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https://www.readbyqxmd.com/read/29342275/hot-spot-kif5a-mutations-cause-familial-als
#1
David Brenner, Rüstem Yilmaz, Kathrin Müller, Torsten Grehl, Susanne Petri, Thomas Meyer, Julian Grosskreutz, Patrick Weydt, Wolfgang Ruf, Christoph Neuwirth, Markus Weber, Susana Pinto, Kristl G Claeys, Berthold Schrank, Berit Jordan, Antje Knehr, Kornelia Günther, Annemarie Hübers, Daniel Zeller, Christian Kubisch, Sibylle Jablonka, Michael Sendtner, Thomas Klopstock, Mamede de Carvalho, Anne Sperfeld, Guntram Borck, Alexander E Volk, Johannes Dorst, Joachim Weis, Markus Otto, Joachim Schuster, Kelly Del Tredici, Heiko Braak, Karin M Danzer, Axel Freischmidt, Thomas Meitinger, Tim M Strom, Albert C Ludolph, Peter M Andersen, Jochen H Weishaupt
Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis...
January 12, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29342136/clonal-evolution-mechanisms-in-nt5c2-mutant-relapsed-acute-lymphoblastic-leukaemia
#2
Gannie Tzoneva, Chelsea L Dieck, Koichi Oshima, Alberto Ambesi-Impiombato, Marta Sánchez-Martín, Chioma J Madubata, Hossein Khiabanian, Jiangyan Yu, Esme Waanders, Ilaria Iacobucci, Maria Luisa Sulis, Motohiro Kato, Katsuyoshi Koh, Maddalena Paganin, Giuseppe Basso, Julie M Gastier-Foster, Mignon L Loh, Renate Kirschner-Schwabe, Charles G Mullighan, Raul Rabadan, Adolfo A Ferrando
Relapsed acute lymphoblastic leukaemia (ALL) is associated with resistance to chemotherapy and poor prognosis. Gain-of-function mutations in the 5'-nucleotidase, cytosolic II (NT5C2) gene induce resistance to 6-mercaptopurine and are selectively present in relapsed ALL. Yet, the mechanisms involved in NT5C2 mutation-driven clonal evolution during the initiation of leukaemia, disease progression and relapse remain unknown. Here we use a conditional-and-inducible leukaemia model to demonstrate that expression of NT5C2(R367Q), a highly prevalent relapsed-ALL NT5C2 mutation, induces resistance to chemotherapy with 6-mercaptopurine at the cost of impaired leukaemia cell growth and leukaemia-initiating cell activity...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29339403/a-phase-1-study-of-azacitidine-combined-with-chemotherapy-in-childhood-leukemia-a-report-from-tacl-consortium
#3
Weili Sun, Timothy Triche, Jemily Malvar, Paul Gaynon, Richard Sposto, Xiaojing Yang, Henrique Bittencourt, Andrew E Place, Yoav Messinger, Chris Fraser, Luciano Dalla-Pozza, Bodour Salhia, Peter Jones, Alan S Wayne, Lia Gore, Todd M Cooper, Gangning Liang
Growing evidence indicates that aberrant DNA hypermethylation is associated with leukemogenesis, chemotherapy resistance, and relapse. DNA methyltransferase inhibitors such as azacitidine and decitabine have been shown to reverse drug resistance and prime leukemia cells to cytotoxic agents in vitro. Here we report the first pediatric phase 1 study using azacitidine in sequence with chemotherapy in patients with relapsed/refractory leukemia. Fourteen patients were enrolled, twelve with acute myeloid leukemia (AML) and two with acute lymphoblastic leukemia (ALL)...
January 16, 2018: Blood
https://www.readbyqxmd.com/read/29338593/expression-and-role-of-granulocyte-macrophage-colony-stimulating-factor-receptor-gm-csfr-and-granulocyte-colony-stimulating-factor-receptor-g-csfr-on-ph-positive-acute-b-lymphoblastic-leukemia
#4
Yong Wu, Ming Tan, Mei-Ling Chen, Yuan-Zhong Chen
OBJECTIVE: We observed that ph + ALL patients administrated with recombinant human G-CSF (rhG-CSF) after intense chemotherapy have presented a trend of disease relapse. Thus, we aim to thoroughly investigate the expression and role of GM-CSFR and G-CSFR on ph + ALL patients. METHOD: SUP-B15, BALL-1 and primary leukemia cells were used in this study. Transcript levels were analyzed by quantitative PCR while cell viability was measured using a CCK-8 assay...
January 17, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29338345/effect-of-anacardium-occidentale-leaf-extract-on-human-acute-lymphoblastic-leukaemia-cell-lines
#5
Janaína M Santos, Nathalia M Cury, José A Yunes, Jorge A López, Maria L Hernández-Macedo
Anacardium occidentale leaves are used in folk medicine due its therapeutic properties attributed to phenolic compounds. Therefore, this study was undertaken on its hydroethanolic leaf extract (AoHE) to evaluate cytotoxicity and apoptosis induction on acute lymphoblastic leukaemia cells. Results indicated that AoHE interfered in the cell cycle progression, inducing apoptosis by activation of casp3 at lower concentrations, thence, a promising candidate for the development of new cancer drugs.
January 16, 2018: Natural Product Research
https://www.readbyqxmd.com/read/29337223/sequential-conditioning-with-thiotepa-in-t-cell-replete-hematopoietic-stem-cell-transplantation-for-the-treatment-of-refractory-hematological-malignancies-comparison-with-matched-related-haplo-mismatched-and-unrelated-donors
#6
Rémy Duléry, Anne-Lise Ménard, Sylvain Chantepie, Jean El Cheikh, Sylvie François, Jérémy Delage, Federica Giannotti, Annalisa Ruggeri, Eolia Brissot, Giorgia Battipaglia, Florent Malard, Ramdane Belhocine, Simona Sestili, Anne Vekhoff, François Delhommeau, Oumédaly Reman, Ollivier Legrand, Myriam Labopin, Marie-Thérèse Rubio, Mohamad Mohty
The results of conventional allogeneic stem cell transplantation (SCT) in refractory hematological malignancies are poor. Sequential strategies have shown promising results in refractory acute myeloid leukemia (AML), but have not been validated in a haploidentical (Haplo) setting. We developed a new sequential approach combining chemotherapy with broad anti-tumor activity (thiotepa 10 mg/kg, etoposide 400 mg/m2, cyclophosphamide 1600 mg/m2 from Day-15 to -10), followed after 3 days of rest by reduced-intensity conditioning regimen (fludarabine 150 mg/m2, intravenous busulfan 6...
January 11, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29336635/lymphomatoid-granulomatosis-in-a-14-year-old-boy-with-trisomy-21-and-history-of-b-lymphoblastic-leukemia-lymphoma
#7
Anna Paulina Matynia, Sherrie L Perkins, David Li
BACKGROUND: Lymphomatoid granulomatosis is a EBV-driven lymphoproliferative disorder that has been reported in association with immunodeficiency, but only exceptionally in patients with hematopoietic malignancy. CASE REPORT: A 14-year-old boy with trisomy-21 and a history of B-lymphoblastic leukemia/lymphoma (B-ALL) diagnosed 1.5 years prior, on maintenance chemotherapy, presented with fever and respiratory symptoms. Chest X-ray revealed right-lower-lobe consolidation...
January 16, 2018: Fetal and Pediatric Pathology
https://www.readbyqxmd.com/read/29335768/ctla-4-polymorphisms-influence-on-transplant-related-mortality-and-survival-in-children-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#8
Judith Hammrich, Susan Wittig, Thomas Ernst, Bernd Gruhn
PURPOSE: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative approach for a variety of hematological diseases; however, it is still associated with substantial morbidity and mortality. Transplant-related mortality (TRM) after HSCT depends mainly on the toxicity of the conditioning regimen, infections, and graft-versus-host disease. The purpose of this study was to identify the association between CTLA-4 single nucleotide polymorphisms and TRM in children undergoing allogeneic HSCT...
January 15, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29335448/regional-evaluation-of-childhood-acute-lymphoblastic-leukemia-genetic-susceptibility-loci-among-japanese
#9
Kevin Y Urayama, Masatoshi Takagi, Takahisa Kawaguchi, Keitaro Matsuo, Yoichi Tanaka, Yoko Ayukawa, Yuki Arakawa, Daisuke Hasegawa, Yuki Yuza, Takashi Kaneko, Yasushi Noguchi, Yuichi Taneyama, Setsuo Ota, Takeshi Inukai, Masakatsu Yanagimachi, Dai Keino, Kazutoshi Koike, Daisuke Toyama, Yozo Nakazawa, Hidemitsu Kurosawa, Kozue Nakamura, Koichi Moriwaki, Hiroaki Goto, Yujin Sekinaka, Daisuke Morita, Motohiro Kato, Junko Takita, Toshihiro Tanaka, Johji Inazawa, Katsuyoshi Koh, Yasushi Ishida, Akira Ohara, Shuki Mizutani, Fumihiko Matsuda, Atsushi Manabe
Genome-wide association studies (GWAS) performed mostly in populations of European and Hispanic ancestry have confirmed an inherited genetic basis for childhood acute lymphoblastic leukemia (ALL), but these associations are less clear in other races/ethnicities. DNA samples from ALL patients (aged 0-19 years) previously enrolled onto a Tokyo Children's Cancer Study Group trial were collected during 2013-2015, and underwent single nucleotide polymorphism (SNP) microarray genotyping resulting in 527 B-cell ALL for analysis...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29334537/isolated-central-nervous-system-chloroma-as-a-presenting-sign-of-relapsed-pediatric-acute-lymphoblastic-leukemia
#10
Jessica L Heath, Waitman K Aumann, Charles M Maxfield, Daniel S Wechsler
Central nervous system (CNS) chloromas are an exceedingly rare presentation of CNS relapse in acute lymphoblastic leukemia (ALL). We report a relapsed ALL patient who presented with 2 separate chloromas and cerebrospinal fluid lymphoblastocytosis, and outline a treatment plan of systemic chemotherapy and CNS-directed radiation therapy. A review of the literature indicates that multiagent chemotherapy combined with CNS radiotherapy is effective, with hematopoietic stem cell transplantation used in half of reported cases...
January 12, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29334534/symptomatic-hyperammonemia-with-erwinia-chrysanthemi-derived-asparaginase-in-pediatric-leukemia-patients
#11
Nathan Gossai, Michael Richards, Lara Boman, Yoav Messinger, Sara Gernbacher, Joanna Perkins, Bruce Bostrom
Erwinia chrysanthemi-derived asparaginase is increasingly integral to acute lymphoblastic leukemia therapy. In our series, 16% of patients developed symptomatic hyperammonemia following Erwinia administration with symptoms including refractory nausea, vomiting, profound fatigue, malaise, and coma. This series of patients receiving Erwinia indicates higher than expected incidence of hyperammonemia, correlation between ammonia and asparaginase levels and therapeutic asparaginase activity levels despite dose reduction...
January 12, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29334255/ngs-based-methylation-profiling-differentiates-tcf3-hlf-and-tcf3-pbx1-positive-b-cell-acute-lymphoblastic-leukemia
#12
Priyadarshini Kachroo, Silke Szymczak, Femke-Anouska Heinsen, Michael Forster, Jörn Bethune, Georg Hemmrich-Stanisak, Lewis Baker, Martin Schrappe, Martin Stanulla, Andre Franke
AIM: To determine whether methylation differences between mostly fatal TCF3-HLF and curable TCF3-PBX1 pediatric acute lymphoblastic leukemia subtypes can be associated with differential gene expression and remission. MATERIALS & METHODS: Five (extremely rare) TCF3-HLF versus five (very similar) TCF3-PBX1 patients were sampled before and after remission and analyzed using reduced representation bisulfite sequencing and RNA-sequencing. RESULTS: We identified 7000 differentially methylated CpG sites between subtypes, of which 78% had lower methylation levels in TCF3-HLF...
January 15, 2018: Epigenomics
https://www.readbyqxmd.com/read/29334169/impact-of-baseline-clinical-and-laboratory-features-on-the-risk-of-thrombosis-in-children-with-acute-lymphoblastic-leukemia-a-prospective-evaluation
#13
Uma H Athale, T Mizrahi, C Laverdière, T Nayiager, Y-L Delva, G Foster, L Thabane, M David, J-M Leclerc, A K C Chan
BACKGROUND: Children with acute lymphoblastic leukemia (ALL) have increased risk of thromboembolism (TE). However, the predictors of ALL-associated TE are as yet uncertain. OBJECTIVE: This exploratory, prospective cohort study evaluated the effects of clinical (age, gender, ALL risk group) and laboratory variables (hematological parameters, ABO blood group, inherited and acquired prothrombotic defects [PDs]) at diagnosis on the development of symptomatic TE (sTE) in children (aged 1 to ≤18) treated on the Dana-Farber Cancer Institute ALL 05-001 study...
January 15, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29333397/pseudo-chediak-higashi-inclusions-in-a-case-of-acute-lymphoblastic-leukemia
#14
Sarita Pradhan, Sima Chauhan
No abstract text is available yet for this article.
December 2017: Blood Research
https://www.readbyqxmd.com/read/29333125/association-between-slc19a1-gene-polymorphism-and-high-dose-methotrexate-toxicity-in-childhood-acute-lymphoblastic-leukaemia-and-non-hodgkin-malignant-lymphoma-introducing-a-haplotype-based-approach
#15
Barbara Faganel Kotnik, Janez Jazbec, Petra Bohanec Grabar, Cristina Rodriguez-Antona, Vita Dolzan
Background: We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML). Patients and methods: Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities. Results: Patients with rs2838958 TT genotype had higher probability for mucositis development as compared to carriers of at least one rs2838958 C allele (OR 0...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29333004/drosha-rs642321-polymorphism-influence-susceptibility-to-childhood-acute-lymphoblastic-leukemia-a-preliminary-report
#16
Mohammad Hashemi, Seyed-Shahaboddin Hasani, Majid Naderi
Introduction: It has been well known that the microRNA biogenesis is involved in the pathogenesis of various diseases. We investigated the possible association between DROSHA rs642321 variant and risk of acute lymphocytic leukemia (ALL). Materials and Methods: We genotyped 75 children diagnosed with ALL and 115 age- and sex-matched children with no history of cancer of any type (as the control group) by the tetra amplification refractory mutation system-polymerase chain reaction...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29330417/high-stap1-expression-in-dux4-rearranged-cases-is-not-suitable-as-therapeutic-target-in-pediatric-b-cell-precursor-acute-lymphoblastic-leukemia
#17
Elisabeth M P Steeghs, Marjolein Bakker, Alex Q Hoogkamer, Judith M Boer, Quirine J Hartman, Femke Stalpers, Gabriele Escherich, Valerie de Haas, Hester A de Groot-Kruseman, Rob Pieters, Monique L den Boer
Approximately 25% of the pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cases are genetically unclassified. More thorough elucidation of the pathobiology of these genetically unclassified ('B-other') cases may identify novel treatment options. We analyzed gene expression profiles of 572 pediatric BCP-ALL cases, representing all major ALL subtypes. High expression of STAP1, an adaptor protein downstream of the B-cell receptor (BCR), was identified in BCR-ABL1-like and non-BCR-ABL1-like B-other cases...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330392/haploidentical-hematopoietic-sct-using-helical-tomotherapy-for-total-body-irradiation-and-targeted-dose-boost-in-patients-with-high-risk-refractory-acute-lymphoblastic-leukemia
#18
Zujun Jiang, Junsong Jia, Chunyan Yue, Yan Pang, Zenghui Liu, Ling Ouyang, Hongbo Li, Jinjian Zhang, Ting Wen, Jing Li, Zhiqiang Li, Yan Wang, Yang Xiao, Haowen Xiao
A novel conditioning regimen using helical tomotherapy (HT) was developed to deliver 10 Gy for total body irradiation (TBI) and simultaneously augment dose to 12 Gy for targeted dose boost to total marrow, central nervous system leukemia, and extramedullary disease sites in patients with high-risk or relapsed/refractory acute lymphoblastic leukemia (ALL) receiving haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fourteen patients were included, eight of these patients were in first complete remission (CR1), one was in CR2, one had a partial response and four patients had refractory disease at transplantation...
January 12, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29330284/novel-intergenically-spliced-chimera-nfatc3-pla2g15-is-associated-with-aggressive-t-all-biology-and-outcome
#19
Jonathan Bond, Christine Tran Quang, Guillaume Hypolite, Mohamed Belhocine, Aurélie Bergon, Gaëlle Cordonnier, Jacques Ghysdael, Elizabeth Macintyre, Nicolas Boissel, Salvatore Spicuglia, Vahid Asnafi
Leukemias are frequently characterized by the expression of oncogenic fusion chimeras that normally arise due to chromosomal rearrangements. Intergenically-spliced chimeric RNAs (ISCs) are transcribed in the absence of structural genomic changes, and aberrant ISC expression is now recognized as a potential driver of cancer. To better understand these potential oncogenic drivers, high-throughput RNA-sequencing (RNA-seq) was performed on T-acute lymphoblastic leukemia (T-ALL) patient specimens (n=24) and candidate T-ALL-related ISCs were identified (n=55; a median of 4 per patient)...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330145/mbd2-ablation-impairs-lymphopoiesis-and-impedes-progression-and-maintenance-of-t-all
#20
Mi Zhou, Kuangguo Zhou, Ling Cheng, Xing Chen, Jue Wang, Xiao-Min Wang, Yingchi Zhang, Qilin Yu, Shu Zhang, Di Wang, Liang Huang, Mei Huang, Ding Ma, Tao Cheng, Cong-Yi Wang, Weiping Yuan, Jianfeng Zhou
Aberrant DNA methylation patterns in leukemia might be exploited for therapeutic targeting. In this study, we employed a genetically deficient mouse model to explore the role of the methylated DNA binding protein MBD2 in normal and malignant hematopoiesis. MBD2 ablation led to diminished lymphocytes. Functional defects of the lymphoid compartment were also observed after in vivo reconstitution of MBD2-deficient hematopoietic stem cells (HSC). In an established model of Notch1-driven T cell acute lymphoblastic leukemia (T-ALL), MBD2 ablation impeded malignant progression and maintenance by attenuating the Wnt signaling pathway...
January 12, 2018: Cancer Research
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