poor pharmacokinetics and the ability to target only one antigen on the cancer cells. In multiclonal diseases, these therapies confer the development of antigen-less clones, causing tumor escape and relapse. In this study, we developed nanoparticle-based bispecific T-cell engagers (nanoBiTEs), which are liposomes decorated with anti-CD3 monoclonal antibodies (mAbs) targeting T cells, and mAbs targeting the cancer antigen...
January 21, 2021: Leukemia
Amelie Foucault, Nicolas Vallet, Noemie Ravalet, Frederic Picou, Marie C Bene, Emmanuel Gyan, Olivier Herault
The impact of pesticides on health is a major public health concern. A higher risk to develop chronic lymphoid malignancies has been demonstrated to be associated with occupational pesticide exposure (OPE). By contrast, little is known of the impact of OPE on the occurrence of myeloid malignancies especially acute myeloid leukemia (AML). The purpose of this meta-analysis is to summarize data on the association between OPE and AML. A relevant dataset of case-control studies was extracted. Among 6784 references extracted, 14 were selected, representing 3,955 AML patients and 9,948 control subjects diagnosed between 1976 and 2010...
January 21, 2021: Scientific Reports
Marco Igor Valencia-Sánchez, Pablo De Ioannes, Miao Wang, David M Truong, Rachel Lee, Jean-Paul Armache, Jef D Boeke, Karim-Jean Armache
Dot1 (disruptor of telomeric silencing-1), the histone H3 lysine 79 (H3K79) methyltransferase, is conserved throughout evolution, and its deregulation is found in human leukemias. Here, we provide evidence that acetylation of histone H4 allosterically stimulates yeast Dot1 in a manner distinct from but coordinating with histone H2B ubiquitination (H2BUb). We further demonstrate that this stimulatory effect is specific to acetylation of lysine 16 (H4K16ac), a modification central to chromatin structure. We provide a mechanism of this histone cross-talk and show that H4K16ac and H2BUb play crucial roles in H3K79 di- and trimethylation in vitro and in vivo...
January 22, 2021: Science
Sarah Brown, Charlotte Pawlyn, Avie-Lee Tillotson, Debbie Sherratt, Louise Flanagan, Eric Low, Gareth J Morgan, Cathy Williams, Martin Kaiser, Faith E Davies, Matthew W Jenner
INTRODUCTION: Outcomes continue to improve in relapsed myeloma as more effective treatment options emerge. We report a multicenter single-arm phase 2 trial evaluating toxicity and efficacy of the histone deacetylase (HDAC) inhibitor vorinostat in combination with bortezomib and dexamethasone. PATIENTS AND METHODS: Sixteen patients who had received a median of 1 prior treatment line received bortezomib subcutaneously 1.3 mg/m2 days 1, 4, 8, and 11; dexamethasone 20 mg orally days 1-2, 4-5, 8-9, and 11-12; vorinostat 400 mg orally days 1-4, 8-11, and 15-18 of a 21-day cycle...
December 3, 2020: Clinical Lymphoma, Myeloma & Leukemia
Swetha Kambhampati, Bita Fakhri, Weiyun Z Ai, Lawrence D Kaplan, Joseph M Tuscano, Matthew J Wieduwilt, Akshay Sudhindra, Erika Cavallone, Jesika Reiner, Charlie Aoun, Miguel Castillo, Michelle Martinelli, Teresa Ta, Diem Le, Michelle Padilla, Erika Crawford, Charalambos B Andreadis
INTRODUCTION: We designed a multicenter, phase Ib dose-escalation trial of carfilzomib with bendamustine and rituximab in patients with relapsed/refractory non-Hodgkin lymphoma (NCT02187133) in order to improve the response rates of this difficult-to-treat population. Chemoimmunotherapy with bendamustine and rituximab has shown activity in a variety of lymphomas, and proteasome inhibitors have demonstrated pre-clinical synergy and early clinical activity in this population. The objectives were to determine the maximum tolerated dose of carfilzomib and the preliminary efficacy of this combination...
December 24, 2020: Clinical Lymphoma, Myeloma & Leukemia
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