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T-cell acute lymphoblastic leukemia

F Yang, J Zhang, H Y Qiu, Q Wu, D Q Kong, J J Han, J Q Qi, Y Han, D P Wu
No abstract text is available yet for this article.
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Asaf D Yanir, Caridad A Martinez, Ghadir Sasa, Kathryn Leung, Stephen Gottschalk, Bilal Omer, Nabil Ahmed, Meenakshi Hegde, Jo Eunji, Hao Liu, Helen E Heslop, Malcolm K Brenner, Robert A Krance, Swati Naik
Hematopoietic stem cell transplantation (HSCT) is the only curative option for a subset of patients with high-risk or relapsed Acute Lymphoblastic Leukemia (ALL). Given evolving practices, it is important to continually evaluate outcomes for pediatric ALL following HSCT. Outcomes after HSCT are influenced by the type of donor used as this determines the degree and method of T-cell depletion used, and consequently, specific transplant-related morbidities. We retrospectively analyzed HSCT data from our center for transplants performed between January 2008 and May 2016, comparing outcomes between different donor types...
March 14, 2018: Biology of Blood and Marrow Transplantation
Hamid Reza Mirzaei, Hossein Pourghadamyari, Majid Rahmati, Abbas Mohammadi, Javid Sadri Nahand, Abbas Rezaei, Hamed Mirzaei, Jamshid Hadjati
Recently clinical trials utilizing genetically engineered T cells expressing a chimeric antigen receptor (CAR) that is half monoclonal antibody and half T-cell receptor have demonstrated remarkable response in patients with advanced cancers like relapsed or refractory acute lymphoblastic leukemia (ALL) and lymphoma. Moreover, emerging chimeric genome editing tools such as zinc-finger nucleases (ZNFs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas composed of sequence-specific DNA binding module(s) linked to a non-specific DNA cleavage domain have made possible to dramatically expand the ability to manipulate cells aim to treat and/or study a wide range of diseases including cancer...
March 12, 2018: Cancer Letters
Li-Na Zhang, Yongping Song, Delong Liu
The prognosis of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains dismal even at this day and age. With salvage chemotherapy, only 29% (range 18 to 44%) of the patients with R/R ALL can be induced into complete remission (CR), with a median overall survival (OS) of 4 months (range 2-6 months). Blinatumomab and inotuzumab ozogamycin (IO) are immunotherapeutic agents that increased CR to 80% and extended survival to 7.7 months in this high-risk population of patients. In the last few years, chimeric antigen receptor (CAR)--engineered T cells have led to major progress in cancer immunotherapy...
March 15, 2018: Journal of Hematology & Oncology
Natthakan Thongon, Chiara Zucal, Vito Giuseppe D'Agostino, Toma Tebaldi, Silvia Ravera, Federica Zamporlini, Francesco Piacente, Ruxanda Moschoi, Nadia Raffaelli, Alessandro Quattrone, Alessio Nencioni, Jean-Francois Peyron, Alessandro Provenzani
Background: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance. Methods: We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, and by exploiting an integrated approach based on genetic, biochemical, and genome wide analyses, we annotated the drug resistance mechanisms...
2018: Cancer & Metabolism
Sarah D Cramer, Julie A Hixon, Caroline Andrews, Ross J Porter, Gisele O L Rodrigues, Xiaolin Wu, Tim Back, Kelli Czarra, Helen Michael, Maggie Cam, Jack Chen, Dominic Esposito, Emilee Senkevitch, Vijay Negi, Peter D Aplan, Wenqing Li, Scott K Durum
No abstract text is available yet for this article.
February 15, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Diana Bellavia, Rocco Palermo, Maria Pia Felli, Isabella Screpanti, Saula Checquolo
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Although the therapy of ALL has significantly improved, the heterogeneous genetic landscape of the disease often causes relapse, which is difficult to treat. Achieving a positive outcome for patients with relapsed or refractory ALL remains a challenging issue. The high prevalence of NOTCH-activating mutations in T-cell acute lymphoblastic leukemia (T-ALL) and the central role of NOTCH signaling in regulating cell survival and growth of ALL provide a rationale for the development of Notch signaling-targeted strategies in this disease...
March 12, 2018: Expert Opinion on Therapeutic Targets
Jeannine S McCune
Immunotherapy is now the fourth pillar of cancer therapy, with surgery, radiation, and traditional chemotherapy being the remaining pillars. Over the past decade, enthusiasm for immunotherapy has increased because of, in part, data showing that it consistently improves overall survival in select patients with historically refractory cancers. This issue covers various aspects of immunotherapy ranging from use of 1) chimeric antigen receptor (CAR) T cells to treat patients with B-cell acute lymphoblastic leukemia; 2) population pharmacokinetic/dynamic modeling to develop new immune checkpoint inhibitors; and 3) simulations of existing population pharmacokinetic models of immunotherapy to minimize waste without compromising exposure and efficacy...
April 2018: Clinical Pharmacology and Therapeutics
Meghdad Abdollahpour-Alitappeh, Seyed Masoud Hashemi Karouei, Majid Lotfinia, Amir Amanzadeh, Mahdi Habibi-Anbouhi
Rituximab is a chimeric monoclonal antibody directed against B-lymphocyte specific antigen CD20, which is used for the treatment of B-cell malignancies. However, the effectiveness of rituximab is limited partly due to treatment resistance. The aim of this study was to develop rituximab-based antibody drug conjugate (ADC) to enhance rituximab activity. In this study, monomethyl auristatin E (MMAE) was covalently conjugated to dithiothreitol -reduced rituximab via a valine-citrulline peptide linker (rituximab-vcMMAE)...
March 9, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Nadine Farah, Amy A Kirkwood, Sunniyat Rahman, Theresa Leon, Sarah Jenkinson, Rosemary E Gale, Katharine Patrick, Jeremy Hancock, Sujith Samarasinghe, David C Linch, Anthony V Moorman, Nicholas Goulden, Ajay Vora, Marc R Mansour
No abstract text is available yet for this article.
March 8, 2018: Haematologica
Magnus Borssén, Jessica Nordlund, Zahra Haider, Mattias Landfors, Pär Larsson, Jukka Kanerva, Kjeld Schmiegelow, Trond Flaegstad, Ólafur Gísli Jónsson, Britt-Marie Frost, Josefine Palle, Erik Forestier, Mats Heyman, Magnus Hultdin, Gudmar Lönnerholm, Sofie Degerman
Background: Few biological markers are associated with survival after relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In pediatric T-cell ALL, we have identified promoter-associated methylation alterations that correlate with prognosis. Here, the prognostic relevance of CpG island methylation phenotype (CIMP) classification was investigated in pediatric BCP-ALL patients. Methods: Six hundred and one BCP-ALL samples from Nordic pediatric patients (age 1-18) were CIMP classified at initial diagnosis and analyzed in relation to clinical data...
2018: Clinical Epigenetics
Ciprian Tomuleasa, Shigeo Fuji, Cristian Berce, Anca Onaciu, Sergiu Chira, Bobe Petrushev, Wilhelm-Thomas Micu, Vlad Moisoiu, Ciprian Osan, Catalin Constantinescu, Sergiu Pasca, Ancuta Jurj, Laura Pop, Ioana Berindan-Neagoe, Delia Dima, Shigehisa Kitano
Chimeric antigen receptor (CAR) T-cell technology has seen a rapid development over the last decade mostly due to the potential that these cells may have in treating malignant diseases. It is a generally accepted principle that very few therapeutic compounds deliver a clinical response without treatment-related toxicity, and studies have shown that CAR T-cells are not an exception to this rule. While large multinational drug companies are currently investigating the potential role of CAR T-cells in hematological oncology, the potential of such cellular therapies are being recognized worldwide as they are expected to expand in the patient to support the establishment of the immune memory, provide a continuous surveillance to prevent and/or treat a relapse, and keep the targeted malignant cell subpopulation in check...
2018: Frontiers in Immunology
Roberta Bortolozzi, Silvia Bresolin, Elena Rampazzo, Maddalena Paganin, Francesca Maule, Elena Mariotto, Daniele Boso, Sonia Minuzzo, Valentina Agnusdei, Giampietro Viola, Geertruy Te Kronnie, Giovanni Cazzaniga, Giuseppe Basso, Luca Persano
BACKGROUND: Despite chemotherapy intensification, a subgroup of high-risk paediatric T-cell acute lymphoblastic leukemia (T-ALL) patients still experience treatment failure. In this context, we hypothesised that therapy resistance in T-ALL might involve aldo-keto reductase 1C (AKR1C) enzymes as previously reported for solid tumors. METHODS: Expression of NRF2-AKR1C signaling components has been analysed in paediatric T-ALL samples endowed with different treatment outcomes as well as in patient-derived xenografts of T-ALL...
March 8, 2018: British Journal of Cancer
Amir Behdad, Pamela Allen, Xinyan Lu, Xiaolong Alan Zhou, Joan Guitart, Qing Chen, Barbara Pro
Patients with PDGFRA-rearranged hematopoietic neoplasms typically present with chronic eosinophilic leukemia and rarely with acute myeloid leukemia or T-lymphoblastic lymphoma. However, mature T-cell lymphoma has not been previously associated with PDGFRA aberrations. We report a patient who presented with simultaneous T-lymphoblastic lymphoma, focal myeloid proliferation, and cutaneous cytotoxic T-cell lymphoma refractory to chemotherapy. The presence of myeloid and lymphoid lineages prompted genetic and molecular studies...
February 21, 2018: American Journal of Dermatopathology
Ping-Pin Zheng, Johan M Kros, Jin Li
Two autologous chimeric antigen receptor (CAR) T cell therapies (Kymriah™ and Yescarta™) were recently approved by the FDA. Kymriah™ for the treatment of pediatric patients and young adults with refractory or relapse (R/R) B cell precursor acute lymphoblastic leukemia and Yescarta™ for the treatment of adult patients with R/R large B cell lymphoma. In common, both drugs are CD19-specific CAR T cell therapies lysing CD19-positive targets. Their dramatic efficacy in the short term has been highlighted by many media reports...
March 1, 2018: Drug Discovery Today
David Porter, Noelle Frey, Patricia A Wood, Yanqiu Weng, Stephan A Grupp
BACKGROUND: Anti-CD19 CAR T cell therapy has demonstrated high response rates in patients with relapsed or refractory (r/r) B cell malignancies but is associated with significant toxicity. Cytokine release syndrome (CRS) is the most significant complication associated with CAR T cell therapy, and it is critical to have a reproducible and easy method to grade CRS after CAR T cell infusions. DISCUSSION: The Common Terminology Criteria for Adverse Events scale is inadequate for grading CRS associated with cellular therapy...
March 2, 2018: Journal of Hematology & Oncology
Eigil Kjeldsen, Christine J F Nielsen, Amit Roy, Cinzia Tesauro, Ann-Katrine Jakobsen, Magnus Stougaard, Birgitta R Knudsen
Acquisition of resistance to topoisomerase I (TOP1)-targeting camptothecin (CPT) derivatives is a major clinical problem. Little is known about the underlying chromosomal and genomic mechanisms. We characterized the CPT-K5 cell line expressing mutant CPT-resistant TOP1 and its parental T-cell derived acute lymphoblastic leukemia CPT-sensitive RPMI-8402 cell line by karyotyping and molecular genetic methods, including subtractive oligo-based array comparative genomic hybridization (soaCGH) analysis. Karyotyping revealed that CPT-K5 cells had acquired additional structural aberrations and a reduced modal chromosomal number compared to RPMI-8402...
March 2018: Cancer Genomics & Proteomics
Charles E de Bock, Sofie Demeyer, Sandrine Degryse, Delphine Verbeke, Bram Sweron, Olga Gielen, Roel Vandepoel, Carmen Vicente, Marlies Vanden Bempt, Antonis Dagklis, Ellen Geerdens, Simon Bornschein, Rik Gijsbers, Jean Soulier, Jules P Meijerink, Merja Heinäniemi, Susanna Teppo, Maria Bouvy-Liivrand, Olli Lohi, Enrico Radaelli, Jan Cools
Leukemia is caused by the accumulation of multiple genomic lesions in hematopoietic precursor cells. However, how these events cooperate during oncogenic transformation remains poorly understood. We studied the cooperation between activated JAK3/STAT5 signaling and HOXA9 overexpression, two events identified as significantly co-occurring in T-cell acute lymphoblastic leukemia. Expression of mutant JAK3 and HOXA9 led to a rapid development of leukemia originating from multipotent or lymphoid-committed progenitors, with a significant decrease in disease latency compared to JAK3 or HOXA9 alone...
March 1, 2018: Cancer Discovery
Manman Deng, Jie Zha, Zhiwu Jiang, Xian Jia, Yuanfei Shi, Peng Li, Xiao Lei Chen, Zhihong Fang, Zhiqiang Du, Bing Xu
BACKGROUND: Acute lymphoblastic leukemia (ALL) is a clonal malignant disorder characterized by an uncontrolled proliferation of immature B or T lymphocytes. Extensive studies have suggested an involvement of angiogenesis signaling in ALL progression and resistance to treatment. Thus, targeting angiogenesis with anti-angiogenic drugs may be a promising approach for ALL treatment. In this study, we investigated the effectiveness of Apatinib, a novel receptor tyrosine kinase inhibitor selectively targeting VEGFR-2 in ALL cells...
February 28, 2018: Journal of Translational Medicine
Alexey Teplyakov, Galina Obmolova, Jinquan Luo, Gary L Gilliland
CD19 is a transmembrane protein expressed on malignant B cells, but not in other lineages or other tissues, which makes it an attractive target for monoclonal antibody-mediated immunotherapy. Anti-CD19 antibody B43 was utilized in a bispecific T-cell engager (BiTE) blinatumomab, that demonstrated potency for the treatment of relapsed acute lymphoblastic leukemia. To gain insight into the mechanism of action of the antibody, the crystal structure of B43 Fab was determined in complex with CD19 and in the unbound form...
February 28, 2018: Proteins
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