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https://read.qxmd.com/read/30784101/car-t-cells-for-acute-lymphoblastic-leukemia
#1
Noelle V Frey
Chimeric Antigen Receptor (CAR) modified T cells targeted to CD19 have resulted in unprecedented remission rates for adult and pediatric patients with relapsed and refractory B cell acute lymphoblastic leukemia (ALL). With regulatory approval for tisagenlecleucel and many other agents under active investigation, the use of CAR T cells for ALL continues to expand. While some remissions from anti-CD19 CAR T cells are durable without a consolidative allogeneic stem cell transplantation, CD19 positive and negative relapses remain a significant concern fueling investigations into the biology of CAR T cell persistence and the development of CARTs that target more than one antigen...
February 19, 2019: American Journal of Hematology
https://read.qxmd.com/read/30783516/characterization-and-dynamics-of-specific-t-cells-against-nucleophosmin-1-npm1-mutated-peptides-in-patients-with-npm1-mutated-acute-myeloid-leukemia
#2
Fabio Forghieri, Giovanni Riva, Ivana Lagreca, Patrizia Barozzi, Daniela Vallerini, Monica Morselli, Ambra Paolini, Paola Bresciani, Elisabetta Colaci, Monica Maccaferri, Andrea Gilioli, Vincenzo Nasillo, Andrea Messerotti, Valeria Pioli, Laura Arletti, Davide Giusti, Francesca Bettelli, Melania Celli, Francesca Donatelli, Giorgia Corradini, Sabrina Basso, Antonella Gurrado, Monica Cellini, Tommaso Trenti, Roberto Marasca, Franco Narni, Maria Paola Martelli, Brunangelo Falini, Leonardo Potenza, Mario Luppi, Patrizia Comoli
Nucleophosmin(NPM1)-mutated protein, a leukemia-specific antigen, represents an ideal target for AML immunotherapy. We investigated the dynamics of NPM1-mutated-specific T cells on PB and BM samples, collected from 31 adult NPM1 -mutated AML patients throughout the disease course, and stimulated with mixtures of 18 short and long peptides (9-18mers), deriving from the complete C-terminal of the NPM1-mutated protein. Two 9-mer peptides, namely LAVEEVSLR and AVEEVSLRK (13.9-14.9), were identified as the most immunogenic epitopes...
January 25, 2019: Oncotarget
https://read.qxmd.com/read/30782669/t-cell-activity-against-aml-improved-by-dual-targeted-t-cells-stimulated-through-t-cell-and-il7-receptors
#3
Eric Krawczyk, Sergey N Zolov, Kevin Huang, Challice L Bonifant
The development of engineered T cells to treat acute myeloid leukemia (AML) is challenging due to difficulty in target selection and the need for robust T-cell expansion and persistence. We designed a T cell stimulated to kill AML cells based on recognition of the AML-associated surface marker CLEC12A, via secretion of a CLEC12AxCD3 bispecific "engager" molecule (CLEC12A-ENG). CLEC12A-ENG T cells are specifically activated by CLEC12A, are not toxic to hematopoietic progenitor cells, and exhibit antigen-dependent AML killing...
February 19, 2019: Cancer Immunology Research
https://read.qxmd.com/read/30782173/hypericin-photodynamic-therapy-inhibits-the-growth-of-adult-t-cell-leukemia-cells-through-induction-of-apoptosis-and-suppression-of-viral-transcription
#4
Lingling Xu, Xueqing Zhang, Wenzhao Cheng, Yong Wang, Kaining Yi, Zhilong Wang, Yiling Zhang, Linxiang Shao, Tiejun Zhao
BACKGROUND: Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). ATL carries a poor prognosis due to chemotherapy resistance. Thus, it is urgent to develop new treatment strategies. Hypericin (HY) is a new-type of photosensitizer in the context of photodynamic therapy (PDT) due to its excellent photosensitizing properties and anti-tumor activities. RESULTS: In the present study, we investigated the efficacy of hypericin in ATL cells...
February 19, 2019: Retrovirology
https://read.qxmd.com/read/30779036/mrd-detection-in-b-cell-non-hodgkin-lymphomas-using-ig-gene-rearrangements-and-chromosomal-translocations-as-targets-for-real-time-quantitative-pcr
#5
Christiane Pott, Monika Brüggemann, Matthias Ritgen, Vincent H J van der Velden, Jacques J M van Dongen, Michael Kneba
Minimal residual disease (MRD) diagnostics is of high clinical relevance in patients with indolent B-cell non-Hodgkin lymphomas (B-NHL) and serves as a surrogate parameter to evaluate treatment effectiveness and long-term prognosis. MRD diagnostics performed by real-time quantitative PCR (RQ-PCR) is still the gold standard and currently the most sensitive and the most broadly applied method in follicular lymphoma (FL) and mantle cell lymphoma (MCL). Alternatively, droplet digital PCR (ddPCR) can be used for MRD monitoring in multiple myeloma, mantle cell lymphoma, and follicular lymphoma with comparable sensitivity, accuracy, and reproducibility...
2019: Methods in Molecular Biology
https://read.qxmd.com/read/30778167/human-nk-cells-surface-receptors-inhibitory-checkpoints-and-translational-applications
#6
REVIEW
Simona Sivori, Paola Vacca, Genny Del Zotto, Enrico Munari, Maria Cristina Mingari, Lorenzo Moretta
NK cells play important roles in innate defenses against viruses and in the control of tumor growth and metastasis. The regulation/induction of NK cell function is mediated by an array of activating or inhibitory surface receptors. In humans, major activating receptors involved in target cell killing are the natural cytotoxicity receptors (NCRs) and NKG2D. Activating receptors recognize ligands that are overexpressed or expressed de novo upon cell stress, viral infection, or tumor transformation. The HLA-class I-specific inhibitory receptors, including KIRs recognizing HLA-class I allotypic determinants and CD94/NKG2A recognizing the class-Ib HLA-E, constitute a fail-safe mechanism to avoid unwanted NK-mediated damage to healthy cells...
February 18, 2019: Cellular & Molecular Immunology
https://read.qxmd.com/read/30774831/association-between-tlr2-and-tlr4-expression-and-response-to-induction-therapy-in-acute-myeloid-leukemia-patients
#7
Mani Ramzi, Abolfazl Khalafi-Nezhad, Mahdiyar Iravani Saadi, Zahra Jowkar
Background: Toll-like receptors (TLRs) are a family of transmembrane pattern-recognition receptors that play a crucial role in the realization of innate and adaptive immune response. TLRs may play a role in tumor development and growth because of expression or up-regulation of functional TLRs in some tumors and tumor cell lines. The participation of TLRs in the pathogenesis of acute myeloid leukemia (AML) remains unspecified. This study aimed to investigate the effect of TLR2 and TLR4 expression in peripheral blood mononuclear cells of AML patients in response to induction chemotherapy...
October 1, 2018: International Journal of Hematology-oncology and Stem Cell Research
https://read.qxmd.com/read/30773086/evaluating-the-role-of-tregs-in-the-progression-of-multiple-myeloma
#8
Deepesh Lad, Qing Huang, Romy Hoeppli, Rosa Garcia, Lixin Xu, Megan Levings, Kevin Song, Raewyn Broady
The role of regulatory T-cells (Treg) and Th17 cells in the progression of multiple myeloma has been unclear. There are conflicting reports of the Treg and Th17 frequency being increased, decreased, and unchanged as compared with controls. In this study, we sought to characterize the T-cell subsets including Treg function in both blood and marrow compartments of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). The Treg/Th17 ratio is skewed toward the suppressive phenotype in MGUS and MM...
February 18, 2019: Leukemia & Lymphoma
https://read.qxmd.com/read/30771616/leveraging-the-medicines-for-malaria-venture-malaria-and-pathogen-boxes-to-discover-chemical-inhibitors-of-east-coast-fever
#9
James Nyagwange, Elias Awino, Edwin Tijhaar, Nicholas Svitek, Roger Pelle, Vishvanath Nene
Chemotherapy of East Coast fever, a lymphoproliferative cancer-like disease of cattle causing significant economic losses in Africa, is largely dependent on the use of buparvaquone, a drug that was developed in the late 1980's. The disease is caused by the tick-borne protozoan pathogen Theileria parva. Buparvaquone can be used prophylactically and it is also active against tropical theileriosis, caused by the related parasite Theileria annulata. Recently, drug resistance was reported in T. annulata, and could occur in T...
January 25, 2019: International Journal for Parasitology, Drugs and Drug Resistance
https://read.qxmd.com/read/30770553/8-chloro-adenosine-activity-in-flt3-itd-acute-myeloid-leukemia
#10
Ralf Buettner, Le Xuan Truong Nguyen, Bijender Kumar, Corey Morales, Chao Liu, Lisa S Chen, Tea Pemovska, Timothy W Synold, Joycelynne Palmer, Ryan Thompson, Ling Li, Dinh Hoa Hoang, Bin Zhang, Lucy Ghoda, Claudia Kowolik, Mika Kontro, Calum Leitch, Krister Wennerberg, Xiaochun Xu, Ching-Cheng Chen, David Horne, Varsha Gandhi, Vinod Pullarkat, Guido Marcucci, Steven T Rosen
Nucleoside analogs represent the backbone of several distinct chemotherapy regimens for acute myeloid leukemia (AML) and combination with tyrosine kinase inhibitors has improved survival of AML patients, including those harboring the poor-risk FLT3-ITD mutation. Although these compounds are effective in killing proliferating blasts, they lack activity against quiescent leukemia stem cells (LSCs), which contributes to initial treatment refractoriness or subsequent disease relapse. The reagent 8-chloro-adenosine (8-Cl-Ado) is a ribose-containing, RNA-directed nucleoside analog that is incorporated into newly transcribed RNA rather than in DNA, causing inhibition of RNA transcription...
February 15, 2019: Journal of Cellular Physiology
https://read.qxmd.com/read/30770347/is-there-etiologic-heterogeneity-between-subtypes-of-childhood-acute-lymphoblastic-leukemia-a-review-of-variation-in-risk-by-subtype
#11
Lindsay A Williams, Jun J Yang, Betsy A Hirsch, Erin L Marcotte, Logan G Spector
While substantial advances in the identification of cytogenomic subtypes of childhood acute lymphoblastic leukemia (ALL) have been made in recent decades, epidemiologic research characterizing the etiologic heterogeneity of ALL by subtype has not kept pace. The purpose of this review is to summarize the current literature concerning subtype-specific epidemiologic risk factor associations with ALL subtype defined by immunophenotype (e.g. B-cell vs T-cell) and cytogenomics (including gross chromosomal events characterized by recurring numerical and structural abnormalities, along with cryptic balanced rearrangements, and focal gene deletions)...
February 15, 2019: Cancer Epidemiology, Biomarkers & Prevention
https://read.qxmd.com/read/30770344/stat4-activation-by-leukemia-inhibitory-factor-confers-a-therapeutic-effect-on-intestinal-inflammation
#12
Yanan S Zhang, Dazhuan E Xin, Zhizhang Wang, Xinyang Song, Yanyun Sun, Quanli C Zou, Jichen Yue, Chenxi Zhang, Junxun M Zhang, Zhi Liu, Xiaoren Zhang, Ting C Zhao, Bing Su, Y Eugene Chin
T helper 17 (Th17)-cell differentiation triggered by interleukin-6 (IL-6) via STAT3 activation promotes inflammation in inflammatory bowel disease (IBD) patients. However, leukemia inhibitory factor (LIF), an IL-6 family cytokine, restricts inflammation by blocking Th17-cell differentiation via an unknown mechanism. Here, we report that microbiota dysregulation promotes LIF secretion by intestinal epithelial cells (IECs) in a mouse colitis model. LIF greatly activates STAT4 phosphorylation on multiple SPXX elements within the C-terminal transcription regulation domain...
February 15, 2019: EMBO Journal
https://read.qxmd.com/read/30769194/barriers-to-allogeneic-hematopoietic-stem-cell-transplant-for-human-t-cell-lymphotropic-virus-1-associated-adult-t-cell-lymphoma-leukemia-in-the-united-states-experience-from-a-large-cohort-in-a-major-tertiary-center
#13
Diego Adrianzen Herrera, Noah Kornblum, Ana Acuna-Villaorduna, R Alejandro Sica, Urvi Shah, Moya Butler, Nivetha Vishnuvardhan, Nishi Shah, Lizamarie Bachier-Rodriguez, Olga Derman, Aditi Shastri, Ioannis Mantzaris, Amit K Verma, Ira Braunchweig, Murali Janakiram
In the United States (U.S.), Adult T-Cell Lymphoma-Leukemia (ATLL) carries a dismal prognosis and mainly affects immigrants from Human T-Cell Lymphotropic Virus 1 (HTLV-1) endemic areas. Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT) can be effective and is recommended as an upfront treatment in the NCCN guidelines. We studied the barriers to alloHSCT in one of the largest ATLL populations in the U.S. Comprehensive chart and donor registry reviews were conducted for 88 ATLL patients treated at Montefiore Medical Center from 2003 to 2018...
February 12, 2019: Biology of Blood and Marrow Transplantation
https://read.qxmd.com/read/30769192/access-to-hematopoietic-stem-cell-transplantation-among-pediatric-patients-with-acute-lymphoblastic-leukemia-a-population-based-analysis
#14
Tony H Truong, Jason D Pole, Henrique Bittencourt, Tal Schechter, Geoff D E Cuvelier, Kristjan Paulson, Meera Rayar, David Mitchell, Kirk R Schultz, Debbie O'Shea, Randy Barber, Donna Wall, Lillian Sung
INTRODUCTION: Access to hematopoietic stem cell transplantation (HSCT) in pediatric acute lymphoblastic leukemia (ALL) is primarily dependent on disease-related factors but may be influenced by social and economic determinants. METHODS: We included all children < 15 years old with newly diagnosed ALL in Canada between 2001 and 2018 using the Cancer in Young People in Canada (CYP-C) national registry. We examined factors potentially associated with the likelihood of receiving HSCT using univariate and multivariable logistic regression models...
February 12, 2019: Biology of Blood and Marrow Transplantation
https://read.qxmd.com/read/30764894/high-circ_100053-predicts-a-poor-outcome-for-chronic-myeloid-leukemia-and-is-involved-in-imatinib-resistance
#15
Lei Ping, Chen Jian-Jun, Liao Chu-Shu, Liu Guang-Hua, Zhou Ming
Chronic myeloid leukemia (CML) is a rare clonal myeloproliferative malignancy, which is caused by a reciprocal translocation between chromosomes 9 and 22 t(9;22) (q34;q11). Altered circle RNAs (circRNAs) could contribute to leukemogenesis. In this study, we aimed to investigate the expression profiling of circRNAs in CML. We performed circRNA-sequencing to identify differentially expressed circRNAs in CML cells. Furthermore, we found that circ_100053 was significantly upregulated in peripheral blood mononuclear cells (PBMC) and serum samples from CML compared with healthy controls...
February 14, 2019: Oncology Research
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
#16
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/30763910/comprehensive-investigation-of-mirnome-identifies-novel-candidate-mirna-mrna-interactions-implicated-in-t-cell-acute-lymphoblastic-leukemia
#17
Małgorzata Dawidowska, Roman Jaksik, Monika Drobna, Bronisława Szarzyńska-Zawadzka, Maria Kosmalska, Łukasz Sędek, Ludomiła Machowska, Anna Lalik, Monika Lejman, Marek Ussowicz, Krzysztof Kałwak, Jerzy R Kowalczyk, Tomasz Szczepański, Michał Witt
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy originating from T-cell precursors. The genetic landscape of T-ALL has been largely characterized by next-generation sequencing. Yet, the transcriptome of miRNAs (miRNome) of T-ALL has been less extensively studied. Using small RNA sequencing, we characterized the miRNome of 34 pediatric T-ALL samples, including the expression of isomiRs and the identification of candidate novel miRNAs (not previously annotated in miRBase). For the first time, we show that immunophenotypic subtypes of T-ALL present different miRNA expression profiles...
February 11, 2019: Neoplasia: An International Journal for Oncology Research
https://read.qxmd.com/read/30763199/acute-lymphoblastic-leukemia-in-the-older-adult
#18
Ibrahim Aldoss, Stephen J Forman, Vinod Pullarkat
Acute lymphoblastic leukemia (ALL) in older adults presents a real challenge as a result of adverse disease biology and comorbidities that preclude delivering curative regimens. Conventional chemotherapy approaches have generally yielded unsatisfactory results in older patients with ALL as a result of excessive induction mortality, chemotherapy resistance of the leukemia, and the need to omit or dose reduce key drugs during the course of therapy because of adverse effects. Philadelphia chromosome-positive ALL represents about a quarter of newly diagnosed older adults, and the striking single-agent activity and excellent safety profile of tyrosine kinase inhibitors has allowed incorporation of these agents into therapy, significantly improving the outcome of older adults with Philadelphia chromosome-positive ALL...
February 2019: Journal of Oncology Practice
https://read.qxmd.com/read/30762880/current-challenges-for-car-t-cell-therapy-of-acute-myeloid-leukemia
#19
REVIEW
Tim Sauer, Cliona M Rooney
No abstract text is available yet for this article.
February 14, 2019: Transfusion
https://read.qxmd.com/read/30762706/chimeric-antigen-receptor-t-cell-toxicity
#20
DaMarcus E Baymon, Edward W Boyer
PURPOSE OF REVIEW: Chimeric antigen receptor -(CAR) T-cell therapy has become a commonly used immunotherapy originally used in the treatment of B-cell leukemias but which are now applied broadly across tumor classes. Although high rates of remission are associated with CAR T-cell therapy, toxicities associated with these novel treatment regimens can be lethal if not recognized in a timely manner. RECENT FINDINGS: Cytokine release syndrome and neurotoxicity are the two most common toxicities associated with CAR T-cell therapy...
February 11, 2019: Current Opinion in Pediatrics
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