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T-cell acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/28811744/cytogenetic-profile-and-flt3-gene-mutations-of-childhood-acute-lymphoblastic-leukemia
#1
Nawaf Alkhayat, Yasser Elborai, Omer Al Sharif, Mohammad Al Shahrani, Omar Alsuhaibani, Mohammed Awad, Hatem Elghezal, Inesse Ben-Abdallah Bouhajar, Mona Alfaraj, Eman Al Mussaed, Fahad Alabbas, Ghaleb Elyamany
BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent genetic aberrations. The identification of those abnormalities is clinically important because they are considered significant risk-stratifying markers. AIMS: There are insufficient data of cytogenetic profiles in Saudi Arabian patients with childhood ALL leukemia. We have examined a cohort of 110 cases of ALL to determine the cytogenetic profiles and prevalence of FLT3 mutations and analysis of the more frequently observed abnormalities and its correlations to other biologic factors and patient outcomes and to compare our results with previously published results...
2017: Clinical Medicine Insights. Oncology
https://www.readbyqxmd.com/read/28809761/the-t-12-21-p13-q22-in-pediatric-b-acute-lymphoblastic-leukemia-an-update
#2
Maximilian Becker, Kristie Liu, Carlos A Tirado
Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is the most common hematological malignancy in children, and the t(12;21)(p13;q22) occurs in approximately 25% of these cases, making it is the most prevalent chromosomal abnormality. The t(12;21) which disrupts hematopoietic differentiation and proliferation, and can be present as a sole abnormality or within the context of a complex karyotype characterized by three or more chromosomal abnormalities. The prognosis of t(12;21) within a complex karyotype is extensively debated...
2017: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/28808226/atr-inhibition-facilitates-targeting-of-leukemia-dependence-on-convergent-nucleotide-biosynthetic-pathways
#3
Thuc M Le, Soumya Poddar, Joseph R Capri, Evan R Abt, Woosuk Kim, Liu Wei, Nhu T Uong, Chloe M Cheng, Daniel Braas, Mina Nikanjam, Peter Rix, Daria Merkurjev, Jesse Zaretsky, Harley I Kornblum, Antoni Ribas, Harvey R Herschman, Julian Whitelegge, Kym F Faull, Timothy R Donahue, Johannes Czernin, Caius G Radu
Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the activity of their respective rate-limiting enzymes, ribonucleotide reductase (RNR) and deoxycytidine kinase (dCK), via distinct molecular mechanisms...
August 14, 2017: Nature Communications
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/28790849/immunotargeting-relapsed-or-refractory-precursor-b-cell-acute-lymphoblastic-leukemia-role-of-blinatumomab
#6
REVIEW
Manon Queudeville, Rupert Handgretinger, Martin Ebinger
Patients with refractory or relapsed (R/R) acute lymphoblastic leukemia (ALL) have a dismal prognosis of around 5% long-term survival when treated with cytotoxic chemotherapy and allogenic stem cell transplantation. T-cell immunobased strategies open up new therapeutic perspectives. Blinatumomab is the first of a new class of antibody constructs that was labeled bispecific T-cell engager (BiTE): it consists of two single chain variable fragment connected with a flexible linker, one side binding CD3, the other CD19...
2017: OncoTargets and Therapy
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/28790105/value-of-cytogenetic-abnormalities-in-adults-with-ph-negative-b-cell-precursor-acute-lymphoblastic-leukemia
#8
Marina Lafage-Pochitaloff, Laurence Baranger, Mathilde Hunault, Wendy Cuccuini, Christine Lefebvre, Audrey Bidet, Isabelle Tigaud, Virginie Eclache, Eric Delabesse, Chrystèle Bilhou-Nabéra, Christine Terré, Elise Chapiro, Nathalie Gachard, Marie-Joelle Mozziconacci, Geneviève Ameye, Sarah Porter, Nathalie Grardel, Marie C Béné, Yves Chalandon, Carlos Graux, Françoise Huguet, Véronique Lhéritier, Norbert Ifrah, Hervé Dombret
Multiple cytogenetic subgroups have been described in adult Philadelphia chromosome (Ph)-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), often comprising small numbers of patients. In this study, we aimed to reassess the prognostic value of cytogenetic abnormalities in a large series of 617 adult patients with Ph-negative BCP-ALL (median age, 38 years), treated in the intensified GRAALL-2003/2005 trials. Combined data from karyotype, DNA index, FISH and/or PCR screening for relevant abnormalities were centrally reviewed and were informative in 542 cases (88%), allowing classification in ten exclusive primary cytogenetic subgroups and in secondary subgroups including complex and monosomal karyotypes...
August 8, 2017: Blood
https://www.readbyqxmd.com/read/28777460/phosphatidylinositol-3-kinase-inhibition-potentiates-glucocorticoid-response-in-b-cell-acute-lymphoblastic-leukemia
#9
Cecilia Evangelisti, Alessandra Cappellini, Mariana Oliveira, Rita Fragoso, João T Barata, Alice Bertaina, Franco Locatelli, Carolina Simioni, Luca M Neri, Francesca Chiarini, Annalisa Lonetti, Francesca Buontempo, Ester Orsini, Andrea Pession, Lucia Manzoli, Alberto Maria Martelli, Camilla Evangelisti
Despite remarkable progress in polychemotherapy protocols, pediatric B-cell acute lymphoblastic leukemia (B-ALL) remains fatal in around 20% of cases. Hence, novel targeted therapies are needed for patients with poor prognosis. Glucocorticoids (GCs) are drugs commonly administrated for B-ALL treatment. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin signaling pathway is frequently observed in B-ALL and contributes to GC-resistance. Here, we analyzed for the first time to our knowledge, the therapeutic potential of pan and isoform-selective PI3K p110 inhibitors, alone or combined with dexamethasone (DEX), in B-ALL leukemia cell lines and patient samples...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28768245/the-af4-mll-fusion-transiently-augments-multilineage-hematopoietic-engraftment-but-is-not-sufficient-to-initiate-leukemia-in-cord-blood-cd34-cells
#10
Cristina Prieto, Rolf Marschalek, Alessa Kühn, Adelheid Bursen, Clara Bueno, Pablo Menéndez
The translocation t(4;11)(q21;q23) is the hallmark genetic abnormality associated with infant pro-B acute lymphoblastic leukemia (B-ALL) and has the highest frequency of rearrangement in Mixed-lineage leukemia (MLL) leukemias. Unlike other MLL translocations, MLL-AF4-induced proB-ALL is exceptionally difficult to model in mice/humans. Previous work has investigated the relevance of the reciprocal translocation fusion protein AF4-MLL for t(4;11) leukemia, finding that AF4-MLL is capable of inducing proB-ALL without requirement for MLL-AF4 when expressed in murine hematopoietic stem/progenitor cells (HSPCs)...
July 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28766535/-adult-b-cell-acute-lymphoblastic-leukemias-conclusions-of-the-russian-prospective-multicenter-study-all-2009
#11
E N Parovichnikova, V V Troitskaya, A N Sokolov, S N Bondarenko, O A Gavrilina, G A Baskhaeva, B V Biderman, I A Lukyanova, L A Kuz'mina, G A Klyasova, S K Kravchenko, E O Gribanova, E E Zvonkov, Z Kh Akhmerzaeva, O Yu Baranova, T S Kaporskaya, T V Ryltsova, E N Zotina, E E Zinina, O S Samoilova, K D Kaplanov, L V Gavrilova, T S Konstantinova, V A Lapin, A S Pristupa, A S Eluferyeva, T N Obukhova, I S Piskunova, I V Gal'tseva, V N Dvirnyk, M A Rusinov, S M Kulikov, V G Savchenko
AIM: To analyze the efficiency and reproducibility of the ALL-2009 protocol within the Russian prospective multicenter study based on different principles of cytostatic effects (non-intensive, but continuous cytotoxic treatment and a small number of allogeneic hematopoietic stem cells). SUBJECTS AND METHODS: The ALL-2009 (NCT01193933) study conducted in April 2009 to December 2016 included 194 patients (95 males and 99 females) aged 15 to 55 years (median age 28 years) with Ph-negative B-cell acute lymphoblastic leukemia (ALL)...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28760688/the-oligodendrocyte-lineage-transcription-factor-2-olig2-is-epigenetically-regulated-in-acute-myeloid-leukemia
#12
Arzu Yalcin, Marlon Kovarbasic, Julius Wehrle, Rainer Claus, Heiko Becker, Mahmoud Abdelkarim, Verena I Gaidzik, Andrea Schmidts, Ralph Wäsch, Heike L Pahl, Konstanze Döhner, Lars Bullinger, Justus Duyster, Michael Lübbert, Björn Hackanson
DNA methylation differences between normal and cancer tissue resulting in differential expression of genes are a hallmark of acute myeloid leukemia (AML) and can provide growth advantage for malignant cells via silencing of specific genes, e.g. transcription factors. The oligodendrocyte lineage transcription factor 2 (OLIG2) was reported to be differentially methylated and associated with prognosis in AML and - as demonstrated for acute lymphoblastic leukemia and malignant glioma - may play a role in malignant transformation...
July 28, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28760298/minimal-residual-disease-assessment-and-risk-based-therapy-in-acute-lymphoblastic-leukemia
#13
REVIEW
Renato Bassan, Tamara Intermesoli, Annamaria Scattolin, Piera Viero, Elena Maino, Rosaria Sancetta, Francesca Carobolante, Francesca Gianni, Paola Stefanoni, Manuela Tosi, Orietta Spinelli, Alessandro Rambaldi
The study of minimal residual disease (MRD) in adult patients with acute lymphoblastic leukemia (ALL) allows a greater refinement of the individual risk classification and is the best support for risk-specific therapy with or without allogeneic hematopoietic cell transplantation (HCT). Using case-specific sensitive molecular probes or multiparametric flow cytometry on marrow samples obtained from the end of induction until midconsolidation, MRD assays can detect up to 1 leukemic cell of 10,000 total mononuclear cells (sensitivity, 0...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28756350/immunotherapy-in-adult-acute-leukemia
#14
REVIEW
Sabine Blum, Filipe Martins, Michael Lübbert
The treatment of acute myeloid leukemia (AML) did not evolve profoundly in the last decades. Some improvement has been made for acute lymphoblastic leukemia (ALL). Emerging new treatment modalities, such as immunotherapy, are now beginning to be available for acute leukemia, mostly for patients suffering from ALL. This review aims to give an overview of these new therapeutic approaches, especially those already available. The focus is on cell-based immunotherapy, or molecules using preexisting host cells. Underlying mechanisms are explained and an overview of clinical experience with phase 1-3 studies is given...
June 29, 2017: Leukemia Research
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
#15
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
#16
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/28751490/panel-oks-car-t-therapy-for-leukemia
#17
(no author information available yet)
An expert panel recommended approval of Novartis's experimental chimeric antigen T-cell therapy, tisagenlecleucel, for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia. The therapy would be the first of its kind approved for cancer and has the potential to transform standard of care for advanced blood cancers.
July 27, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28748759/targeting-kinase-activating-genetic-lesions-to-improve-therapy-of-pediatric-acute-lymphoblastic-leukemia
#18
Franca Raffaella, Natasa Karas Kuzelicki, Claudio Sorio, Eleonora Toffoletti, Oksana Montecchini, Alice Poropat, Marco Rabusin, Debora Curci, Dino Paladin, Gabriele Stocco, Giuliana Decorti
Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children, characterized by an abnormal proliferation of immature lymphoid cells. Thanks to risk-adapted combination chemotherapy treatments currently used, survival at 5 years has reached 90%. ALL is a heterogeneous disease from a genetic point of view: patients' lymphoblasts may harbor in fact several chromosomal alterations, some of which have prognostic and therapeutic value. Of particular importance is the translocation t(9;22)(q34;q11...
July 27, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28747286/coexistence-of-ezh2-notch1-il7r-and-phf6-mutations-in-adult-t-cell-acute-lymphoblastic-leukemia
#19
Xilian Zhou, Yan Gu, Qi Han, Mario Soliman, Chunhua Song, Zheng Ge
No abstract text is available yet for this article.
July 27, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28744141/the-translational-expression-of-abca2-and-abca3-is-a-strong-prognostic-biomarker-for-multidrug-resistance-in-pediatric-acute-lymphoblastic-leukemia
#20
Narges Aberuyi, Soheila Rahgozar, Zohreh Khosravi Dehaghi, Alireza Moafi, Andrea Masotti, Alessandro Paolini
PURPOSE: The aim of this work was to study the correlation between the expressions of the ABCA2 and ABCA3 genes at the mRNA and protein levels in children with acute lymphoblastic leukemia (ALL) and the effects of this association on multidrug resistance (MDR). MATERIALS AND METHODS: Sixty-nine children with de novo ALL and 25 controls were enrolled in the study. Mononuclear cells were isolated from the bone marrow. The mRNA levels of ABCA2 and ABCA3 were measured by real-time polymerase chain reaction (PCR)...
2017: OncoTargets and Therapy
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