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https://www.readbyqxmd.com/read/27913532/t-cell-acute-lymphoblastic-leukemia
#1
Elizabeth A Raetz, David T Teachey
T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27902457/tfdp3-confers-chemoresistance-in-minimal-residual-disease-within-childhood-t-cell-acute-lymphoblastic-leukemia
#2
Ming Chu, Kailin Yin, Yujun Dong, Pingzhang Wang, Yun Xue, Peng Zhou, Yuqi Wang, Yuedan Wang
Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered: TFDP3 increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX), L-asparaginase (L-asp) and daunorubicin (DNR)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899804/casein-kinase-2-controls-the-survival-of-normal-thymic-and-leukemic-%C3%AE-%C3%AE-t-cells-via-promotion-of-akt-signaling
#3
S T Ribeiro, M Tesio, J C Ribot, E Macintyre, J T Barata, B Silva-Santos
The thymus is the major site for normal and leukemic T-cell development. The dissection of the molecular determinants of T-cell survival and differentiation is paramount for the manipulation of healthy or transformed T cells in cancer (immuno)therapy. Casein Kinase 2 (CK2) is a serine-threonine protein kinase whose anti-apoptotic functions have been described in various hematological and solid tumors. Here we disclose an unanticipated role of CK2 in healthy human thymocytes that is selective to the γδ T-cell lineage...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27895788/effects-of-microrna-21-on-the-biological-functions-of-t-cell-acute-lymphoblastic-lymphoma-leukemia
#4
Cunzhen Shi, Xudong Zhang, Xin Li, Lei Zhang, Ling Li, Zhenchang Sun, Xiaorui Fu, Jingjing Wu, Yu Chang, Wencai Li, Qingjiang Chen, Mingzhi Zhang
Previous studies have demonstrated that microRNA-21 (miR-21) is an oncogene and is significantly upregulated in tumor tissue. However, its association with T-cell acute lymphoblastic lymphoma/leukemia (T-ALL) remains poorly understood. The aim of the present study was to investigate the effects of miR-21 on T-ALL cells by constructing Jurkat cells infected with recombinant adenovirus adv-miR-21 or adv-anti-miR-21. In addition, the target gene of miR-21 was identified by reverse transcription-quantitative polymerase chain reaction and western blotting...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27881872/in-vitro-and-in-vivo-assessment-of-direct-effects-of-simulated-solar-and-galactic-cosmic-radiation-on-human-hematopoietic-stem-progenitor-cells
#5
C Rodman, G Almeida-Porada, S George, J Moon, S Soker, T Pardee, M Beaty, P Guida, S P Sajuthi, C D Langefeld, S J Walker, P F Wilson, C D Porada
Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation, and likely one or more solar particle events (SPEs). Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions. We show that exposing human hematopoietic stem/progenitor cells (HSC) to extended mission-relevant doses of accelerated high-energy protons and iron ions: 1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; 2) dramatically reduces in vitro colony-formation; 3) markedly alters engraftment and lineage commitment in vivo; and 4) leads to the development, in vivo, of what appears to be T-ALL...
November 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27875783/prame-overexpression-predicted-good-outcome-in-pediatric-b-cell-acute-lymphoblastic-leukemia-patients-receiving-chemotherapy
#6
Yan-Huan Zhang, Ai-Dong Lu, Lu Yang, Ling-Di Li, Wen-Min Chen, Ling-Yu Long, Le-Ping Zhang, Ya-Zhen Qin
To investigate the prognostic value of PRAME expression in pediatric acute lymphoblastic leukemia(ALL), we measured PRAME transcript levels at diagnosis in 191 patients(146 B-ALL; 45T-ALL)receiving chemotherapy only. PRAME overexpression was defined as transcript levels higher than 0.30%, which is the upper limit of normal bone marrow and the optimal cutoff value derived from ROC curve analysis. PRAME overexpression was identified in 45.5% of patients. In B-ALL, PRAME overexpression was significantly associated with lower CIR(cumulative incidence of relapse), higher DFS (disease-freesurvival), and OS(overall survival) rates at 3 years, respectively (5...
November 11, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27872496/inactivation-of-klf4-promotes-t-cell-acute-lymphoblastic-leukemia-and-activates-the-map2k7-pathway
#7
Y Shen, C S Park, K Suppipat, T-A Mistretta, M Puppi, T Horton, K Rabin, N S Gray, J P P Meijerink, H D Lacorazza
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a high incidence of relapse in pediatric ALL. Although most T-ALL patients exhibit activating mutations in NOTCH1, the cooperating genetic events required to accelerate the onset of leukemia and worsen disease progression are largely unknown. Here, we show that the gene encoding the transcription factor KLF4 is inactivated by DNA methylation in children with T-ALL. In mice, loss of KLF4 accelerated the development of NOTCH1-induced T-ALL by enhancing the G1-to-S transition in leukemic cells and promoting the expansion of leukemia-initiating cells...
November 22, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27869523/nelarabine-in-the-treatment-of-pediatric-and-adult-patients-with-t-cell-acute-lymphoblastic-leukemia-and-lymphoma
#8
Tapan M Kadia, Varsha Gandhi
Introduction T-cell acute lymphoblastic leukemia (ALL) and lymphoma (LBL) are aggressive hematologic neoplasms that are treated with combination chemotherapy in the frontline, but have limited options in the relapsed or refractory setting. Based on observations in patients with purine nucleoside phosphorylase (PNP) deficiency, a guanosine nucleoside analogue, arabinosylguanine (ara-G) was developed that provided T-cell specificity. Nelarabine was developed as the water-soluble, clinically useful-prodrug of ara-G and based on its activity was approved for the treatment of relapsed or refractory T-ALL/LBL...
November 21, 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27849437/optimum-temperature-of-oxygen-for-transpulmonary-hypothermia-with-cooled-oxygen-inhalation-a-preliminary-study-in-a-rat-model
#9
Banu Karakus Yilmaz, Hatice Topcu, Yahya A Acar, Duygu Sultan Oran, Sule Ozsoy, Erdem Çevik, Aylin Hakligor, Orhan Çinar
Cooled oxygen inhalation was hypothesized as a novel hypothermia technique in a previous study. In the current study, we aimed to determine the optimal temperature of oxygen for this method. This is a prospective, randomized, controlled, examiner-blinded experimental study conducted with 45 healthy, adult, Wistar Hannover male rats. Rats were randomly divided into five groups; group 1: +4°C intubated group (n = 7), group 2: +4°C nonintubated group (n = 9), group 3: +8°C intubated group (n = 9), group 4: +8°C nonintubated group (n = 9), and group 5: control group (n = 9)...
November 16, 2016: Therapeutic Hypothermia and Temperature Management
https://www.readbyqxmd.com/read/27835864/senescent-stromal-cell-induced-divergence-and-therapeutic-resistance-in-t-cell-acute-lymphoblastic-leukemia-lymphoma
#10
David M Habiel, Nicolas Krepostman, Michael Lilly, Karen Cavassani, Ana Lucia Coelho, Takehiko Shibata, Kojo Elenitoba-Johnson, Cory M Hogaboam
T cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL/LBL) is a precursor T cell leukemia/lymphoma that represents approximately 15% of all childhood and 25% of adult acute lymphoblastic leukemia. Although a high cure rate is observed in children, therapy resistance is often observed in adults and mechanisms leading to this resistance remain elusive. Utilizing public gene expression datasets, a fibrotic signature was detected in T-LBL but not T-ALL biopsies. Further, using a T-ALL cell line, CCRF-CEM (CEM) cells, we show that CEM cells induce pulmonary remodeling in immunocompromised mice, suggesting potential interaction between these cells and lung fibroblasts...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27831567/erk-drp1-dependent-mitochondrial-fission-is-involved-in-the-msc-induced-drug-resistance-of-t-cell-acute-lymphoblastic-leukemia-cells
#11
Jianye Cai, Jiancheng Wang, Yinong Huang, Haoxiang Wu, Ting Xia, Jiaqi Xiao, Xiaoyong Chen, Hongyu Li, Yuan Qiu, Yingnan Wang, Tao Wang, Huimin Xia, Qi Zhang, Andy Peng Xiang
The bone marrow microenvironment facilitates the proliferation and survival of leukemia cells, contributing to disease relapse. Bone marrow-derived mesenchymal stem cells (MSCs) are well known to promote cancer chemoresistance via soluble factors and cell adhesion. However, little is known about the effects of MSCs on the mitochondrial dynamics of T-cell acute lymphoblastic leukemia (T-ALL) cells, or how this may influence the chemoresistance of these cells. Here, we tested both indirect (Transwell) and direct coculture strategies, and found that MSCs protected T-ALL cells from chemotherapeutic cell death and cytotoxicity under both culture conditions...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27826566/variations-in-mrna-and-protein-levels-of-ikaros-family-members-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#12
Julie L Mitchell, Thomas M Yankee
BACKGROUND: Pediatric T cell acute lymphoblastic leukemia (T-ALL) is a highly heterogeneous disease in which the cells share phenotypic characteristics with normal human thymocytes. The Ikaros family of transcription factors includes five members that are required for normal T cell development and are implicated in leukemogenesis. The goal of this work was to correlate the pattern of expression of Ikaros family members with the phenotype of the T-ALL cells. METHODS: We obtained twenty-four samples from pediatric T-ALL patients and used multi-parameter flow cytometry to characterize each sample, comparing the phenotype of the leukemic cells with normal human thymocytes...
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27824040/t-all-several-homes-rather-than-homeless
#13
Justyna Rak, Simón Méndez-Ferrer
No abstract text is available yet for this article.
November 8, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27822711/the-complete-mitogenome-of-a-jumping-spider-carrhotus-xanthogramma-araneae-salticidae-and-comparative-analysis-in-four-salticid-mitogenomes
#14
Wen-Yuan Fang, Zheng-Liang Wang, Chao Li, Xiao-Qing Yang, Xiao-Ping Yu
The complete mitogenome of the jumping spider Carrhotus xanthogramma was determined and comparative analysis among four salticid mitogenomes was conducted. The circular genome is 14,563 bp in size and contains a complete set of genes that usually present in the metazoa. All of the 13 protein-coding genes begin with a typical ATN codon and stop with the canonical stop codons, except for ND4 and ND4L genes with an incomplete stop codon T. All of the tRNAs cannot be formed the fully paired acceptor stems and seven out of them cannot be folded into the typical cloverleaf-shaped secondary structures...
December 2016: Genetica
https://www.readbyqxmd.com/read/27821800/synergistic-effects-of-selective-inhibitors-targeting-the-pi3k-akt-mtor-pathway-or-nup214-abl1-fusion-protein-in-human-acute-lymphoblastic-leukemia
#15
Carolina Simioni, Simona Ultimo, Alberto M Martelli, Giorgio Zauli, Daniela Milani, James A McCubrey, Silvano Capitani, Luca M Neri
Philadelphia chromosome-positive (Ph+) Acute Lymphoblastic Leukemia (ALL) accounts for 25-30% of adult ALL and its incidence increases with age in adults >40 years old. Irrespective of age, the ABL1 fusion genes are markers of poor prognosis and amplification of the NUP214-ABL1 oncogene can be detected mainly in patients with T-ALL. T cell malignancies harboring the ABL1 fusion genes are sensitive to many cytotoxic agents, but up to date complete remissions have not been achieved. The PI3K/Akt/mTOR signaling pathway is often activated in leukemias and plays a crucial role in leukemogenesis...
November 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27820136/paraneoplastic-galactorrhea-in-childhood-t-all-an-evaluation-of-tumor-derived-prolactin
#16
Allison Grimes, Nooshin Mirkheshti, Bandana Chatterjee, Gail Tomlinson, Chatchawin Assanasen
T-cell acute lymphoblastic leukemia (T-ALL) comprises 15% of childhood leukemia. Although multiagent pulse chemotherapy has improved event-free survival in recent decades, the lack of reliable prognosticators and high rate of relapse remain a challenge. Described is a novel discovery of tumor-derived hyperprolactinemia in childhood T-ALL through a case associated with paraneoplastic galactorrhea. Prolactin production by tumor cells, although a rare phenomenon, is previously demonstrated in several adult cancers and 2 pediatric malignancies with unknown implications...
November 4, 2016: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27797342/high-throughput-screening-in-niche-based-assay-identifies-compounds-to-target-preleukemic-stem-cells
#17
Bastien Gerby, Diogo F T Veiga, Jana Krosl, Sami Nourreddine, Julianne Ouellette, André Haman, Geneviève Lavoie, Iman Fares, Mathieu Tremblay, Véronique Litalien, Elizabeth Ottoni, Milena Kosic, Dominique Geoffrion, Joël Ryan, Paul S Maddox, Jalila Chagraoui, Anne Marinier, Josée Hébert, Guy Sauvageau, Benjamin H Kwok, Philippe P Roux, Trang Hoang
Current chemotherapies for T cell acute lymphoblastic leukemia (T-ALL) efficiently reduce tumor mass. Nonetheless, disease relapse attributed to survival of preleukemic stem cells (pre-LSCs) is associated with poor prognosis. Herein, we provide direct evidence that pre-LSCs are much less chemosensitive to existing chemotherapy drugs than leukemic blasts because of a distinctive lower proliferative state. Improving therapies for T-ALL requires the development of strategies to target pre-LSCs that are absolutely dependent on their microenvironment...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27783382/short-term-effects-of-neuromuscular-blockade-on-global-and-regional-lung-mechanics-oxygenation-and-ventilation-in-pediatric-acute-hypoxemic-respiratory-failure
#18
Marlon E F Wilsterman, Pauline de Jager, Robert Blokpoel, Inez Frerichs, Sandra K Dijkstra, Marcel J I J Albers, Johannes G M Burgerhof, Dick G Markhorst, Martin C J Kneyber
BACKGROUND: Neuromuscular blockade (NMB) has been shown to improve outcome in acute respiratory distress syndrome (ARDS) in adults, challenging maintaining spontaneous breathing when there is severe lung injury. We tested in a prospective physiological study the hypothesis that continuous administration of NMB agents in mechanically ventilated children with severe acute hypoxemic respiratory failure (AHRF) improves the oxygenation index without a redistribution of tidal volume V T toward non-dependent lung zones...
December 2016: Annals of Intensive Care
https://www.readbyqxmd.com/read/27778145/splenic-rupture-and-mediastinal-mass-associated-with-rare-tdt-negative-t-lbl-t-all-lead-to-sudden-death-of-a-juvenile
#19
Dominic Gascho, Bettina Huber, Stephan A Bolliger, Michael J Thali, Sarah Schaerli
No abstract text is available yet for this article.
October 24, 2016: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/27776559/improving-nelarabine-efficacy-in-t-cell-acute-lymphoblastic-leukemia-by-targeting-aberrant-pi3k-akt-mtor-signaling-pathway
#20
Annalisa Lonetti, Alessandra Cappellini, Alice Bertaina, Franco Locatelli, Andrea Pession, Francesca Buontempo, Camilla Evangelisti, Cecilia Evangelisti, Ester Orsini, Laura Zambonin, Luca Maria Neri, Alberto Maria Martelli, Francesca Chiarini
BACKGROUND: Although in recent years, the introduction of novel chemotherapy protocols has improved the outcome of T cell acute lymphoblastic leukemia (T-ALL) patients, refractory and/or relapsing disease remains a foremost concern. In this context, a major contribution was provided by the introduction of the nucleoside analog nelarabine, approved for salvage treatment of T-ALL patients with refractory/relapsed disease. However, nelarabine could induce a life-threatening, dose-dependent neurotoxicity...
October 24, 2016: Journal of Hematology & Oncology
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