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https://www.readbyqxmd.com/read/28819280/results-of-nopho-all2008-treatment-for-patients-1-45-years-with-acute-lymphoblastic-leukemia
#1
N Toft, H Birgens, J Abrahamsson, L Griškevičius, H Hallböök, M Heyman, T W Klausen, Ó G Jónsson, K Palk, K Pruunsild, P Quist-Paulsen, G Vaitkeviciene, K Vettenranta, A Åsberg, T L Frandsen, H V Marquart, H O Madsen, U Norén-Nyström, K Schmiegelow
Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. 1022 patients were 1-9 years (A), 266 were 10-17 years (B), and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1...
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28813523/et-26-hydrochloride-et-26-hcl-has-similar-hemodynamic-stability-to-that-of-etomidate-in-normal-and-uncontrolled-hemorrhagic-shock-uhs-rats
#2
Bin Wang, Shouming Chen, Jun Yang, Linghui Yang, Jin Liu, Wensheng Zhang
OBJECTIVE: ET-26 HCl is a promising sedative-hypnotic anesthetic with virtually no effect on adrenocortical steroid synthesis. However, whether or not ET-26 HCl also has a sufficiently wide safety margin and hemodynamic stability similar to that of etomidate and related compounds remains unknown. In this study, the effects of ET-26 HCl, etomidate and propofol on therapeutic index, heart rate (HR), mean arterial pressure (MAP), maximal rate for left ventricular pressure rise (Dmax/t), and maximal rate for left ventricular pressure decline (Dmin/t) were investigated in healthy rats and a rat model of uncontrolled hemorrhagic shock (UHS)...
2017: PloS One
https://www.readbyqxmd.com/read/28811712/association-between-cyp24a1-polymorphisms-and-the-risk-of-colonic-polyps-and-colon-cancer-in-a-chinese-population
#3
Xue-Qi Chen, Jia-Yu Mao, Wen-Bin Li, Jian Li, Hong Yang, Jia-Ming Qian, Jing-Nan Li
AIM: To determine the pathogenesis and potential single nucleotide polymorphisms (SNPs) as screening sites for colonic polyps, colon cancer and ulcerative colitis, and to analyze the possible association between these genetic polymorphisms and the three diseases. METHODS: We evaluated genetic polymorphisms in 144 newly diagnosed colonic polyp patients, 96 colon cancer patients and 44 ulcerative colitis patients. The four SNPs genotyped were rs4809957, rs6068816, rs6091822 and rs8124792...
July 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28802664/cytokines-and-soluble-hla-g-levels-in-bone-marrow-stroma-and-their-association-with-the-survival-rate-of-patients-exhibiting-childhood-t-cell-acute-lymphoblastic-leukemia
#4
Renata Dos Santos Almeida, Alessandra Maria de Luna Ramos, Carlos Feitosa Luna, Francisco Pedrosa, Eduardo Antônio Donadi, Norma Lucena-Silva
Leukemic cells can induce defective expression of soluble factors and change marrow cytokine profile, leading to aberrant cell signaling, cell fixation and cell proliferation in bone marrow. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disorder which accounts for 15% of pediatric ALL. To evaluate the contribution of immunological factors on T-ALL survival, we measured Th1, Th2, Th17 cytokines and soluble HLA-G (sHLA-G) levels in bone marrow from 32 Brazilian children at diagnosis (D0), after induction (D19) and after consolidation (D49) of the chemotherapy phase...
August 9, 2017: Cytokine
https://www.readbyqxmd.com/read/28801656/comprehensive-mirna-expression-profiling-in-human-t-cell-acute-lymphoblastic-leukemia-by-small-rna-sequencing
#5
Annelynn Wallaert, Wouter Van Loocke, Lucie Hernandez, Tom Taghon, Frank Speleman, Pieter Van Vlierberghe
T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease that can be classified into different molecular genetic subtypes according to their mRNA gene expression profile. In this study, we applied RNA sequencing to investigate the full spectrum of miRNA expression in primary T-ALL patient samples, T-ALL leukemia cell lines and healthy donor thymocytes. Notably, this analysis revealed that genetic subtypes of human T-ALL also display unique miRNA expression signatures, which are largely conserved in human T-ALL cell lines with corresponding genetic background...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28792162/immunological-subtypes-of-acute-lymphoblastic-leukemia-beyond-morphology-experience-from-kidwai-state-cancer-institute-bengaluru-india
#6
Namrata N Rajkumar, Raghavendra H Vijay
INTRODUCTION: Acute lymphoblastic leukemia (ALL) is disease of lymphoid precursors and is the most common cancer. Diagnosis of ALL is made by evaluating morphology and flowcytometric Immunophenotyping (FCI)and is an important adjunct in diagnosis and determining treatment in ALL, with availability of extensive monoclonal antibodies in the recent years there is tremendous progress in the field of FCI, and is a requirement by World Health Organisation for the classification of acute lymphoblastic Leukemia...
July 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28790107/runx1-is-required-for-oncogenic-myb-and-myc-enhancer-activity-in-t-cell-acute-lymphoblastic-leukemia
#7
AHyun Choi, Anuradha Illendula, John A Pulikkan, Justine E Roderick, Jessica Tesell, Jun Yu, Nicole Hermance, Lihua Julie Zhu, Lucio H Castilla, John H Bushweller, Michelle A Kelliher
The gene encoding the RUNX1 transcription factor is mutated in a subset of T cell acute lymphoblastic leukemia (T-ALL) patients and RUNX1 mutations are associated with a poor prognosis. These mutations cluster in the DNA binding Runt domain, are thought to represent loss-of-function mutations, indicating that RUNX1 suppresses T cell transformation. RUNX1 has been proposed to have tumor suppressor roles in TLX1/3 transformed human T-ALL cell lines and NOTCH1 T-ALL mouse models. Yet retroviral insertional mutagenesis screens identify RUNX genes as collaborating oncogenes in MYC-driven leukemia mouse models...
August 8, 2017: Blood
https://www.readbyqxmd.com/read/28771663/safety-and-efficacy-of-nelarabine-in-children-and-young-adults-with-relapsed-or-refractory-t-lineage-acute-lymphoblastic-leukaemia-or-t-lineage-lymphoblastic-lymphoma-results-of-a-phase-4-study
#8
Christian Michel Zwaan, Jerzy Kowalczyk, Claudine Schmitt, Bella Bielorai, Mark W Russo, Mary Woessner, Sulabha Ranganathan, Guy Leverger
Nelarabine is an antineoplastic agent approved for the treatment of relapsed/refractory T-lineage acute lymphoblastic leukaemia (T-ALL) or T-lineage acute lymphoblastic lymphoma (T-LBL). The purpose of this phase 4, multicentre, single-arm, observational, open-label trial was to provide additional data on the safety and efficacy of nelarabine under licensed conditions of use in children and young adults ≤21 years of age. Patients (N = 28) had a mean ± standard deviation age of 11·5 ± 4·6 years; 71% were male and 61% had a diagnosis of T-ALL...
August 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28771662/neurotoxic-side-effects-in-children-with-refractory-or-relapsed-t-cell-malignancies-treated-with-nelarabine-based-therapy
#9
Michaela Kuhlen, Kirsten Bleckmann, Anja Möricke, Martin Schrappe, Simon Vieth, Gabriele Escherich, Annika Bronsema, Annika Vonalt, Manon Queudeville, C Michel Zwaan, Martin Ebinger, Klaus-Michael Debatin, Thomas Klingebiel, Ewa Koscielniak, Claudia Rossig, Birgit Burkhardt, Reinhard Kolb, Cornelia Eckert, Arndt Borkhardt, Arend von Stackelberg, Christiane Chen-Santel
The prognosis in children with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia (T-ALL) or lymphoblastic lymphoma (T-LBL) is poor. Nelarabine (Ara-G) has successfully been used as salvage therapy in these children, but has been associated with significant, even fatal, neurotoxicities. We retrospectively analysed 52 patients with r/r T-ALL/T-LBL aged ≤19 years who were treated with Ara-G alone (n = 25) or in combination with cyclophosphamide and etoposide (n = 27). The majority of patients (45/52) received 1-2 cycles of Ara-G...
August 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28768246/interim-pet-ct-may-predict-pfs-and-os-in-t-all-lbl-adult-patients
#10
Liang Wang, Jing-Hua Wang, Xi-Wen Bi, Xiao-Qin Chen, Yue Lu, Zhong-Jun Xia
T lymphoblastic leukemia/lymphoma (T-ALL/LBL) is highly aggressive. Although intensive chemotherapies such as ALL-type regimens are commonly used, about half adult patients eventually relapse and die of T-ALL/LBL. Overwhelming evidences have confirmed that interim PET can predict survival outcomes and guide subsequent treatments in Hodgkin lymphoma. However, whether interim PET-CT can predict survival outcomes or not in T-ALL/LBL patients remains unclear. 47 adult patients of T-ALL/LBL were retrospectively reviewed...
July 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28756008/efficacy-of-the-cdk-inhibitor-dinaciclib-in%C3%A2-vitro-and-in%C3%A2-vivo-in-t-cell-acute-lymphoblastic-leukemia
#11
Sausan A Moharram, Kinjal Shah, Fatima Khanum, Alissa Marhäll, Mohiuddin Gazi, Julhash U Kazi
T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease of the blood affecting children, adolescents and adults. Although current treatment protocols for T-ALL have improved overall survival, a portion of T-ALL patients still experiences treatment failure. Thus, the development of novel therapies is needed. In this study, we used several patient-derived T-ALL cell lines to screen for an effective drug for T-ALL. Using a panel of 378 inhibitors against different kinases, we identified the CDK inhibitor dinaciclib as a potential drug for T-ALL...
July 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28752543/exonal-switch-down-regulates-the-expression-of-cd5-on-blasts-of-acute-t-cell-leukemia
#12
Ambak Kumar Rai, Amar Singh, Ankit Saxena, Tulika Seth, Vinod Raina, Dipendra Kumar Mitra
CD5 expression and its role in acute T cell lymphoblastic leukemia (T-ALL) have not been elaborately studied so far. We observed a significant reduction in surface expression of CD5 (sCD5) on leukemic T cells compared to autologous non-leukemic T cells. In this study, we have shown the molecular mechanism regulating the expression and function of CD5 on leukemic T cells. Total 250 numbers of patients suffering from leukemia and lymphoma were immunophenotyped. Final diagnosis was based on their clinical presentation, morphological data and flowcytometry based immunophenotyping...
July 28, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28745456/pediatric-t-all-complicated-by-irreversible-nelarabine-neurotoxicity
#13
Takuyo Kanayama, Toshihiko Imamura, Norio Nakagawa, Shinya Osone, Hajime Hosoi
No abstract text is available yet for this article.
July 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28744013/the-t-cell-leukemia-associated-ribosomal-rpl10-r98s-mutation-enhances-jak-stat-signaling
#14
T Girardi, S Vereecke, S O Sulima, Y Khan, L Fancello, J W Briggs, C Schwab, J O de Beeck, J Verbeeck, J Royaert, E Geerdens, C Vicente, S Bornschein, C J Harrison, J P Meijerink, J Cools, J D Dinman, K R Kampen, K De Keersmaecker
Several somatic ribosome defects have recently been discovered in cancer, yet their oncogenic mechanisms remain poorly understood. Here we investigated the pathogenic role of the recurrent R98S mutation in ribosomal protein L10 (RPL10-R98S) found in T-ALL. The JAK-STAT signaling pathway is a critical controller of cellular proliferation and survival. A proteome screen revealed overexpression of several Jak-Stat signaling proteins in engineered RPL10-R98S mouse lymphoid cells, which we confirmed in hematopoietic cells from transgenic Rpl10-R98S mice and T-ALL xenograft samples...
July 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28736882/the-clinical-significance-of-monitoring-the-expression-of-the-sil-tal1-fusion-gene-in-t-cell-acute-lymphoblastic-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#15
X Zhao, Y Hong, Y Qin, Y Xu, Y Chang, Y Wang, X Zhang, L Xu, X Huang
INTRODUCTION: SIL-TAL1 rearrangement is common in T-cell acute lymphoblastic leukemia (T-ALL). However, whether this fusion gene might be used as a reliable marker of minimal residual disease (MRD) following allogeneic stem cell transplantation (allo-HSCT) remains unknown METHODS: The clinical data of consecutive 29 patients with T-ALL who received allo-HSCT were collected. Their MRD were evaluated by SIL-TAL1, Wilms' tumor 1 (WT1) expression, and the leukemia-associated immunophenotype (LAIP) ...
July 24, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28723644/fir-haplodeficiency-promotes-splicing-to-pyruvate-kinase-m2-in-mice-thymic-lymphoma-tissues-revealed-by-six-plex-tandem-mass-tag-quantitative-proteomic-analysis
#16
Asako Kimura, Kouichi Kitamura, Guzhanuer Ailiken, Mamoru Satoh, Toshinari Minamoto, Nobuko Tanaka, Fumio Nomura, Kazuyuki Matsushita
The switch of pyruvate kinase (PK) M1 to PKM2 is pivotal for glucose metabolism in cancers. The PKM1/M2 shift is controlled by the alternative splicing of two mutually exclusive exons in the PKM gene. PKM1 is expressed in differentiated tissues, whereas PKM2 is expressed in cancer tissues. This study revealed that the haplodeficiency of FUSE-binding protein (FBP)-interacting repressor (FIR), a transcriptional repressor of the c-myc gene, contributed to the splicing of PKM1 to PKM2 in mice thymic lymphoma and/or T-cell type acute lymphoblastic leukemia (T-ALL) using six-plex tandem mass tag (TMT) quantitative proteomic analysis...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722319/immunophenotypic-aberrancies-in-acute-lymphoblastic-leukemia-from-282-iraqi-patients
#17
S D Jalal, N A S Al-Allawi, A A S Al Doski
INTRODUCTION: The identification of aberrancies in leukemia-associated immunophenotype (LAIP) of acute lymphoblastic leukemia (ALL) is quite important in the assessment of minimal residual disease (MRD). This study, the first from Iraq, aimed to assess the frequency and patterns of LAIP among Iraqi patients with ALL, to establish future strategies for evaluating MRD. METHODS: A total of 282 newly diagnosed Iraqi ALL cases were analyzed with six-parameter flow cytometry using a panel of 29 monoclonal antibodies...
July 18, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28719899/the-relationship-between-mmp-2-1306c-t-and-mmp-9-1562c-t-polymorphisms-and-the-risk-and-prognosis-of-t-cell-acute-lymphoblastic-leukemia-in-a-chinese-population-a-case-control-study
#18
Cong-Meng Lin, Yan-Ling Zeng, Min Xiao, Xu-Qiao Mei, Lv-Ying Shen, Meng-Xian Guo, Zhe-Yao Lin, Qi-Fa Liu, Tin Yang
BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disease and is often accompanied by a variety of genetic abnormalities. Hence, our study aims to investigate the relationship between MMP-2 -1306C>T and MMP-9 -1562C>T polymorphisms and the risk and prognosis of T-ALL. METHODS: From April 2009 to February 2011, a total of 376 T-ALL patients were chosen as the case group. Meanwhile, 352 healthy people who passed routine health examinations were selected as the control group...
July 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28716817/pi3k-gamma-delta-and-notch1-cross-regulate-pathways-that-define-the-t-cell-acute-lymphoblastic-leukemia-disease-signature
#19
Evgeni Efimenko, Utpal P Davé, Irina V Lebedeva, Yao Shen, Maria J Sanchez-Quintero, Daniel Diolaiti, Andrew Kung, Brian J Lannutti, Jianchung Chen, Ronald Realubit, Zoya Niatsetskiya, Vadim Ten, Charles Karan, Xi Chen, Andrea Califano, Thomas G Diacovo
PI3K/AKT and NOTCH1 signaling pathways are frequently dysregulated in T-cell acute lymphoblastic leukemias (T-ALL). Although we have shown that the combined activities of the class I PI3K isoforms p110γ and p110δ play a major role in the development and progression of PTEN null T-ALL, it has yet to be determined whether their contribution to leukemogenic programing is unique from that associated with NOTCH1 activation. Using a Lmo2-driven mouse model of T-ALL in which both the PI3K/AKT and NOTCH1 pathways are aberrantly upregulated, we now demonstrate that the combined activities of PI3Kγ/δ have both overlapping and distinct roles from NOTCH1 in generating T-ALL disease signature and in promoting tumor cell growth...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28715419/the-t-cell-leukemia-related-rpl10-r98s-mutant-traps-the-60s-export-adapter-nmd3-in-the-ribosomal-p-site-in-yeast
#20
Stephanie Patchett, Sharmishtha Musalgaonkar, Andrey G Malyutin, Arlen W Johnson
Mutations in the ribosomal protein Rpl10 (uL16) can be drivers of T-cell acute lymphoblastic leukemia (T-ALL). We previously showed that these T-ALL mutations disrupt late cytoplasmic maturation of the 60S ribosomal subunit, blocking the release of the trans-acting factors Nmd3 and Tif6 in S. cerevisiae. Consequently, these mutant ribosomes do not efficiently pass the cytoplasmic quality control checkpoint and are blocked from engaging in translation. Here, we characterize suppressing mutations of the T-ALL-related rpl10-R98S mutant that bypass this block and show that the molecular defect of rpl10-R98S is a failure to release Nmd3 from the P site...
July 2017: PLoS Genetics
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