keyword
https://read.qxmd.com/read/38516690/automated-manufacture-of-%C3%AE-npm1-tcr-engineered-t-cells-for-aml-therapy
#21
JOURNAL ARTICLE
Isabella Elias Yonezawa Ogusuku, Vera Herbel, Simon Lennartz, Caroline Brandes, Eva Argiro, Caroline Fabian, Carola Hauck, Conny Hoogstraten, Sabrina Veld, Lois Hageman, Karin Teppert, Georgia Koutsoumpli, Marieke Griffioen, Nadine Mockel-Tenbrinck, Thomas Schaser, Rosa de Groot, Ian C D Johnston, Dominik Lock
Acute myeloid leukemia (AML) is a heterogeneous malignancy that requires further therapeutic improvement, especially for the elderly and for subgroups with poor prognosis. A recently discovered T cell receptor (TCR) targeting mutant nucleophosmin 1 (ΔNPM1) presents an attractive option for the development of a cancer antigen-targeted cellular therapy. Manufacturing of TCR-modified T cells, however, is still limited by a complex, time-consuming, and laborious procedure. Therefore, this study specifically addressed the requirements for a scaled manufacture of ΔNPM1-specific T cells in an automated, closed, and good manufacturing practice-compliant process...
June 13, 2024: Molecular Therapy. Methods & Clinical Development
https://read.qxmd.com/read/38516299/car-designs-for-solid-tumors-overcoming-hurdles-and-paving-the-way-for-effective-immunotherapy
#22
JOURNAL ARTICLE
Yuanbin Cui, Mintao Luo, Chuanyuan Gu, Yuxian He, Yao Yao, Peng Li
Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized immunotherapy by modifying patients' immune cells genetically. By expressing CARs, these modified cells can specifically identify and eliminate tumor cells. The success of CAR-T therapy in hematological malignancies, such as leukemia and lymphoma, has been remarkable. Numerous studies have reported improved patient outcomes and increased survival rates. However, the application of CAR-T therapy in treating solid tumors faces significant challenges...
October 31, 2023: Biophysics Reports
https://read.qxmd.com/read/38514887/an-immunophenotype-coupled-transcriptomic-atlas-of-human-hematopoietic-progenitors
#23
JOURNAL ARTICLE
Xuan Zhang, Baobao Song, Maximillian J Carlino, Guangyuan Li, Kyle Ferchen, Mi Chen, Evrett N Thompson, Bailee N Kain, Dan Schnell, Kairavee Thakkar, Michal Kouril, Kang Jin, Stuart B Hay, Sidharth Sen, David Bernardicius, Siyuan Ma, Sierra N Bennett, Josh Croteau, Ornella Salvatori, Melvin H Lye, Austin E Gillen, Craig T Jordan, Harinder Singh, Diane S Krause, Nathan Salomonis, H Leighton Grimes
Analysis of the human hematopoietic progenitor compartment is being transformed by single-cell multimodal approaches. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) enables coupled surface protein and transcriptome profiling, thereby revealing genomic programs underlying progenitor states. To perform CITE-seq systematically on primary human bone marrow cells, we used titrations with 266 CITE-seq antibodies (antibody-derived tags) and machine learning to optimize a panel of 132 antibodies...
March 21, 2024: Nature Immunology
https://read.qxmd.com/read/38513276/laboratory-characterization-of-the-pediatric-b-t-subtype-of-mixed-phenotype-acute-leukemia-report-of-a-case-series
#24
JOURNAL ARTICLE
Irina Demina, Ekaterina Mikhailova, Elena Zerkalenkova, Alexandra Semchenkova, Julia Roumiantseva, Alexandra Borkovskaya, Evgeny Matveev, Dmitry Abramov, Dmitry Konovalov, Natalia Miakova, Natalia Ponomareva, Julia Belkina, Konstantin Kondratchik, Yulia Olshanskaya, Galina Novichkova, Alexander Karachunskiy, Alexander Popov
OBJECTIVES: Mixed-phenotype acute leukemia (MPAL) is a rare disease associated with difficulties in the correct lineage assignment of leukemic cells. One of the least common subtypes within this category is characterized by the simultaneous presence of B- and T-lineage-defining antigens. Each case of suspected B/T MPAL should be considered in light of all available laboratory and clinical data to avoid misdiagnosis. METHODS: In this study, we describe 6 pediatric patients who presented with leukemic blasts bearing B- and T-lineage antigens at diagnosis, including their clinical, immunophenotypic, morphologic, and cytogenetic characteristics...
March 21, 2024: American Journal of Clinical Pathology
https://read.qxmd.com/read/38512136/antigen-independent-autonomous-b-cell-receptor-signaling-drives-activated-b-cell-dlbcl
#25
JOURNAL ARTICLE
Janneke A Eken, Marvyn T Koning, Kristyna Kupcova, Julieta H Sepúlveda Yáñez, Ruben A L de Groen, Edwin Quinten, Jurriaan Janssen, Cornelis A M van Bergen, Joost S P Vermaat, Arjen Cleven, Marcelo A Navarrete, Bauke Ylstra, Daphne de Jong, Ondrej Havranek, Hassan Jumaa, Hendrik Veelken
Diffuse large B cell lymphoma of activated B cell type (ABC-DLBCL), a major cell-of-origin DLBCL subtype, is characterized by chronic active B cell receptor (BCR) signaling and NF-κB activation, which can be explained by activating mutations of the BCR signaling cascade in a minority of cases. We demonstrate that autonomous BCR signaling, akin to its essential pathogenetic role in chronic lymphocytic leukemia (CLL), can explain chronic active BCR signaling in ABC-DLBCL. 13 of 18 tested DLBCL-derived BCR, including 12 cases selected for expression of IgM, induced spontaneous calcium flux and increased phosphorylation of the BCR signaling cascade in murine triple knockout pre-B cells without antigenic stimulation or external BCR crosslinking...
May 6, 2024: Journal of Experimental Medicine
https://read.qxmd.com/read/38511268/steroid-free-combination-of-5-azacytidine-and-venetoclax-for-the-treatment-of-multiple-myeloma
#26
JOURNAL ARTICLE
Lyndsey Flanagan, Aisling Coughlan, Nicola Cosgrove, Andrew Roe, Yu Wang, Stephanie Gilmore, Izabela Drozdz, Claire Comerford, Jeremy Ryan, Emma Minihane, Salma Parvin, Michael O'Dwyer, John Quinn, Philip Murphy, Simon Furney, Siobhan Glavey, Tríona Ní Chonghaile
Multiple Myeloma (MM) is an incurable plasma cell malignancy, that despite an unprecedented increase in overall survival, lacks truly risk-adapted or targeted treatments. A proportion of patients with MM depend on BCL-2 for survival and recently the BCL-2 antagonist venetoclax has shown clinical efficacy and safety in t(11;14) and BCL-2 overexpressing MM. However, only a small proportion of MM patients rely on BCL-2 (~20%), there is a need to broaden the patient population outside of t(11;14) that can be treated with venetoclax...
March 21, 2024: Haematologica
https://read.qxmd.com/read/38510491/mir-539-5p-targets-bmp2-to-regulate-treg-activation-in-b-cell-acute-lymphoblastic-leukemia-through-tgf-%C3%AE-smads-mapk
#27
JOURNAL ARTICLE
Qingkai Dai, Rui Shi, Ge Zhang, Yuefang Wang, Lei Ye, Luyun Peng, Siqi Guo, Jiajing He, Hao Yang, Yongmei Jiang
MicroRNAs (mRNAs) were believed to play an important role in cancers, and this study aimed to explore the mechanism of miRNA regulating Treg in B-cell acute lymphoblastic leukemia (B-ALL). Firstly, the differentially expressed miRNAs and target genes significantly associated with Tregs were screened out by high-throughput sequencing, and their enrichment pathways were analyzed. The binding relationship between miRNA and target genes was further verified, and the effects of miRNA on the proliferation and apoptosis of B-ALL Nalm-6 cells and Treg activation were analyzed...
2024: Experimental Biology and Medicine
https://read.qxmd.com/read/38508753/-use-of-crispr-cas9-with-homology-directed-repair-hdr-to-gene-edit-topoisomerase-ii%C3%AE-in-human-leukemia-k562-cells-generation-of-a-resistance-phenotype
#28
JOURNAL ARTICLE
Jessika Carvajal-Moreno, Xinyi Wang, Victor A Hernandez, Milon Mondal, Xinyu Zhao, Jack C Yalowich, Terry S Elton
DNA topoisomerase IIβ (TOP2β/180; 180 kDa) is a nuclear enzyme that regulates DNA topology by generation of short-lived DNA double-strand breaks primarily during transcription. TOP2β/180 can be a target for DNA damage-stabilizing anticancer drugs, whose efficacy is often limited by chemoresistance. Our laboratory previously demonstrated reduced levels of TOP2β/180 (and the paralog TOP2α/170) in an acquired etoposide-resistant K562 clonal cell line, K/VP.5 in part due to overexpression of microRNA-9-3p/5p impacting post-transcriptional events...
March 20, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38507119/acute-kidney-injury-following-treatment-with-cd19-specific-car-t-cell-therapy-in-children-adolescent-and-young-adult-patients-with-b-cell-acute-lymphoblastic-leukemia
#29
JOURNAL ARTICLE
Yonique Petgrave, Subodh Selukar, Rebecca Epperly, Swati Naik, Noel DeLos Santos, Brandon M Triplett, Stephen Gottschalk, John Bissler, Aimee C Talleur
BACKGROUND: CD19-specific chimeric antigen receptor (CAR) T-cell therapy has shown promising disease responses in patients with high-risk B-cell malignancies. However, its use may be related to complications such as immune-mediated complications, infections, and end-organ dysfunction. The incidence of post-CAR T-cell therapy acute kidney injury (AKI) in the children, adolescent, and young adult (CAYA) patient population is largely unreported. METHODS: The objectives of this study were to determine the incidence of AKI in CAYA patients with high-risk B-cell malignancies treated with CD19-CAR T-cell therapy, evaluate potential risk factors for developing AKI, and determine patterns of kidney function recovery...
March 20, 2024: Pediatric Nephrology
https://read.qxmd.com/read/38506662/identification-of-enhanced-vaccine-mimotopes-for-the-p15e-murine-cancer-antigen
#30
JOURNAL ARTICLE
Shiqi Zhou, Yiting Song, Yuan Luo, Breandan Quinn, Yang Jiao, Mark D Long, Scott I Abrams, Jonathan F Lovell
Mimotopes of short CD8+ T cell epitopes generally comprise one or more mutated residues, and can increase the immunogenicity and function of peptide cancer vaccines. We recently developed a two-step approach to generate enhanced mimotopes using positional peptide microlibraries and herein applied this strategy to the broadly used H-2Kb restricted murine leukemia p15E tumor-rejection epitope. The wild-type p15E epitope (sequence: KSPWFTTL) was poorly immunogenic in mice, even when combined with a potent peptide nanoparticle vaccine system and did not delay p15E-expressing MC38 tumor growth...
March 20, 2024: Cancer Res Commun
https://read.qxmd.com/read/38506241/clinicopathological-features-of-adult-t-cell-leukemia-lymphoma-with-t-follicular-helper-phenotype
#31
JOURNAL ARTICLE
Reiji Muto, Hiroaki Miyoshi, Kazutaka Nakashima, Mai Takeuchi, Makoto Hamasaki, Koichi Ohshima
AIMS: T-follicular helper (TFH) cells are effector T-cells that are crucial for B-cell selection and differentiation. T-cell lymphomas derived from TFH cells have distinct characteristics. Additionally, in the World Health Organization (WHO) classification 5th edition, three lymphomas were introduced as independent disease entities with TFH cell origin. We aimed to investigate the clinicopathological features of adult T-cell leukemia/lymphoma (ATLL) with a TFH phenotype (TFHP). METHODS AND RESULTS: We performed TFH immunohistochemistry analysis of five biomarkers for the biopsy specimen, with TFHP being indicated by a positive result for more than two markers...
March 2024: Cancer Medicine
https://read.qxmd.com/read/38503526/-effect-of-early-tocilizumab-intervention-on-patients-with-cytokine-release-syndrome-following-chimeric-antigen-receptor-t-cell-therapy
#32
JOURNAL ARTICLE
L L Zhou, S G Ye, P Li, X C Tang, A B Liang
Objective: This study aimed to evaluate the effect of early tocilizumab intervention to relieve cytokine release syndrome (CRS) following chimeric antigen receptor T cell (CAR-T) therapy. Methods: Twenty-two patients with acute lymphoblastic leukemia who received tocilizumab to relieve CRS response after CAR-T cell infusion in our research center from October 2015 to July 2021 were retrospectively analyzed. According to the timing of tocilizumab intervention, patients were divided into the conventional and early intervention groups...
December 14, 2023: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://read.qxmd.com/read/38503519/-chinese-expert-consensus-on-diagnosis-and-treatment-of-adult-early-t-cell-precursor-acute-lymphoblastic-leukemia-2023
#33
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
December 14, 2023: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://read.qxmd.com/read/38502880/successful-treatment-of-a-fulminant-rothia-mucilaginosa-central-nervous-system-infection-in-an-adolescent-with-t-cell-acute-lymphoblastic-leukemia
#34
JOURNAL ARTICLE
Gabriela J Espinoza-Candelaria, Erica Mamauag, Andrew Bukowinski, Zachary Aldewereld
No abstract text is available yet for this article.
March 13, 2024: Pediatric Infectious Disease Journal
https://read.qxmd.com/read/38502701/vulnerability-to-apobec3g-linked-to-the-pathogenicity-of-deltaretroviruses
#35
JOURNAL ARTICLE
Takafumi Shichijo, Jun-Ichirou Yasunaga, Kei Sato, Kisato Nosaka, Kosuke Toyoda, Miho Watanabe, Wenyi Zhang, Yoshio Koyanagi, Edward L Murphy, Roberta L Bruhn, Ki-Ryang Koh, Hirofumi Akari, Terumasa Ikeda, Reuben S Harris, Patrick L Green, Masao Matsuoka
Human retroviruses are derived from simian ones through cross-species transmission. These retroviruses are associated with little pathogenicity in their natural hosts, but in humans, HIV causes AIDS, and human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia-lymphoma (ATL). We analyzed the proviral sequences of HTLV-1, HTLV-2, and simian T-cell leukemia virus type 1 (STLV-1) from Japanese macaques ( Macaca fuscata ) and found that APOBEC3G (A3G) frequently generates G-to-A mutations in the HTLV-1 provirus, whereas such mutations are rare in the HTLV-2 and STLV-1 proviruses...
March 26, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38502193/drug-regulated-cd33-targeted-car-t-cells-control-aml-using-clinically-optimized-rapamycin-dosing
#36
JOURNAL ARTICLE
Jacob Appelbaum, April E Price, Kaori Oda, Joy Zhang, Wai-Hang Leung, Giacomo Tampella, Dong Xia, Pauline Pl So, Sarah K Hilton, Claudya Evandy, Semanti Sarkar, Unja Martin, Anne-Rachel Krostag, Marissa Leonardi, Daniel E Zak, Rachael Logan, Paula Lewis, Secil Franke-Welch, Njabulo Ngwenyama, Michael Fitzgerald, Niklas Tulberg, Stephanie Rawlings-Rhea, Rebecca A Gardner, Kyle Jones, Angelica Sanabria, William Crago, John Timmer, Andrew Hollands, Brendan Eckelman, Sanela Bilic, Jim Woodworth, Adam Lamble, Philip D Gregory, Jordan Jarjour, Mark Pogson, Joshua A Gustafson, Alexander Astrakhan, Michael C Jensen
Chimeric antigen receptor (CAR) designs that incorporate pharmacologic control are desirable, however designs suitable for clinical translation are needed. We designed a fully human, rapamycin-regulated, drug product for targeting CD33+ tumors called dimerization agent regulated immunoreceptor complex (DARIC33). T cell products demonstrated target specific and rapamycin-dependent cytokine release, transcriptional responses, cytotoxicity, and in vivo antileukemic activity in the presence of as little as 1nM rapamycin...
March 19, 2024: Journal of Clinical Investigation
https://read.qxmd.com/read/38500890/priapism-as-an-unusual-symptom-of-t-cell-acute-lymphoblastic-leukemia-in-a-pediatric-case
#37
Mohammedalamin Mustafa, Ehab Hanafy, Shaima Riyad, Mustafa M Altoonisi, Waseem Aboulela
Acute lymphoblastic leukemia (ALL) in pediatric patients typically presents with recognizable symptoms such as fever, pallor, and bone pain. However, atypical manifestations can complicate the diagnostic landscape. We present a unique case of a seven-year-old male with T-cell ALL whose presenting symptom was priapism. This case underscores the need for heightened awareness among healthcare professionals regarding the diverse clinical presentations of leukemia, emphasizing the importance of a multidisciplinary team approach for comprehensive evaluation and management...
February 2024: Curēus
https://read.qxmd.com/read/38500877/metabolic-instruction-of-the-graft-versus-leukemia-immunity
#38
REVIEW
Ann-Cathrin Burk, Petya Apostolova
Allogeneic hematopoietic cell transplantation (allo-HCT) is frequently performed to cure hematological malignancies, such as acute myeloid leukemia (AML), through the graft-versus-leukemia (GVL) effect. In this immunological process, donor immune cells eliminate residual cancer cells in the patient and exert tumor control through immunosurveillance. However, GVL failure and subsequent leukemia relapse are frequent and associated with a dismal prognosis. A better understanding of the mechanisms underlying AML immune evasion is essential for developing novel therapeutic strategies to boost the GVL effect...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38499526/hematopoietic-stem-cells-with-granulo-monocytic-differentiation-state-overcome-venetoclax-sensitivity-in-patients-with-myelodysplastic-syndromes
#39
JOURNAL ARTICLE
Juan Jose Rodriguez-Sevilla, Irene Ganan-Gomez, Feiyang Ma, Kelly Chien, Monica Del Rey, Sanam Loghavi, Guillermo Montalban-Bravo, Vera Adema, Bethany Wildeman, Rashmi Kanagal-Shamanna, Alexandre Bazinet, Helen T Chifotides, Natthakan Thongon, Xavier Calvo, Jesús María Hernández-Rivas, Maria Díez-Campelo, Guillermo Garcia-Manero, Simona Colla
The molecular mechanisms of venetoclax-based therapy failure in patients with acute myeloid leukemia were recently clarified, but the mechanisms by which patients with myelodysplastic syndromes (MDS) acquire secondary resistance to venetoclax after an initial response remain to be elucidated. Here, we show an expansion of MDS hematopoietic stem cells (HSCs) with a granulo-monocytic-biased transcriptional differentiation state in MDS patients who initially responded to venetoclax but eventually relapsed. While MDS HSCs in an undifferentiated cellular state are sensitive to venetoclax treatment, differentiation towards a granulo-monocytic-biased transcriptional state, through the acquisition or expansion of clones with STAG2 or RUNX1 mutations, affects HSCs' survival dependence from BCL2-mediated anti-apoptotic pathways to TNFα-induced pro-survival NF-κB signaling and drives resistance to venetoclax-mediated cytotoxicity...
March 18, 2024: Nature Communications
https://read.qxmd.com/read/38498036/a-lineage-specific-stat5bn642h-mouse-model-to-study-nk-cell-leukemia
#40
JOURNAL ARTICLE
Klara Klein, Sebastian Kollmann, Angela Hiesinger, Julia List, Jonatan Kendler, Thorsten Klampfl, Mehak Randhawa, Jana Trifinopoulos, Barbara Maurer, Reinhard Grausenburger, Christof A Bertram, Richard H Moriggl, Thomas Rülicke, Charles G Mullighan, Agnieszka Witalisz-Siepracka, Wencke Walter, Gregor Hoermann, Veronika Sexl, Dagmar Gotthardt
Patients with T- and NK-cell neoplasms frequently have somatic STAT5B gain-of-function mutations. The most frequent STAT5B mutation is STAT5BN642H, which is known to drive murine T-cell leukemia although its role in NK-cell malignancies is unclear. Introduction of the STAT5BN642H mutation into human NK-cell lines enhances their potential to induce leukemia in mice. We have generated a mouse model that enables tissue-specific expression of STAT5BN642H and have selectively expressed the mutated STAT5B in hematopoietic cells (N642Hvav/+) or exclusively in NK cells (N642HNK/NK)...
March 18, 2024: Blood
keyword
keyword
165668
2
3
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.