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T-cell acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/28533941/changes-in-clinical-laboratory-parameters-and-pharmacodynamic-markers-in-response-to-blinatumomab-treatment-of-patients-with-relapsed-refractory-all
#1
Virginie Nägele, Andrea Kratzer, Gerhard Zugmaier, Chris Holland, Youssef Hijazi, Max S Topp, Nicola Gökbuget, Patrick A Baeuerle, Peter Kufer, Andreas Wolf, Matthias Klinger
BACKGROUND: Blinatumomab has shown a remission rate of 69% in an exploratory single-arm, phase II dose-escalation study in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We evaluated changes in laboratory parameters and immunopharmacodynamic markers in patients who received blinatumomab in the exploratory phase II study. METHODS: Data from 36 adults with relapsed/refractory ALL receiving blinatumomab as 4-week continuous IV infusions in various dose cohorts were analyzed for changes in liver enzymes, first-dose parameters, peripheral blood cell subpopulations, and cytokine/granzyme B release...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28532177/targeting-non-hodgkin-lymphoma-with-blinatumomab
#2
Sheilagh Sanders, Douglas A Stewart
Management of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) remains challenging, and novel effective agents are eagerly awaited. Blinatumomab is a bispecific T-cell engager, targeting CD19. While blinatumomab's primary clinical use has been in B-cell acute lymphoblastic leukemia (B-ALL), there are increasing data for its use in B-lineage lymphomas. Areas covered: The aim of this review is to highlight the clinical data for blinatumomab use in NHL. Herein, the authors provide an overview of blinatumomab, its mechanism of action, its proven efficacy against B-ALL, and its phase I-II data assessing its use in NHL Expert opinion: Blinatumomab has modest activity in phase I-II trials in NHL, and may represent a means of bridging patients with relapsed disease to hematopoietic stem cell transplant...
May 22, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28526832/identification-of-a-novel-chalcone-derivative-that-inhibits-notch-signaling-in-t-cell-acute-lymphoblastic-leukemia
#3
Mattia Mori, Luca Tottone, Deborah Quaglio, Nadezda Zhdanovskaya, Cinzia Ingallina, Marisa Fusto, Francesca Ghirga, Giovanna Peruzzi, Maria Elisa Crestoni, Fabrizio Simeoni, Francesca Giulimondi, Claudio Talora, Bruno Botta, Isabella Screpanti, Rocco Palermo
Notch signaling is considered a rational target in the therapy of several cancers, particularly those harbouring Notch gain of function mutations, including T-cell acute lymphoblastic leukemia (T-ALL). Although currently available Notch-blocking agents are showing anti-tumor activity in preclinical studies, they are not effective in all the patients and often cause severe side-effects, limiting their widespread therapeutic use. Here, by functional and biological analysis of the most representative molecules of an in house library of natural products, we have designed and synthetized the chalcone-derivative 8 possessing Notch inhibitory activity at low micro molar concentration in T-ALL cell lines...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28518092/isolation-of-the-side-population-in-myc-induced-t-cell-acute-lymphoblastic-leukemia-in-zebrafish
#4
Margaret M Pruitt, Wilfredo Marin, Michael R Waarts, Jill L O de Jong
Heterogeneous cell populations, from either healthy or malignant tissues, may contain a population of cells characterized by a differential ability to efflux the DNA-binding dye Hoechst 33342. This "side population" of cells can be identified using flow cytometric methods after the Hoechst 33342 dye is excited by an ultraviolet (UV) laser. The side population of many cell types contains stem- or progenitor-like cells. However, not all cell types have an identifiable side population. Danio rerio, zebrafish, have a robust in vivo model of T-cell acute lymphoblastic leukemia (T-ALL), but whether these zebrafish T-ALLs have a side population is unknown...
May 4, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28510690/trichosporonosis-in-pediatric-patients-with-a-hematologic-disorder
#5
Catherine E Foster, Morven S Edwards, Julienne Brackett, Deborah A Schady, C Mary Healy, Carol J Baker
Background.: Trichosporonosis is an emerging and often fatal opportunistic fungal infection in immunocompromised patients, particularly those with hematologic malignancy, but data in children are lacking. Methods.: We report here 3 cases of invasive infection caused by Trichosporon asahii in pediatric patients with acute lymphoblastic leukemia at Texas Children's Hospital in Houston, Texas. We also conducted a literature review and identified 16 additional reports of pediatric patients with invasive T asahii infection and an underlying malignant or nonmalignant hematologic disorder...
May 16, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28508352/pediatric-precursor-b-acute-lymphoblastic-leukemia-are-t-helper-cells-the-missing-link-in-the-infectious-etiology-theory
#6
REVIEW
Simone Bürgler, David Nadal
Precursor B acute lymphoblastic leukemia (BCP-ALL), the most common childhood malignancy, arises from an expansion of malignant B cell precursors in the bone marrow. Epidemiological studies suggest that infections or immune responses to infections may promote such an expansion and thus BCP-ALL development. Nevertheless, a specific pathogen responsible for this process has not been identified. BCP-ALL cells critically depend on interactions with the bone marrow microenvironment. The bone marrow is also home to memory T helper (Th) cells that have previously expanded during an immune response in the periphery...
December 2017: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/28500740/children-with-low-risk-acute-lymphoblastic-leukemia-are-at-highest-risk-of-second-cancers
#7
Stine N Nielsen, Frank Eriksson, Susanne Rosthoej, Mette K Andersen, Erik Forestier, Henrik Hasle, Lisa L Hjalgrim, Ann Aasberg, Jonas Abrahamsson, Mats Heyman, Ólafur G Jónsson, Kaie Pruunsild, Goda E Vaitkeviciené, Kim Vettenranta, Kjeld Schmiegelow
BACKGROUND: The improved survival rates for childhood acute lymphoblastic leukemia (ALL) may be jeopardized by the development of a second cancer, which has been associated with thiopurine therapy. PROCEDURE: We retrospectively analyzed three sequential Nordic Society of Paediatric Haematology and Oncology's protocols characterized by increasing intensity of thiopurine-based maintenance therapy. We explored the risk of second cancer in relation to protocols, risk group, thiopurine methyltransferase (TPMT) activity, ALL high hyperdiploidy (HeH), and t(12;21)[ETV6/RUNX1]...
May 13, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28497658/toxic-epidermal-necrolysis-in-a-child-6-months-post-hematopoietic-stem-cell-transplantation
#8
Utako Oba, Hiroshi Yamada, So-Ichi Suenobu, Yusuke Nakamura, Akiko Ito, Yutaka Hatano, Nobuyoshi Itonaga, Kouichi Ohshima, Yuhki Koga, Shouichi Ohga, Kenji Ihara
TEN is a rare and critical disease mostly caused by drugs. It is mediated by activated CD8+ T cells that cause keratinocyte apoptosis with the assistance of cytokines/chemokines. We herein report a pediatric case of TEN after allogeneic HSCT with precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) in second complete remission. Although we did not evaluate the T-cell subpopulation in blood or skin lesion of the patient, an imbalanced immune reconstitution after HSCT might additively contribute to the development of TEN...
May 12, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28495792/cd70-reverse-signaling-enhances-nk-cell-function-and-immunosurveillance-in-cd27-expressing-b-cell-malignancies
#9
Mohamad F Al Sayed, Carla A Ruckstuhl, Tamara Hilmenyuk, Christina Claus, Jean-Pierre Bourquin, Beat C Bornhauser, Ramin Radpour, Carsten Riether, Adrian F Ochsenbein
The interaction of the tumor necrosis factor receptor (TNFR) CD27 with its ligand CD70 is an emerging target to treat cancer. CD27 signaling provides costimulatory signals to cytotoxic T cells but also increases the frequency of regulatory T cells (Tregs). Similar to other TNFR-ligands, CD70 has been shown to initiate intracellular signaling pathways (CD70 reverse signaling). CD27 is expressed on a majority of B cell non-Hodgkin lymphoma (NHL), but its role in the immune control of lymphoma and leukemia is unknown...
May 11, 2017: Blood
https://www.readbyqxmd.com/read/28494052/association-of-minimal-residual-disease-with-clinical-outcome-in-pediatric-and-adult-acute-lymphoblastic-leukemia-a-meta-analysis
#10
Donald A Berry, Shouhao Zhou, Howard Higley, Lata Mukundan, Shuangshuang Fu, Gregory H Reaman, Brent L Wood, Gary J Kelloff, J Milburn Jessup, Jerald P Radich
Importance: Minimal residual disease (MRD) refers to the presence of disease in cases deemed to be in complete remission by conventional pathologic analysis. Assessing the association of MRD status following induction therapy in patients with acute lymphoblastic leukemia (ALL) with relapse and mortality may improve the efficiency of clinical trials and accelerate drug development. Objective: To quantify the relationships between event-free survival (EFS) and overall survival (OS) with MRD status in pediatric and adult ALL using publications of clinical trials and other databases...
May 11, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28490811/high-efficacy-and-safety-of-low-dose-cd19-directed-car-t-cell-therapy-in-51-refractory-or-relapsed-b-acute-lymphoblastic-leukemia-patients
#11
J Pan, J Yang, B Deng, X Zhao, X Zhang, Y Lin, Y Wu, Z Deng, Y Zhang, S Liu, T Wu, P Lu, D Lu, A H Chang, C Tong
Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD(+)) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T cell infusion dosages were initially ranged from 0.05 to 14 × 10(5)/kg and were eventually settled at 1 × 10(5)/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD(+) patients achieved MRD(-)...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28487980/combination-of-bortezomib-and-daunorubicin-in-the-induction-of-apoptosis-in-t-cell-acute-lymphoblastic-leukemia
#12
Xin Du, Jia Tong, Hongying Lu, Cong He, Shenghong Du, Peimin Jia, Weili Zhao, Hanzhang Xu, Junmin Li, Zhixiang Shen, Yingli Wu, Jianhua Tong, Li Zhou
Despite advances in the treatment of T‑cell acute lymphoblastic leukemia (T‑ALL), the outcome of T‑ALL treatment remains unsatisfactory, therefore, more effective treatment is urgently required. The present study examined the cytotoxicities of bortezomib in combination with daunorubicin against human Jurkat and Molt‑4 T‑ALL cells and primary T‑ALL cells. Compared with treatment alone, co‑exposure of cells to bortezomib and daunorubicin resulted in a significant increase in cell death in the Jurkat cells, as evidenced by the increased percentage of Annexin V‑positive cells, the formation of apoptotic bodies...
May 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28484265/jak-stat-pathway-inhibition-overcomes-il7-induced-glucocorticoid-resistance-in-a-subset-of-human-t-cell-acute-lymphoblastic-leukemias
#13
C Delgado-Martin, L K Meyer, B J Huang, K A Shimano, M S Zinter, J V Nguyen, G A Smith, J Taunton, S S Winter, J R Roderick, M A Kelliher, T M Horton, B L Wood, D Teachey, M L Hermiston
While outcomes for children with T-cell acute lymphoblastic leukemia (T-ALL) have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid (GC) resistance is more common than resistance to other chemotherapies at relapse. Additionally, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor (ETP) T-ALLs as well as in a subset of non-ETP T-ALLs...
May 9, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28482719/mef2c-dysregulated-pediatric-t-cell-acute-lymphoblastic-leukemia-is-associated-with-cdkn1b-deletions-and-a-poor-response-to-glucocorticoid-therapy
#14
Sara Colomer-Lahiguera, Markus Pisecker, Margit König, Karin Nebral, Winfried F Pickl, Maximilian O Kauer, Oskar A Haas, Reinhard Ullmann, Andishe Attarbaschi, Michael N Dworzak, Sabine Strehl
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease in which multiple genetic abnormalities cooperate in the malignant transformation of T-lymphoid progenitors. Although in pediatric T-ALL, CDKN1B deletions occur in about 12% of the cases and represent one of the most frequent copy number alterations, neither their association with other genetic alterations nor the clinical characteristics of these patients have been determined yet. In this study, we show that loss of CDKN1B increased the prevalence of cell cycle regulator defects in immature T-ALL, usually only ascribed to CDKN2A/B deletions, and that CDKN1B deletions frequently coincide with expression of MEF2C, considered as one of the driving oncogenes in immature early T-cell precursor (ETP) ALL...
May 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28481732/human-cap10-like-protein-46%C3%A2-kda-gene-promotes-malignancy-in-colorectal-cancer
#15
Honghong Fang, Qiaoyun Chu, Jie Zhang, Hao Wang, Xinwei Yu, Siqi Ge, Manshu Song, Lijuan Wu, Minglin Lang, Naibai Chang, Youxin Wang, Wei Wang
Colon cancer patients have major unmet needs in terms of robust diagnostics and molecular biomarkers for personalized therapeutics. We have previously reported that human CAP10-like protein 46 kDa (hCLP46) is overexpressed in human acute myelogenous leukemia, T acute lymphoblastic leukemia, and leukemia cell lines. We extend this line of biomarker and diagnostic discovery research by investigating hCLP46 expression in colorectal cancer (CRC) tissues and examine the possibility of hCLP46 as a candidate biomarker for diagnosis and prognosis of CRC...
May 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28479419/novel-tumor-suppressor-function-of-klf4-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#16
REVIEW
Ye Shen, Taylor J Chen, H Daniel Lacorazza
Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy in pediatric patients. Despite advances in the treatment of this disease, many children with T-cell ALL (T-ALL) die from disease relapse due to low responses to standard chemotherapy and the lack of a targeted therapy that selectively eradicates the chemoresistant leukemia-initiating cells (LICs) responsible for disease recurrence. We recently reported that the reprogramming factor KLF4 has tumor-suppressive function in children with T-ALL...
May 4, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28477199/b16-lung-melanoma-model-to-study-the-role-of-th9-cells-in-cancer
#17
Alka Dwivedi, Sushant Kumar, Rahul Purwar
T cell therapy has shown remarkable promise in multiple malignancies including melanoma and Acute Lymphoblastic Leukemia (ALL). Recent data demonstrated the differential efficacy of various subsets of T-helper cells in tumor regression. Th9 cells, the new member of T helper cell family, possess superior anti-tumor activity compared to Th1 and Th2 cells in murine model of melanoma. Therefore, it is important to examine the anti-tumor activity of specific subsets of Th cells in tumor models. Here, we describe the methodology of examining the anti-tumor activity of Th9 cells in murine model of melanoma...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28476187/early-age-acute-leukemia-revisiting-two-decades-of-the-brazilian-collaborative-study-group
#18
REVIEW
Maria S Pombo-de-Oliveira, Francianne Gomes Andrade
The understanding of leukemogenesis in early-age acute leukemia (EAL) has improved remarkably. Initiating somatic mutations detected in dried neonatal blood spots (DNBS) and in cord blood samples of affected children with leukemia have been proven to be acquired prenatally. However, to date, few epidemiological studies have been carried out exploring EAL that include infants and children 13-24 months of age at the diagnosis. Maternal exposure to transplacental DNA-damaging substances during pregnancy has been suggested to be a risk factor for EAL...
November 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/28469959/treatment-with-the-c-c-chemokine-receptor-type-5-ccr5-inhibitor-maraviroc-suppresses-growth-and-induces-apoptosis-of-acute-lymphoblastic-leukemia-cells
#19
Jie Zi, Shushu Yuan, Jianlin Qiao, Kai Zhao, Linyan Xu, Kunming Qi, Kailin Xu, Lingyu Zeng
Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy diagnosed in children and is a malignant disorder that originates from one single hematopoietic precursor committed to B- or T-cell lineage. C-C chemokine receptor type 5 (CCR5) is a chemokine and chemokine receptor pair playing critical roles in tumorigenesis. A highly potent competitive antagonist of CCR5, maraviroc, recently has been identified with suppression of cancer cells aggressive in a variety of cancers. However, the effects of maraviroc on ALL cells have not yet been defined...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28466386/current-status-and-perspectives-of-chimeric-antigen-receptor-modified-t-cells-for-cancer-treatment
#20
REVIEW
Zhenguang Wang, Yelei Guo, Weidong Han
Chimeric antigen receptor (CAR) is a recombinant immunoreceptor combining an antibody-derived targeting fragment with signaling domains capable of activating cells, which endows T cells with the ability to recognize tumor-associated surface antigens independent of the expression of major histocompatibility complex (MHC) molecules. Recent early-phase clinical trials of CAR-modified T (CAR-T) cells for relapsed or refractory B cell malignancies have demonstrated promising results (that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia (B-ALL))...
May 2, 2017: Protein & Cell
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