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Lymphoblastic T cell lymphoma

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https://read.qxmd.com/read/30764841/clinical-trials-of-dual-target-car-t-cells-donor-derived-car-t-cells-and-universal-car-t-cells-for-acute-lymphoid-leukemia
#1
REVIEW
Juanjuan Zhao, Yongping Song, Delong Liu
The current treatment for pediatric acute lymphoblastic leukemia (ALL) is highly successful with high cure rate. However, the treatment of adult ALL remains a challenge, particularly for refractory and/or relapsed (R/R) ALL. The advent of new targeted agents, blinatumomab, inotuzumab ozogamycin, and chimeric antigen receptor (CAR) T cells, are changing the treatment paradigm for ALL. Tisagenlecleucel (kymriah, Novartis) is an autologous CD19-targeted CAR T cell product approved for treatment of R/R B cell ALL and lymphoma...
February 14, 2019: Journal of Hematology & Oncology
https://read.qxmd.com/read/30742097/downregulation-of-specific-fbxw7-isoforms-with-differential-effects-in-t-cell-lymphoblastic-lymphoma
#2
Irene Vázquez-Domínguez, Laura González-Sánchez, Pilar López-Nieva, Pablo Fernández-Navarro, María Villa-Morales, María Á Cobos-Fernández, Isabel Sastre, Mario F Fraga, Agustín F Fernández, Marcos Malumbres, María Salazar-Roa, Osvaldo Graña-Castro, Javier Santos, Pilar Llamas, José L López-Lorenzo, José Fernández-Piqueras
FBXW7 is a driver gene in T-cell lymphoblastic neoplasia acting through proteasome degradation of key proto-oncogenes. FBXW7 encodes three isoforms, α, β and γ, which differ only in the N-terminus. In this work, massive sequencing revealed significant downregulation of FBXW7 in a panel of primary T-cell lymphoblastic lymphomas characterised by the absence of mutations in its sequence. We observed that decreased expression mainly affected the FBXW7β isoform and to a lesser extent FBXW7α and may be attributed to the combined effect of epigenetic changes, alteration of upstream factors and upregulation of miRNAs...
February 11, 2019: Oncogene
https://read.qxmd.com/read/30736426/chimeric-antigen-receptor-t-cells-the-future-is-now
#3
REVIEW
Wassim Mchayleh, Prabhjot Bedi, Rajesh Sehgal, Melhem Solh
The immune system acting via cancer immune-surveillance is considered a potential target for improving outcomes among some malignancies. The ability to harness immune cells, engineer them and educate them to target cancer cells has changed the paradigm for treating non-Hodgkin's lymphomas (NHL) and acute lymphoblastic leukemia (ALL). Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable anti-tumor activity against refractory B cell malignancies. Ongoing research aims to expand the scope of this adoptive cell therapy, understanding mechanisms of resistance and reducing toxicity...
February 7, 2019: Journal of Clinical Medicine
https://read.qxmd.com/read/30735463/crispr-cas9-based-genome-editing-in-the-era-of-car-t-cell-immunotherapy
#4
January Salas-Mckee, Weimin Kong, Whitney L Gladney, Julie K Jadlowsky, Gabriela Plesa, Megan M Davis, Joseph A Fraietta
The advent of engineered T cells as a form of immunotherapy marks the beginning of a new era in medicine, providing a transformative way to combat complex diseases such as cancer. Following FDA approval of CAR T cells directed against the CD19 protein for the treatment of acute lymphoblastic leukemia and diffuse large B cell lymphoma, CAR T cells are poised to enter mainstream oncology. Despite this success, a number of patients are unable to receive this therapy due to inadequate T cell numbers or rapid disease progression...
February 8, 2019: Human Vaccines & Immunotherapeutics
https://read.qxmd.com/read/30734424/pediatric-non-hodgkin-lymphoma-characteristics-stratification-and-treatment-at-a-single-institute-in-thailand
#5
Worawut Choeyprasert, Usanarat Anurathapan, Samart Pakakasama, Nongnuch Sirachainan, Duantida Songdej, Surapong Lertthammakiat, Suradej Hongeng
BACKGROUND: In the modern era of chemotherapy, the outcome of pediatric non-Hodgkin lymphoma (NHL) continues to improve internationally. Limited data such as information on epidemiology and survival, however, are available in Asian countries. METHODS: Children (≤15 years old) diagnosed with histologically proven NHL from 1998 to 2014 were retrospectively analyzed. RESULTS: In total, 114 patients were enrolled; they were predominantly male (65...
January 2019: Pediatrics International: Official Journal of the Japan Pediatric Society
https://read.qxmd.com/read/30701029/targeting-protein-kinase-ck2-and-cdk4-6-pathways-with-a-multi-kinase-inhibitor-on108110-suppresses-pro-survival-signaling-and-growth-in-mantle-cell-lymphoma-and-t-acute-lymphoblastic-leukemia
#6
Amol Padgaonkar, Olga Rechkoblit, Rodgrigo Vasquez-Del Carpio, Venkat Pallela, Drc Venkata Subbaiah, Stephen C Cosenza, Stacey J Baker, M V Ramana Reddy, Aneel Aggarwal, E Premkumar Reddy
Overexpression and constitutive activation of CYCLIN D1 and Casein Kinase 2 are common features of many hematologic malignancies, including mantle cell lymphoma (MCL) and leukemias such as T-cell acute lymphoblastic leukemia (T-ALL). Although both CK2 and CDK4 inhibitors have shown promising results against these tumor types, none of these agents have achieved objective responses in the clinic as monotherapies. Because both proteins play key roles in these and other hematological malignancies, we have analyzed the therapeutic potential of ON108110, a novel dual specificity ATP-competitive inhibitor of protein kinase CK2 as well as CDK4/6 in MCL and T-ALL...
December 28, 2018: Oncotarget
https://read.qxmd.com/read/30691602/feline-lymphoma-and-a-high-correlation-with-feline-leukaemia-virus-infection-in-brazil
#7
T G Cristo, G Biezus, L F Noronha, L H H S Pereira, J A Withoeft, L V Furlan, L S Costa, S D Traverso, R A Casagrande
Lymphoma is the most important haemopoietic tumour in cats and has been associated with feline leukaemia virus (FeLV) infection. In Brazil, no studies have established a correlation between FeLV infection and lymphoma. The aim of this study was to characterize lymphomas arising in cats in Brazil anatomically and microscopically, and to correlate these data with FeLV infection as determined by immunohistochemistry for the FeLV gp70 antigen. Fifty-three cats with lymphoma were evaluated. The mean age of junior, prime, mature, senior and geriatric cats was 1...
January 2019: Journal of Comparative Pathology
https://read.qxmd.com/read/30686549/-car-t-cells-lymphocytes-that-express-a-chimeric-antigen-receptor
#8
C Chabannon, R Bouabdallah, S Fürst, A Granata, C Saillard, N Vey, D Mokart, E Fougereau, C Lemarie, B Mfarrej, D Blaise, B Calmels
CAR-T cells are genetically modified human lymphocytes and gene therapy medicinal products. They are developed to treat cancers that express a membrane antigen targeted by the CAR. The FDA approved the two first-in-class medicinal products in 2017 and EMA in August 2018; both are autologous CAR-T cells targeting CD19 that is expressed at the surface of normal B-cells throughout their differentiation, and on B-cell lymphoid malignancies. Clinical efficacy was demonstrated for B-cell acute lymphoblastic leukemias, non-Hodgkin's lymphoma and chronic lymphocytic leukemia, although the marketing authorizations are less liberal in terms of indications...
January 24, 2019: La Revue de Médecine Interne
https://read.qxmd.com/read/30686353/car-t-cells-indications-actuelles-en-p%C3%A3-diatrie-et-perspectives-de-d%C3%A3-veloppement
#9
Marie-Émilie Dourthe, Karima Yakouben, Delphine Chaillou, Emmanuelle Lesprit, Jean-Hugues Dalle, André Baruchel
CURRENT INDICATIONS IN CHILDREN AND PERSPECTIVES: Acute lymphoblastic leukemia (ALL) is the first cause of cancer in children. Five-year overall survival is greater than 90% but leukemia remains a major cause of death from cancer in children. A new class of immunotherapy based on a chimeric antigen receptor "CAR" targeting the CD19 on the B leukemic cells and that is transduced in an autologous or allogenic T lymphocyte will allow to transform the prognosis of refractory or relapsed B-ALL. Overall response rates range from 60 to 90% in phase I-II studies in patients with second relapse or more or with refractory disease...
December 2018: Bulletin du Cancer
https://read.qxmd.com/read/30681598/cytomegalovirus-pneumonia-in-a-patient-with-t-lymphoblastic-leukemia-lymphoma-after-allogeneic-hematopoietic-stem-cell-transplantation-a-case-report
#10
Qiuyu Li, Kai Wang, Wei Guo, Ming Lu
RATIONALE: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for hematological malignancies. Common complications are opportunistic infections and graft-versus-host disease (GVHD). Cytomegalovirus (CMV) is one of the most common causes of opportunistic infections. PATIENT CONCERNS: A 30-year-old male was diagnosed with T-cell lymphoma after persistent cough and lymphadenopathy. Fever, abdominal pain, diarrhea, rash, and dyspnea occurred after HSCT...
January 2019: Medicine (Baltimore)
https://read.qxmd.com/read/30681495/innovative-analysis-of-predictors-for-overall-survival-from-systemic-non-hodgkin-t-cell-lymphoma-using-quantile-regression-analysis
#11
Da-Yong Huang, Yi-Fei Hu, Na Wei, Li Fu, Lin Wu, Jing Shen, Jing-Shi Wang, Zhao Wang
BACKGROUND: Non-Hodgkin T/NK cell lymphoma is a rare and widely variable type of lymphoma with the most dismal prognosis. This study aimed to investigate varied impact of the clinical indicators to the overall survival (OS). METHODS: We conducted a retrospective study to identify the non-invasive clinical features of T cell lymphoma that can predict prognosis with an innovative analysis method using quantile regression. A total of 183 patients who visited a top-tier hospital in Beijing, China, were enrolled from January 2006 to December 2015...
February 5, 2019: Chinese Medical Journal
https://read.qxmd.com/read/30680780/an-introduction-to-chimeric-antigen-receptor-car-t-cell-immunotherapy-for-human-cancer
#12
REVIEW
Steven Feins, Weimin Kong, Erik F Williams, Michael C Milone, Joseph A Fraietta
Chimeric antigen receptor (CAR) T cell therapy represents a major advancement in personalized cancer treatment. In this strategy, a patient's own T cells are genetically engineered to express a synthetic receptor that binds a tumor antigen. CAR T cells are then expanded for clinical use and infused back into the patient's body to attack and destroy chemotherapy-resistant cancer. Dramatic clinical responses and high rates of complete remission have been observed in the setting of CAR T cell therapy of B cell malignancies...
January 25, 2019: American Journal of Hematology
https://read.qxmd.com/read/30680766/cutaneous-involvement-as-the-first-manifestation-of-t-lymphoblastic-lymphoma-and-review-of-the-literature
#13
Andrea Montes-Torres Andrea, Mar Llamas-Velasco, Tania M Capusan, Beatriz Aguado, Magdalena Adrados
Lymphoblastic lymphomas (LBL) are uncommon malignant neoplasms derived from immature T- or B- lymphoid progenitor cells. Although cutaneous involvement may reach 33% in B-LBL, only twelve cutaneous cases of T- LBL have been published. We report the case of a 49-year-old woman with 2-month history of erythematous-violaceous plaques in the sternal region and breasts. Histopathologic examination showed a dense monomorphus infiltrate in dermis and positive immunostainings for CD3, CD99 and terminal deoxynucleotidyl transferase, thus indicating T-LBL...
January 24, 2019: Journal of Cutaneous Pathology
https://read.qxmd.com/read/30679322/zeb2-and-lmo2-drive-immature-t-cell-lymphoblastic-leukemia-via-distinct-oncogenic-mechanisms
#14
Steven Goossens, Jueqiong Wang, Cedric Tremblay, Jelle De Medts, Sara T'Sas, Thao Nguyen, Jesslyn Saw, Katharina Haigh, David J Curtis, Pieter Van Vlierberghe, Geert Berx, Tom Taghon, Jody J Haigh
ZEB1 and ZEB2 are structurally related E-box binding homeobox transcription factors that induce epithelial to mesenchymal transitions during development and disease. As such, they regulate cancer cell invasion, dissemination and metastasis of solid tumors. In addition, their expression is associated with the gain of cancer stem cell properties and resistance to therapy. Using conditional loss-of-function mice, we have previously demonstrated that Zeb2 plays also pivotal roles in hematopoiesis, controlling important cell fate decisions, lineage commitment and fidelity...
January 24, 2019: Haematologica
https://read.qxmd.com/read/30666506/industry-s-giant-leap-into-cellular-therapy-catalyzing-chimeric-antigen-receptor-t-cell-car-t-immunotherapy
#15
REVIEW
Stacie Ittershagen, Solveig Ericson, Lamis Eldjerou, Ali Shojaee, Eric Bleickardt, Manisha Patel, Tetiana Taran, Oezlem Anak, Charlene Hall, Mimi Leung, Deborah Roccoberton, Florence Salmon, Miriam Fuchs, Vadim Romanov, David Lebwohl
PURPOSE OF REVIEW: We describe the significant technological leap from bench to bedside that was achieved through a strong academic-industry collaboration between dedicated clinicians and researchers at the University of Pennsylvania, the Children's Hospital of Philadelphia, and Novartis to commercialize the chimeric antigen receptor T cell (CAR-T) therapy tisagenlecleucel (CTL019; Kymriah®; Novartis Pharma AG, Basel, Switzerland). RECENT FINDINGS: Tisagenlecleucel was the first CAR-T therapy and the first gene therapy to receive US Food and Drug Administration approval in 2017, with an initial indication for pediatric and young adult patients with relapsed or refractory (r/r) acute lymphoblastic leukemia, followed by approval in May 2018 for a second indication in adult patients with r/r diffuse large B cell lymphoma...
January 21, 2019: Current Hematologic Malignancy Reports
https://read.qxmd.com/read/30659408/adoptive-cell-transfer-therapy-for-hepatocellular-carcinoma
#16
REVIEW
Renyu Zhang, Zhao Zhang, Zekun Liu, Ding Wei, Xiaodong Wu, Huijie Bian, Zhinan Chen
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma...
January 18, 2019: Frontiers of Medicine
https://read.qxmd.com/read/30659025/epigenetic-silencing-affects-l-asparaginase-sensitivity-and-predicts-outcome-in-t-all
#17
Aurore Touzart, Etienne Lengline, Mehdi Latiri, Mohamed Belhocine, Charlotte Smith, Xavier Thomas, Salvatore Spicuglia, Denis Puthier, Françoise Pflumio, Thibaut Leguay, Carlos Graux, Yves Chalandon, Francoise Huguet, Stéphane Leprêtre, Norbert Ifrah, Hervé Dombret, Elizabeth Macintyre, Mathilde Hunault-Berger, Nicolas Boissel, Vahid Asnafi
PURPOSE: Biological explanations for discrepancies in patients related response to chemotherapy depending on the underlying oncogenic events is a promising research area. TLX1 or TLX3 deregulated T-ALLs (TLX1/3+) share an immature cortical phenotype and similar transcriptional signatures. However, their prognostic impacts differ and inconsistent clinical outcome has been reported for TLX3. We therefore hypothesized that the overlapping transcriptional profiles of TLX1+ and TLX3+ T-ALLs would allow identification of candidate genes which might determine their distinct clinical outcomes...
January 18, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://read.qxmd.com/read/30655906/variation-of-nicotinic-subtype-%C3%AE-7-and-muscarinic-subtype-m3-acetylcholine-receptor-expression-in-three-main-types-of-leukemia
#18
Tawit Suriyo, Sadudee Chotirat, Chirayu U Auewarakul, Karnjana Chaiyot, Orathai Promsuwicha, Jutamaad Satayavivad
Cholinergic receptors, such as α7-nicotinic acetylcholine receptor (α7-nAChR) and M3-muscarinic acetylcholine receptor (M3-mAChR), have been demonstrated to serve a significant role in the proliferation, differentiation and apoptosis of leukemic cells. However, the expression of these receptors in samples from patients with leukemia remains unclear. The present study aimed to determine the expression of M3-mAChR and α7-nAChR in the bone marrow or peripheral blood of 51 patients with leukemia, including acute myeloid leukemia (AML; n=33), acute lymphoblastic leukemia (ALL; n=13), and chronic myeloid leukemia (CML; n=5)...
January 2019: Oncology Letters
https://read.qxmd.com/read/30651288/antagonism-of-iaps-enhances-car-t-cell-efficacy
#19
Jessica Michie, Paul A Beavis, Andrew J Freeman, Stephin J Vervoort, Kelly M Ramsbottom, Vignesh Narasimhan, Emily J Lelliott, Najoua Lalaoui, Robert G Ramsay, Ricky W Johnstone, John Silke, Phillip K Darcy, Ilia Voskoboinik, Conor Kearney, Jane Oliaro
Chimeric antigen receptor (CAR) T-cell therapy has proven successful in the treatment of hematological malignancies, notably acute lymphoblastic leukemia and B-cell lymphoma. However, the efficacy of CAR T cells against solid tumors is poor, likely due to tumor-associated immunosuppression. Here, we demonstrated that antagonizing the Inhibitor of Apoptosis Proteins (IAPs) with the clinical smac-mimetic, birinapant, significantly enhanced the antitumor activity of CAR T cells in a TNF-dependent manner. Enhanced tumor cell death occurred independently of the perforin-mediated granule exocytosis pathway, underscoring the cytotoxic potential of CAR T cell-derived TNF...
January 16, 2019: Cancer Immunology Research
https://read.qxmd.com/read/30629377/-recent-advances-and-future-directions-in-car-t-cell-therapy-in-pediatric-oncology
#20
Francesco Ceppi, Raffaele Renella, Manuel Diezi, Marc Ansari, Michel A Duchosal, Caroline Arber, Lana Kandalaft, George Coukos, Maja Beck-Popovic
Fighting leukemia using the immune system (antibodies, lymphocytes) is an old idea, which has already been fulfilled in allogeneic bone marrow transplantation. Indeed, the effectiveness of the transplant depends on the action of the donor lymphocytes. To limit the adverse effects on bystander organs (graft-versus-host disease), autologous T cells can be engineered to express synthetic chimeric antigen receptors (CARs) with artificially redirected antigen specificity. Autologous T cells engineered to express a CAR targeting CD19 have shown unprecedented efficacy in clinical trials for relapsed/refractory B-cell leukemias and lymphomas...
January 9, 2019: Revue Médicale Suisse
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