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Pediatric Acute Lymphoblastic Leukemia

Jolanta Skalska-Sadowska, Małgorzata Dawidowska, Bronisława Szarzyńska-Zawadzka, Małgorzata Jarmuż-Szymczak, Joanna Czerwińska-Rybak, Ludomiła Machowska, Katarzyna Derwich
We report a pediatric case of acute T-lymphoblastic leukemia (T-ALL) with NOTCH1(wt) , FBXW7(wt) , STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and a minor t(8;14)(q24;q11)-positive subclone. Undetectable by a flow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by fluorescence in situ hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set of remaining molecular alterations...
October 19, 2016: Pediatric Blood & Cancer
Jinghua Wu, Shan Jia, Changxi Wang, Wei Zhang, Sixi Liu, Xiaojing Zeng, Huirong Mai, Xiuli Yuan, Yuanping Du, Xiaodong Wang, Xueyu Hong, Xuemei Li, Feiqiu Wen, Xun Xu, Jianhua Pan, Changgang Li, Xiao Liu
Acute B lymphoblastic leukemia (B-ALL) is one of the most common types of childhood cancer worldwide and chemotherapy is the main treatment approach. Despite good response rates to chemotherapy regiments, many patients eventually relapse and minimal residual disease (MRD) is the leading risk factor for relapse. The evolution of leukemic clones during disease development and treatment may have clinical significance. In this study, we performed immunoglobulin heavy chain (IGH) repertoire high throughput sequencing (HTS) on the diagnostic and post-treatment samples of 51 pediatric B-ALL patients...
2016: Frontiers in Immunology
Marcin Braun, Agata Pastorczak, Wojciech Fendler, Joanna Madzio, Bartlomiej Tomasik, Joanna Taha, Marta Bielska, Lukasz Sedek, Tomasz Szczepanski, Michal Matysiak, Katarzyna Derwich, Monika Lejman, Jerzy Kowalczyk, Bernarda Kazanowska, Wanda Badowska, Jan Styczynski, Nina Irga-Jaworska, Joanna Trelinska, Beata Zalewska-Szewczyk, Filip Pierlejewski, Iwona Wlodarska, Wojciech Młynarski
The inactivation of tumor suppressor genes located within 9p21 locus (CDKN2A, CDKN2B) occurs in up to 30% of children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but its independent prognostic significance remains controversial. In order to investigate the prognostic impact of deletions and promoter methylation within 9p21, 641 children with newly diagnosed BCP-ALL using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) were investigated. A total of 169 (26.4%) microdeletions in 9p21 were detected, of which 71 were homozygous...
October 18, 2016: Leukemia & Lymphoma
E Waanders, B Scheijen, M C J Jongmans, H Venselaar, S V van Reijmersdal, A H A van Dijk, A Pastorczak, R D A Weren, C E van der Schoot, M van de Vorst, E Sonneveld, N Hoogerbrugge, V H J van der Velden, B Gruhn, P M Hoogerbrugge, J J M van Dongen, A G van Kessel, F N van Leeuwen, R P Kuiper
The contribution of genetic predisposing factors to the development of pediatric acute lymphoblastic leukemia (ALL), the most frequently diagnosed cancer in childhood, has not been fully elucidated. Children presenting with multiple de novo leukemias are more likely to suffer from genetic predisposition. Here, we selected five of these patients and analyzed the mutational spectrum of normal and malignant tissues. In two patients, we identified germline mutations in TYK2, a member of the JAK tyrosine kinase family...
October 13, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Judith Feucht, Simone Kayser, David Gorodezki, Mohamad Hamieh, Michaela Döring, Franziska Blaeschke, Patrick Schlegel, Hans Bösmüller, Leticia Quintanilla-Fend, Martin Ebinger, Peter Lang, Rupert Handgretinger, Tobias Feuchtinger
T-cell immunotherapies are promising options in relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We investigated the effect of co-signaling molecules on T-cell attack against leukemia mediated by CD19/CD3-bispecific T-cell engager. Primary CD19+ ALL blasts (n≥10) and physiologic CD19+CD10+ bone marrow precursors were screened for 20 co-signaling molecules. PD-L1, PD-1, LAG-3, CD40, CD86, CD27, CD70 and HVEM revealed different stimulatory and inhibitory profiles of pediatric ALL compared to physiologic cells, with PD-L1 and CD86 as most prominent inhibitory and stimulatory markers...
September 30, 2016: Oncotarget
M Kato, S Ishimaru, M Seki, K Yoshida, Y Shiraishi, K Chiba, N Kakiuchi, Y Sato, H Ueno, H Tanaka, T Inukai, D Tomizawa, D Hasegawa, T Osumi, Y Arakawa, T Aoki, M Okuya, K Kaizu, K Kato, Y Taneyama, H Goto, T Taki, M Takagi, M Sanada, K Koh, J Takita, S Miyano, S Ogawa, A Ohara, M Tsuchida, A Manabe
In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which maintenance therapy was terminated at one year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information which had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear...
October 4, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Meng-Ju Li, Hsi-Che Liu, Hsiu-Ju Yen, Tang-Her Jaing, Dong-Tsamn Lin, Chao-Ping Yang, Kai-Hsin Lin, Iou-Jih Hung, Shiann-Tarng Jou, Meng-Yao Lu, Chih-Cheng Hsiao, Ching-Tien Peng, Tai-Tsung Chang, Shih-Chung Wang, Ming-Tsan Lin, Jiann-Shiuh Chen, Te-Kau Chang, Giun-Yi Hung, Kang-Hsi Wu, Yung-Li Yang, Hsiu-Hao Chang, Shih-Hsiang Chen, Ting-Chi Yeh, Chao-Neng Cheng, Pei-Chin Lin, Shyh-Shin Chiou, Jiunn-Ming Sheen, Shin-Nan Cheng, Shu-Huey Chen, Yu-Hsiang Chang, Wan-Ling Ho, Yu-Hua Chao, Rong-Long Chen, Bow-Wen Chen, Jinn-Li Wang, Yuh-Lin Hsieh, Yu-Mei Liao, Shang-Hsien Yang, Wan-Hui Chang, Yu-Mei Y Chao, Der-Cherng Liang
BACKGROUND: Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard-risk (SR, or "low-risk" in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy. PROCEDURE: From 2002 to 2012, all newly diagnosed children with ALL in Taiwan were enrolled in Taiwan Pediatric Oncology Group ALL-2002 protocol...
October 3, 2016: Pediatric Blood & Cancer
Youssef M Mosaad, Rasha Elashery, Ahmad Darwish, Omar A Sharaf Eldein, Tarek Barakat, Samy Marouf, Noha T Abou El-Khier, Laila F Youssef, Iman M Fawzy
To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = ...
August 9, 2016: Leukemia & Lymphoma
Federico G Antillón, Jessica G Blanco, Patricia D Valverde, Mauricio Castellanos, Claudia P Garrido, Veronica Girón, Tomas R Letona, Emilia J Osorio, Dyna A Borrayo, Ricardo A Mack, Mario A Melgar, Rodolfo Lorenzana, Raul C Ribeiro, Monika Metzger, Valentino Conter, Emanuela Rossi, Maria Grazia Valsecchi
BACKGROUND: The National Pediatric Oncology Unit (UNOP) is the only pediatric hemato-oncology center in Guatemala. METHODS: Patients ages 1 to 17 years with acute lymphoblastic leukemia (ALL) were treated according to modified ALL Intercontinental Berlin-Frankfurt-Münster (IC-BFM) 2002 protocol. Risk classification was based on age, white blood cell count, immunophenotype, genetics (when available), and early response to therapy. RESULTS: From July 2007 to June 2014, 787 patients were treated, including 160 who had standard-risk ALL, 450 who had intermediate-risk ALL, and 177 who had high-risk ALL...
September 28, 2016: Cancer
M Kassick, P P Koffer, T J Kinsella
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Silky Jain, Sandeep Jain, Gauri Kapoor, Anju Virmani, Ram Bajpai
BACKGROUND: Acute lymphoblastic leukemia (ALL) and its treatment are often implicated in adversely affecting bone health. Conflicting reports in the literature and a paucity of studies from the developing world prompted us to study bone mineral density (BMD) in childhood ALL survivors. METHODS: BMD lumbar spine (LS) and whole body (WB) were evaluated, using dual energy x-ray absorptiometry in 65 pediatric ALL survivors who had been off-therapy for at least 2 years...
September 26, 2016: Pediatric Blood & Cancer
Krishnan N Subrahmanian, Young H Shim, Mona D Shah, Brandon H Tran, Alexandra M Stevens, Andrea T Cruz
Emergency departments (EDs) are alert to the possibility of stroke and the need for early interventions to improve long-term clinical outcomes. However, new-onset hemiparesis in pediatric patients with leukemia may be due to a number of different etiologies, including most common side effects from chemotherapeutic agents. We present a case of a 15-year-old boy with pre-B acute lymphoblastic leukemia on chemotherapy, having recently received a high-dose methotrexate infusion in addition to intrathecal methotrexate therapy, who presented to our ED with acute right-sided hemiparesis...
September 23, 2016: Pediatric Emergency Care
Aurelia B Fu, Erica I Hodgman, Lorraine S Burkhalter, Rachel Renkes, Tamra Slone, Adam C Alder
BACKGROUND: Central venous access devices (CVADs) play an important role in the management of pediatric oncology patients; unfortunately, they are also associated with potentially serious complication rates. We hypothesized that, despite the significantly different disease courses typical of acute lymphoblastic leukemia and acute myelogenous leukemia, there would be identifiable risk factors for premature CVAD removal. METHODS: We retrospectively studied clinical characteristics and procedure records for all patients admitted with a leukemia diagnosis at our institution from May 2009 to July 2014...
October 2016: Journal of Surgical Research
Victoria J Forster, Frederik W van Delft, Susan F Baird, Shona Mair, Roderick Skinner, Christina Halsey
PURPOSE: Methotrexate administration is associated with frequent adverse neurological events during treatment for childhood acute lymphoblastic leukemia. Here, we present evidence to support the role of common drug interactions and low vitamin B12 levels in potentiating methotrexate neurotoxicity. METHODS: We review the published evidence and highlight key potential drug interactions as well as present clinical evidence of severe methotrexate neurotoxicity in conjunction with nitrous oxide anesthesia and measurements of vitamin B12 levels among pediatric leukemia patients during therapy...
September 22, 2016: Cancer Chemotherapy and Pharmacology
Farzaneh Ghazavi, Barbara De Moerloose, Wouter Van Loocke, Annelynn Wallaert, Hetty H Helsmoortel, Alina Ferster, Marleen Bakkus, Geneviève Plat, Eric Delabesse, Anne Uyttebroeck, Filip Van Nieuwerburgh, Dieter Deforce, Nadine Van Roy, Frank Speleman, Yves Benoit, Tim Lammens, Pieter Van Vlierberghe
Overwhelming evidence indicates that long non-coding RNAs have essential roles in tumorigenesis. Nevertheless, their role in the molecular pathogenesis of pediatric B-cell precursor acute lymphoblastic leukemia has not been extensively explored. Here, we conducted a comprehensive analysis of the long non-coding RNA transcriptome in ETV6/RUNX1-positive BCP-ALL, one of the most frequent subtypes of pediatric leukemia. First, we used primary leukemia patient samples to identify an ETV6/RUNX1 specific expression signature consisting of 596 lncRNA transcripts...
September 16, 2016: Oncotarget
Leire Iparraguirre, Angela Gutierrez-Camino, Maitane Umerez, Idoia Martin-Guerrero, Itziar Astigarraga, Aurora Navajas, Ana Sastre, Nagore Garcia de Andoin, Africa Garcia-Orad
OBJECTIVES: Methotrexate (MTX), the key drug in childhood B-cell acute lymphoblastic leukemia (B-ALL) therapy, often causes toxicity. An association between genetic variants in MTX transport genes and toxicity has been found. It is known that these transporters are regulated by microRNAs (miRNAs), and miRNA single nucleotide polymorphisms (SNPs) interfere with miRNA levels or function. With regard to B-cell ALL, we have previously found rs56103835 in miR-323b that targets ABCC4 associated with MTX plasma levels...
November 2016: Pharmacogenetics and Genomics
Thanh Nha Uyen, Kazuo Sakashita, Lika'a Fasih Y Al-Kzayer, Yozo Nakazawa, Takashi Kurata, Kenichi Koike
BACKGROUND: The outcome of approximately 20% of patients with acute lymphoblastic leukemia (ALL) remains poor because of disease recurrence. We examined whether DNA methylation of cadherin superfamily genes is a useful biomarker for ALL relapse. PROCEDURE: We used Infinium Methylation 450K Arrays to assess genome-wide DNA methylation status. The methylation status of each individual gene was then determined by a combination of bisulfite restriction analysis and genome bisulfite sequencing...
September 19, 2016: Pediatric Blood & Cancer
Kristina Karrman, Bertil Johansson
The most common pediatric malignancy is acute lymphoblastic leukemia (ALL), of which T-cell ALL (T-ALL) comprises 10-15% of cases. T-ALL arises in the thymus from an immature thymocyte as a consequence of a stepwise accumulation of genetic and epigenetic aberrations. Crucial biological processes such as differentiation, self-renewal capacity, proliferation, and apoptosis are targeted and deranged by several types of neoplasia-associated genetic alteration, for example translocations, deletions, and mutations of genes that code for proteins involved in signaling transduction, epigenetic regulation, and transcription...
September 16, 2016: Genes, Chromosomes & Cancer
Troy Z Horvat, Joshua J Pecoraro, Ryan J Daley, Larry W Buie, Amber C King, Raajit K Rampal, Martin S Tallman, Jae H Park, Dan Douer
Asparaginase administration has become a crucial component of front-line pediatric and pediatric-insipired multi-agent regimens for the treatment of acute lymphoblastic leukemia (ALL). The aim of this retrospective study was to assess the safety and feasibility of switching to Erwinia asparaginase after pegaspargase intolerance in adult ALL patients treated at Memorial Sloan Kettering Cancer Center. Our analysis included 10 patients, with a median age of 39 years (range 20-72), male predominance (90%), and a typical B-cell to T-cell ratio (70:30%) for ALL...
August 26, 2016: Leukemia Research
Babasaheb D Yadav, Amy L Samuels, Julia E Wells, Rosemary Sutton, Nicola C Venn, Katerina Bendak, Denise Anderson, Glenn M Marshall, Catherine H Cole, Alex H Beesley, Ursula R Kees, Richard B Lock
Relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem and is thought to be associated with clonal selection during treatment. In this study we used an established pre-clinical model of induction therapy to increase our understanding of the effect of engraftment and chemotherapy on clonal selection and acquisition of drug resistance in vivo. Immune-deficient mice were engrafted with patient diagnostic specimens and exposed to a repeated combination therapy consisting of vincristine, dexamethasone, L-asparaginase and daunorubicin...
August 11, 2016: Oncotarget
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