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T-cell acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/28074072/targeting-bet-proteins-improves-the-therapeutic-efficacy-of-bcl-2-inhibition-in-t-cell-acute-lymphoblastic-leukemia
#1
S Peirs, V Frismantas, F Matthijssens, W Van Loocke, T Pieters, N Vandamme, B Lintermans, M P Dobay, G Berx, B Poppe, S Goossens, B C Bornhauser, J-P Bourquin, P Van Vlierberghe
Inhibition of anti-apoptotic BCL-2 has recently emerged as a promising new therapeutic strategy for the treatment of a variety of human cancers, including leukemia. Here, we used T-cell acute lymphoblastic leukemia as a model system to identify novel synergistic drug combinations with the BH3 mimetic venetoclax (ABT-199). In vitro drug screening in primary leukemia specimens that were derived from patients with high risk of relapse or relapse and cell lines revealed synergistic activity between venetoclax and the BET bromodomain inhibitor JQ1...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074066/preclinical-targeting-of-aggressive-t-cell-malignancies-using-anti-cd5-chimeric-antigen-receptor
#2
K H Chen, M Wada, K G Pinz, H Liu, K-W Lin, A Jares, A E Firor, X Shuai, H Salman, M Golightly, F Lan, L Senzel, L-H Leung, X Jiang, Y Ma
The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T cell acute lymphoblastic leukemia (T-ALL) and peripheral T cell lymphomas (PTCLs)...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28069604/kmt2e-asns-a-novel-relapse-specific-fusion-gene-in-early-t-cell-precursor-acute-lymphoblastic-leukemia
#3
Fida Khater, Mathieu Lajoie, Sylvie Langlois, Jasmine Healy, Sonia Cellot, Chantal Richer, Patrick Beaulieu, Pascal St-Onge, Virginie Saillour, Mark Minden, Monia Marzouki, Maja Krajinovic, Henrique Bittencourt, Daniel Sinnett
No abstract text is available yet for this article.
January 9, 2017: Blood
https://www.readbyqxmd.com/read/28069602/oncogenic-zeb2-activation-drives-sensitivity-towards-kdm1a-inhibition-in-t-cell-acute-lymphoblastic-leukemia
#4
Steven Goossens, Sofie Peirs, Wouter Van Loocke, Jueqiong Wang, Mina Takawy, Filip Matthijssens, Stefan E Sonderegger, Katharina Haigh, Thao Nguyen, Niels Vandamme, Magdaline Costa, Catherine Carmichael, Filip Van Nieuwerburgh, Dieter Deforce, Oded Kleifeld, David J Curtis, Geert Berx, Pieter Van Vlierberghe, Jody J Haigh
Elevated expression of the Zinc finger E-box binding homeobox transcription factor-2 (ZEB2) is correlated with poor prognosis and patient outcome in a variety of human cancer subtypes. Using a conditional gain-of-function mouse model, we recently demonstrated that ZEB2 is an oncogenic driver of immature T-cell acute lymphoblastic leukemia (T-ALL), a heterogenic subgroup of human leukemia characterized by a high incidence of remission failure or hematological relapse after conventional chemotherapy. Here, we identified the Lysine-specific demethylase KDM1A as a novel interaction partner of ZEB2 and demonstrated that mouse and human T-ALLs with increased ZEB2 levels critically depend on KDM1A activity for survival...
January 9, 2017: Blood
https://www.readbyqxmd.com/read/28063722/concordance-of-two-approaches-in-monitoring-of-minimal-residual-disease-in-b-precursor-acute-lymphoblastic-leukemia-fusion-transcripts-and-leukemia-associated-immunophenotypes
#5
Ying-Jung Huang, Elaine Coustan-Smith, Hsiao-Wen Kao, Hsi-Che Liu, Shih-Hsiang Chen, Chih-Cheng Hsiao, Chao-Ping Yang, Tang-Her Jaing, Ting-Chi Yeh, Ming-Chung Kuo, Chang-Liang Lai, Chia-Hui Chang, Dario Campana, Der-Cherng Liang, Lee-Yung Shih
BACKGROUND: Real-time quantitative polymerase chain reaction (RQ-PCR) for fusion transcripts and flow cytometry for leukemia-specific markers are widely used for minimal residual disease (MRD) detection in acute lymphoblastic leukemia, but the relation between the results of either method is unclear. METHODS: Mononucleated cells from 108 bone marrow samples collected from 55 B-precursor acute lymphoblastic leukemia patients (30 with t(12;21)/ETV6-RUNX1, 16 with t(9;22)/BCR-ABL1 and nine with t(1;19)/TCF3-PBX1) were examined in tandem by RQ-PCR and six-color flow cytometry...
January 4, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28060971/-intensity-adjustment-of-hematopoietic-alogeneic-transplantation-in-acute-leukemia
#6
Mauricio Sarmiento M, Pablo Bertín C, Verónica Jara, Mauricio Ocqueteau T, Pablo Ramírez V
BACKGROUND: The intensity of conditioning chemotherapy and radiotherapy in hematopoietic stem cell transplantation (HSCT) varies according to several factors including the patient’s age, pre-existing conditions and performance status. Myeloablative conditioning (MA) increases transplant related mortality and reduces survival in older patients. Reduced intensity conditioning (RIC) is a good option for these patients. AIM: To report our experience with HSCT in patients of different ages with acute leukemia...
September 2016: Revista Médica de Chile
https://www.readbyqxmd.com/read/28054944/the-role-of-histone-protein-modifications-and-mutations-in-histone-modifiers-in-pediatric-b-cell-progenitor-acute-lymphoblastic-leukemia
#7
REVIEW
Szymon Janczar, Karolina Janczar, Agata Pastorczak, Hani Harb, Adam J W Paige, Beata Zalewska-Szewczyk, Marian Danilewicz, Wojciech Mlynarski
While cancer has been long recognized as a disease of the genome, the importance of epigenetic mechanisms in neoplasia was acknowledged more recently. The most active epigenetic marks are DNA methylation and histone protein modifications and they are involved in basic biological phenomena in every cell. Their role in tumorigenesis is stressed by recent unbiased large-scale studies providing evidence that several epigenetic modifiers are recurrently mutated or frequently dysregulated in multiple cancers. The interest in epigenetic marks is especially due to the fact that they are potentially reversible and thus druggable...
January 3, 2017: Cancers
https://www.readbyqxmd.com/read/28053192/mature-cd10-and-immature-cd10-neutrophils-present-in-g-csf-treated-donors-display-opposite-effects-on-t-cells
#8
Olivia Marini, Sara Costa, Dalila Bevilacqua, Federica Calzetti, Nicola Tamassia, Cecilia Spina, Donata De Sabata, Elisa Tinazzi, Claudio Lunardi, Maria T Scupoli, Chiara Cavallini, Elisa Zoratti, Ilaria Tinazzi, Antonio Marchetta, Aurora Vassanelli, Maurizio Cantini, Giorgio Gandini, Andrea Ruzzenente, Alfredo Guglielmi, Francesco Missale, William Vermi, Cristina Tecchio, Marco A Cassatella, Patrizia Scapini
The identification of discrete neutrophil populations, as well as the characterization of their immunoregulatory properties, is an emerging topic under extensive investigation. In such regard, the presence of circulating CD66b(+)-neutrophil populations, exerting either immunosuppressive or proinflammatory functions, has been described in several acute and chronic inflammatory conditions. However, due to the lack of specific markers, the precise phenotype and maturation status of these neutrophil populations remain unclear...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28049548/chimeric-antigen-receptor-t-cell-neuropsychiatric-toxicity-in-acute-lymphoblastic-leukemia
#9
Vasthie Prudent, William S Breitbart
Chimeric antigen receptor T cells are used in the treatment of B-cell leukemias. Common chimeric antigen receptor T-cell toxicities can range from mild flu-like symptoms, such as fever and myalgia, to a more striking neuropsychiatric toxicity that can present as discrete neurological symptoms and delirium. We report here two cases of chimeric antigen receptor T-cell neuropsychiatric toxicity, one who presented as a mild delirium and aphasia that resolved without intervention, and one who presented with delirium, seizures, and respiratory insufficiency requiring intensive treatment...
January 4, 2017: Palliative & Supportive Care
https://www.readbyqxmd.com/read/28047771/su-g-tep3-07-on-the-development-of-mechano-biological-assessment-of-leukemia-cells-using-optical-tweezers
#10
E Brost, J Brooks, J Piepenburg, S Chakraborty, T Das, A Green, Y Watanabe, S Hui
PURPOSE: Patients with BCR-ABL (Ph +ve) acute lymphoblastic leukemia are at very high risk of relapse and mortality. In line with the NIH mission to understand the physical and biological processes, we seek to report mechano-biological method to assessment and distinguish treated/untreated leukemia cells. METHODS: BCR-ABL leukemia cell populations and silica microspheres were trapped in a 100x magnification optical trapping system (λ=660 nm, 70 mW). Light refracted through the trapped sample was collected in the back focal plane by a quadrant detector to measure the positions of individual cells...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28028314/redirecting-t-cells-to-eradicate-b-cell-acute-lymphoblastic-leukemia-bispecific-t-cell-engagers-and-chimeric-antigen-receptors
#11
REVIEW
I Aldoss, R C Bargou, D Nagorsen, G R Friberg, P A Baeuerle, S J Forman
Recent advances in antibody technology to harness T-cells for cancer immunotherapy, particularly in the difficult-to-treat setting of relapsed or refractory acute lymphoblastic leukemia (r/r ALL), has led to innovative methods for directing cytotoxic T-cells to specific surface antigens on cancer cells. One approach involves administration of soluble bispecific (or dual-affinity) antibody-based constructs that temporarily bridge T-cells and cancer cells. Another approach infuses ex vivo-engineered T-cells that express a surface plasma membrane-inserted antibody construct called a chimeric antigen receptor (CAR)...
December 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28028313/aberrant-activation-of-the-gimap-enhancer-by-oncogenic-transcription-factors-in-t-cell-acute-lymphoblastic-leukemia
#12
W-S Liau, S H Tan, P C T Ngoc, C Q Wang, V Tergaonkar, H Feng, Z Gong, M Osato, A T Look, T Sanda
The transcription factor TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic leukemia (T-ALL), a malignant disorder resulting from leukemic transformation of thymus T-cell precursors. TAL1 is normally expressed in hematopoietic stem cells (HSCs) but is silenced in immature thymocytes. We hypothesize that TAL1 contributes to leukemogenesis by activating genes that are normally repressed in immature thymocytes. Herein, we identified a novel TAL1-regulated super-enhancer controlling the GIMAP locus, which resides within an insulated chromosomal locus in T-ALL cells...
December 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28027552/state-of-erythroid-granulocyte-and-platelet-branches-of-hematopoiesis-on-stages-of-chemotherapy-in-children-with-acute-lymphoblastic-leukemia-who-were-exposed-to-ionizing-radiation-after-the-chornobyl-npp-accident
#13
V G Bebeshko, K M Bruslova, T I Pushkareva, N M Tsvyetkova, L O Lyashenko, O Ye Kuznyetsova, V F Kuzmenko, L O Gonchar, S M Yaatsemyrskyy
OBJECTIVE: Evaluation of proliferation and differentiation processes of progenitor cells in bone marrow by the com position of elements of erythroid, granulocyte and platelet branches of hematopoiesis on the treatment stages in children with acute lymphoblastic leukemia (ALL), who were exposed to radiation from the Chornobyl NPP accident. MATERIALS AND METHODS: The 46 children with ALL were studied, who lived in Kyiv, Zhytomyr and Chernihiv regions. Studies were conducted before the start of chemotherapy (ChT), on the 33 day of ChT (phase I), and after the com pletion of ChT (phase II)...
December 2016: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/28024476/-clinical-characteristics-and-prognosis-of-21-cases-of-acute-lymphoblastic-leukemia-with-central-nervous-system-leukemia
#14
Xiang-Shu Jin, Lan Yang, Bian-Hong Wang, Hong-Hua Li, Li Yu, Yu Jing
OBJECTIVE: To investigate the clinical characteristics, therapeutic efficacy survival and prognosis of patients with adult acute lymphoblastic leukemia (ALL) accompanied by central nervous system leukemia (CNSL). METHODS: The clinical and cerebrospinal fluid (CSF) features, diagnosis and treatment, therapeutic efficacy and survival rate of 21 cases of acute lymphoblastic leukemia (ALL) with central nervous system involvement (CNSL) were analyzed retrospectively...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28009354/rsk-mediated-nuclear-accumulation-of-the-cold-shock-y-box-protein-1-controls-proliferation-of-t-cells-and-t-all-blasts
#15
Steffi Gieseler-Halbach, Stefan Meltendorf, Mandy Pierau, Soenke Weinert, Florian H Heidel, Thomas Fischer, Juliane Handschuh, Ruediger C Braun-Dullaeus, Martin Schrappe, Jonathan A Lindquist, Peter R Mertens, Ulrich Thomas, Monika C Brunner-Weinzierl
Deregulated proliferation is key to tumor progression. Although unrestricted proliferation of solid tumor cells correlates with the cold-shock protein Y-box (YB)-binding protein-1 accumulation in the nuclei, little is known about its expression and function in hematopoietic malignancies, such as T-cell acute lymphoblastic leukemia (T-ALL). Here we show that YB-1 protein is highly enriched in the nuclei of activated T cells and malignant human T-ALL cell lines but not in resting T cells. YB-1 S(102) mutations that either mimic (S102D) or prevent phosphorylation (S102N) led to accumulation of YB-1 in the nucleus of T cells or strictly excluded it, respectively...
December 23, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28007775/beating-the-clock-in-t-cell-acute-lymphoblastic-leukemia
#16
William L Carroll, Iannis Aifantis, Elizabeth A Raetz
CDK4/6 inhibition was synergistic with dexmethasome and everolimus but antagonistic with conventional chemotherapy in T-cell acute lymphoblastic leukemia (T-ALL) pre-clinical models. Cyclin dependent kinase inhibition in combination with glucocorticoids and mTOR inhibition offers a unique therapeutic opportunity in T-ALL.
December 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28003999/synergistic-cytotoxic-effect-of-l-asparaginase-combined-with-decitabine-as-a-demethylating-agent-in-pediatric-t-all-with-specific-epigenetic-signature
#17
Salvatore Serravalle, Salvatore N Bertuccio, Annalisa Astolfi, Fraia Melchionda, Andrea Pession
T-Acute Lymphoblastic Leukemia (T-ALL) remains a subgroup of pediatric ALL, with a lower response to standard chemotherapy. Some recent studies established the fundamental role of epigenetic aberrations such as DNA hypermethylation, to influence patients' outcome and response to chemotherapy. Moreover, L-asparaginase is an important chemotherapeutic agent for treatment of ALL and resistance to this drug has been linked to ASNS expression, which can be silenced through methylation. Therefore, we tested whether the sensitivity of T-ALL cell lines towards L-asparaginase is correlated to the epigenetic status of ASNS gene and whether the sensitivity can be modified by concurrent demethylating treatment...
2016: BioMed Research International
https://www.readbyqxmd.com/read/28003275/tp53-mutations-in-hypodiploid-acute-lymphoblastic-leukemia
#18
Evan Q Comeaux, Charles G Mullighan
Acute lymphoblastic leukemia (ALL) is an aggressive neoplasm of B- or T-lymphoid progenitors and is the commonest childhood tumor. ALL comprises multiple subtypes characterized by distinct genetic alterations, with stereotyped patterns of aneuploidy present in many cases. Although alterations of TP53 are common in many tumors, they are infrequent in ALL, with the exception of two ALL subtypes associated with poor outcome: relapsed disease and ALL with hypodiploidy. TP53 alterations are present in almost all cases of ALL with low hypodiploidy and are associated with alterations of the lymphoid transcription factor IKZF2 and the tumor-suppressor gene loci CDKN2A and CDKN2B...
December 21, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28002337/anti-cd19-chimeric-antigen-receptor-t-cell-therapy-for-adult-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-two-case-reports
#19
Yang-Min Zhu, Zhao Wu, You-Ping Tan, Yuan-Yuan Du, Zhi Liu, Rui-Ming Ou, Shuang Liu, Cheng-Fei Pu, Jing Jiang, Jin-Ping Wang, Lei Xiao, Qing Zhang
RATIONALE: The presence of the Philadelphia chromosome (Ph) in acute lymphoblastic leukemia (ALL) has been associated with a high risk of disease relapse and a poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT) is an established treatment for adults with Ph-positive ALL, but relapse remains the primary cause of treatment failure, and is associated with an extremely poor prognosis. The emergence of resistance to tyrosine kinase inhibitors (TKIs) poses a challenge for patients with disease relapses after initial treatment with TKI-containing regimens...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28000876/mir-196b-mir-1290-participate-in-the-antitumor-effect-of-resveratrol-via-regulation-of-igfbp3-expression-in-acute-lymphoblastic-leukemia
#20
Wei Zhou, Shunqing Wang, Yi Ying, Ruiqing Zhou, Ping Mao
MicroRNAs play critical roles in the progression of acute lymphoblastic leukemia (ALL). Previous studies have indicated that miR-196b and miR-1290 play critical roles in T-cell ALL (T-ALL) and B-cell ALL (B-ALL), respectively. Resveratrol, a natural edible polyphenolic phytoalexin, possesses certain anticancer activities. Nevertheless, the mechanism involved in the regulation of ALL by resveratrol is still poorly understood. The present study aimed to reveal the potential mechanism underlying the antitumor effect of resveratrol in ALL focusing on miRNAs...
December 15, 2016: Oncology Reports
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