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Paediatric acute leukaemia

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https://www.readbyqxmd.com/read/28299660/etv6-runx1-acute-lymphoblastic-leukaemia-in-identical-twins
#1
Anthony M Ford, Mel Greaves
Acute leukaemia is the major subtype of paediatric cancer with a cumulative risk of 1 in 2000 for children up to the age of 15 years. Childhood acute lymphoblastic leukaemia (ALL) is a biologically and clinically diverse disease with distinctive subtypes; multiple chromosomal translocations exist within the subtypes and each carries its own prognostic relevance. The most common chromosome translocation observed is the t(12;21) that results in an in-frame fusion between the first five exons of ETV6 (TEL) and almost the entire coding region of RUNX1 (AML1)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28283471/unilateral-facial-nerve-palsy-as-an-early-presenting-symptom-of-relapse-in-a-paediatric-patient-with-acute-lymphoblastic-leukaemia
#2
Leslie Y Chiang, John Ross Crawford, Dennis John Kuo
No abstract text is available yet for this article.
March 10, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28256501/genetic-and-regulatory-mechanism-of-susceptibility-to-high-hyperdiploid-acute-lymphoblastic-leukaemia-at-10p21-2
#3
James B Studd, Jayaram Vijayakrishnan, Minjun Yang, Gabriele Migliorini, Kajsa Paulsson, Richard S Houlston
Despite high-hyperdiploid acute lymphoblastic leukaemia (HD-ALL) being the most common subgroup of paediatric ALL, its aetiology remains unknown. Genome-wide association studies have demonstrated association at 10q21.2. Here, we sought to determine how this region influences HD-ALL risk. We impute genotypes across the locus, finding the single nucleotide polymorphism rs7090445 highly associated with HD-ALL (P=1.54 × 10(-38)), and residing in a predicted enhancer element. We show this region physically interacts with the transcription start site of ARID5B, that alleles of rs7090445 have differential enhancer activity and influence RUNX3 binding...
March 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28215040/who-should-receive-a-transplant-for-acute-lymphoblastic-leukaemia
#4
REVIEW
Rishi Dhawan, David I Marks
Allogeneic haematopoietic cell transplantation continues to be an important curative therapy for acute lymphoblastic leukaemia (ALL). Traditionally accepted indications for allografting adult ALL patients need reevaluation in light of outcomes with paediatric-like intensive regimens. Minimal residual disease status and oncogenetics can be used for restratification of standard risk patients. A greater body of data on haematopoietic cell transplantation (HCT) outcomes from haploidentical and cord blood donor sources has been generated in recent years...
February 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28182813/second-malignant-neoplasms-in-childhood-cancer-survivors-treated-in-a-tertiary-paediatric-oncology-centre
#5
Jia Wei Lim, Frances Sh Yeap, Yiong Huak Chan, Allen Ej Yeoh, Thuan Chong Quah, Poh Lin Tan
Introduction: One of the most feared complications of childhood cancer treatment is second malignant neoplasms (SMNs). This study evaluates the incidence, risk factors and outcomes of SMNs in a tertiary paediatric oncology centre in Singapore. Materials and Methods: A retrospective review was conducted on patients diagnosed with childhood cancer under age 21 and treated at the National University Hospital, Singapore, from January 1990 to 15 April 2012. Case records of patients with SMNs were reviewed. Results: We identified 1124 cases of childhood cancers with a median follow-up of 3...
January 2017: Annals of the Academy of Medicine, Singapore
https://www.readbyqxmd.com/read/28139029/vincristine-induced-peripheral-neuropathy-in-survivors-of-childhood-acute-lymphoblastic-leukaemia
#6
Chee Geap Tay, Vanessa Wan Mun Lee, Lai Choo Ong, Khean Jin Goh, Hany Ariffin, Choong Yi Fong
BACKGROUND: Vincristine, an essential component of childhood acute lymphoblastic leukaemia (ALL) therapeutic protocols, is associated with dose-dependent neurotoxicity, but its long-term morbidity in treated children has not been clearly elucidated. The aim of this study is to determine the prevalence of vincristine-induced peripheral neuropathy (VIPN) among Malaysian childhood ALL survivors and its impact on motor function and quality of life. PROCEDURE: Survivors of childhood ALL aged 4-18 years who had completed chemotherapy for 2 years or more were evaluated for VIPN using both the clinical Total Neuropathy Score (cTNS) and nerve conduction studies...
January 31, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27984637/genomic-characterization-of-paediatric-acute-lymphoblastic-leukaemia-an-opportunity-for-precision-medicine-therapeutics
#7
REVIEW
Sarah K Tasian, Stephen P Hunger
Major advances in genetic and epigenetic profiling of acute lymphoblastic leukaemia (ALL) have enhanced the understanding of key biological subsets of de novo and relapsed ALL, which has led to improved risk stratification of patients. These achievements have further defined critical leukaemia-associated pathways and somatic alterations that may be preferentially sensitive to treatment with kinase inhibitors, epigenetic therapy or other novel agents. Therapeutic success in childhood ALL currently relies upon refined risk stratification of patients based on (i) underlying biological and clinical characteristics, and (ii) depth of initial treatment response with appropriate modulation of chemotherapy intensity...
March 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27861730/clinical-utility-of-next-generation-sequencing-based-minimal-residual-disease-in-paediatric-b-cell-acute-lymphoblastic-leukaemia
#8
Yuko Sekiya, Yinyan Xu, Hideki Muramatsu, Yusuke Okuno, Atsushi Narita, Kyogo Suzuki, Xinan Wang, Nozomu Kawashima, Hirotoshi Sakaguchi, Nao Yoshida, Asahito Hama, Yoshiyuki Takahashi, Koji Kato, Seiji Kojima
We assessed the clinical utility of next-generation sequencing (NGS)-based monitoring of minimal residual disease (MRD) in a uniformly treated cohort of 79 patients with paediatric B-cell acute lymphoblastic leukaemia. Bone marrow samples were collected at the time of diagnosis, days 33 and 80, pre- (4-5 months) and post- (24 months) maintenance therapy time points, and at relapse. We identified leukaemia-specific CDR3 sequences in 72 of 79 patients (91%) and detected MRD in 59 of 232 samples. Although MRD was detected in 28 of 55 samples (51%) on day 33, the frequencies of MRD detection decreased to 25% (16/65) at day 80, 19% (11/58) at 4-5 months and 7·4% (4/54) at 24 months...
November 11, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27807957/-the-contribution-of-the-italian-association-of-paediatric-haematology-and-oncology-aieop
#9
Roberto Rondelli, Momcilo Jankovic, Annarosa Soresina, Maria Grazia Valsecchi, Marisa De Rosa, Marina Cuttini, Riccardo Haupt, Maurizio Aricò, Gianni Bisogno, Franco Locatelli, Corrado Magnani, Franco Merletti, Marco Zecca, Andrea Pession
Since 1972, children affected by cancer took advantage from multi-centric diagnostic and therapeutic protocols produced by the Italian Association of paediatric haematology and oncology (AIEOP). At the beginning, these protocols were used in few well-trained centres, later in almost all Italian haemato-oncological centres. The need of a careful monitoring of his own activity induced AIEOP to achieve, in 1989, an Italian hospital- based registry (database Mod.1.01) of malignant tumours diagnosed and treated in the participating centres, with the aim to quantify the number of cases diagnosed and treated in the different centres, the agreement (or not) to official diagnostic- therapeutic protocols, and the extraregional migration...
September 2016: Epidemiologia e Prevenzione
https://www.readbyqxmd.com/read/27807953/-childhood-cancer-epidemiology-and-available-evidence-on-case-clustering
#10
Milena Maule, Benedetto Terracini
This paper introduces a Monograph on childhood cancer clusters addressed to Italian public health workers, paediatricians and paediatric oncologists, and the general public. Two issues have been underlined in most definitions of cancer clusters reported in the literature over the last 30 years. The first is the need for an unbiased methodological approach for the detection and the interpretation of clustering and of individual clusters. The other is the responsibility for scientists and public health workers to unravel suspicious events and to interact with the population in circumstances which may turn out to be false alarms...
September 2016: Epidemiologia e Prevenzione
https://www.readbyqxmd.com/read/27766626/strategies-for-reducing-the-treatment-related-physical-burden-of-childhood-acute-myeloid-leukaemia-a-review
#11
REVIEW
Henrik Hasle, Gertjan J L Kaspers
Over the last four decades the survival of paediatric patients with acute myeloid leukaemia has gradually increased to 70% in high-income countries. The therapy is very intensive and associated with many acute and long-term side effects. The early death rate has been reduced to 1-4%. The acute toxicity is a limiting factor for improving survival in low-income countries. Transplant is associated with more endocrinological late effects while cardiotoxicity is more common after relapse. Reducing the physical costs of therapy without jeopardizing survival may be accomplished by optimal supportive care, less cardiotoxic anthracyclines, less consolidation courses and strict indications for stem cell transplantation...
January 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27766616/genomics-of-primary-chemoresistance-and-remission-induction-failure-in-paediatric-and-adult-acute-myeloid-leukaemia
#12
Fiona C Brown, Paolo Cifani, Esther Drill, Jie He, Eric Still, Shan Zhong, Sohail Balasubramanian, Dean Pavlick, Bahar Yilmazel, Kristina M Knapp, Todd A Alonzo, Soheil Meshinchi, Richard M Stone, Steven M Kornblau, Guido Marcucci, Alan S Gamis, John C Byrd, Mithat Gonen, Ross L Levine, Alex Kentsis
Cure rates of children and adults with acute myeloid leukaemia (AML) remain unsatisfactory partly due to chemotherapy resistance. We investigated the genetic basis of AML in 107 primary cases by sequencing 670 genes mutated in haematological malignancies. SETBP1, ASXL1 and RELN mutations were significantly associated with primary chemoresistance. We identified genomic alterations not previously described in AML, together with distinct genes that were significantly overexpressed in therapy-resistant AML. Defined gene mutations were sufficient to explain primary induction failure in only a minority of cases...
January 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27766614/comment-on-genomics-of-primary-chemoresistance-and-remission-induction-failure-in-paediatric-and-adult-acute-myeloid-leukaemia
#13
EDITORIAL
Jeffrey A Magee
No abstract text is available yet for this article.
January 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27698462/deciphering-kras-and-nras-mutated-clone-dynamics-in-mll-af4-paediatric-leukaemia-by-ultra-deep-sequencing-analysis
#14
Luca Trentin, Silvia Bresolin, Emanuela Giarin, Michela Bardini, Valentina Serafin, Benedetta Accordi, Franco Fais, Claudya Tenca, Paola De Lorenzo, Maria Grazia Valsecchi, Giovanni Cazzaniga, Geertruy Te Kronnie, Giuseppe Basso
To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia...
October 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27688725/impact-of-mtor-expression-on-clinical-outcome-in-paediatric-patients-with-b-cell-acute-lymphoblastic-leukaemia-preliminary-report
#15
Edyta Ulińska, Katarzyna Mycko, Elżbieta Sałacińska-Łoś, Agata Pastorczak, Alicja Siwicka, Wojciech Młynarski, Michał Matysiak
AIM OF THE STUDY: To characterise expression of mTOR (mammalian target of rapamycin) in childhood B-cell acute lymphoblastic leukaemia (ALL), and to evaluate a possible link between mTOR and clinical characteristics. MATERIAL AND METHODS: The examined group consisted of 21 consecutive patients, aged 1-18 years, diagnosed with B-cell ALL in 2010, and 10 relapsed B-cell ALL patients diagnosed for the first time between 2009 and 2011, who developed relapse before 2014...
2016: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/27599459/proteasome-subunit-expression-analysis-and-chemosensitivity-in-relapsed-paediatric-acute-leukaemia-patients-receiving-bortezomib-containing-chemotherapy
#16
Denise Niewerth, Gertjan J L Kaspers, Gerrit Jansen, Johan van Meerloo, Sonja Zweegman, Gaye Jenkins, James A Whitlock, Stephen P Hunger, Xiaomin Lu, Todd A Alonzo, Peter M van de Ven, Terzah M Horton, Jacqueline Cloos
BACKGROUND: Drug combinations of the proteasome inhibitor bortezomib with cytotoxic chemotherapy are currently evaluated in phase 2 and 3 trials for the treatment of paediatric acute myeloid leukaemia (AML) and acute lymphocytic leukaemia (ALL). METHODS: We investigated whether expression ratios of immunoproteasome to constitutive proteasome in leukaemic cells correlated with response to bortezomib-containing re-induction chemotherapy in patients with relapsed and refractory acute leukaemia, enrolled in two Children's Oncology Group phase 2 trials of bortezomib for ALL (COG-AALL07P1) and AML (COG-AAML07P1)...
September 6, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27545902/nutritional-interventions-for-survivors-of-childhood-cancer
#17
REVIEW
Jennifer E Cohen, Claire E Wakefield, Richard J Cohn
BACKGROUND: Childhood cancer survivors are at a higher risk of developing health conditions such as osteoporosis, and cardiovascular disease than their peers. Health-promoting behaviour, such as consuming a healthy diet, could lessen the impact of these chronic issues, yet the prevalence rate of health-protecting behaviour amongst survivors of childhood cancer is similar to that of the general population. Targeted nutritional interventions may prevent or reduce the incidence of these chronic diseases...
August 22, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27524528/pattern-of-relapse-in-paediatric-acute-lymphoblastic-leukaemia-in-a-tertiary-care-unit
#18
Emad Uddin Siddiqui, Sayyeda Ghazala Kazi, Muhammad Irfan Habib, Khalid Mehmood Ahmed Khan, Nukhba Zia
OBJECTIVE: To determine the frequency, site and time to relapse from diagnosis, and to see the relationship of relapse with important prognostic factors. METHODS: The prospective descriptive observational study was conducted at the National Institute of Child Health, Karachi, June 2005 to May 2007, and comprised newly-diagnosed cases of acute lymphoblastic leukaemia. Bone marrow aspiration was done on reappearance of blast cells in peripheral smear and cerebrospinal fluid...
August 2016: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/27506447/transcriptional-regulation-of-the-proto-oncogene-zfp521-by-spi1-pu-1-and-hoxc13
#19
Ming Yu, Salma Al-Dallal, Latifa Al-Haj, Shiraj Panjwani, Akina S McCartney, Sarah M Edwards, Pooja Manjunath, Catherine Walker, Alexander Awgulewitsch, Kathryn E Hentges
The mouse zinc-finger gene Zfp521 (also known as ecotropic viral insertion site 3; Evi3; and ZNF521 in humans) has been identified as a B-cell proto-oncogene, causing leukemia in mice following retroviral insertions in its promoter region that drive Zfp521 over-expression. Furthermore, ZNF521 is expressed in human hematopoietic cells, and translocations between ZNF521 and PAX5 are associated with pediatric acute lymphoblastic leukemia. However, the regulatory factors that control Zfp521 expression directly have not been characterized...
October 2016: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/27470916/whole-exome-sequencing-reveals-the-spectrum-of-gene-mutations-and-the-clonal-evolution-patterns-in-paediatric-acute-myeloid-leukaemia
#20
Norio Shiba, Kenichi Yoshida, Yuichi Shiraishi, Yusuke Okuno, Genki Yamato, Yusuke Hara, Yasunobu Nagata, Kenichi Chiba, Hiroko Tanaka, Kiminori Terui, Motohiro Kato, Myoung-Ja Park, Kentaro Ohki, Akira Shimada, Junko Takita, Daisuke Tomizawa, Kazuko Kudo, Hirokazu Arakawa, Souichi Adachi, Takashi Taga, Akio Tawa, Etsuro Ito, Keizo Horibe, Masashi Sanada, Satoru Miyano, Seishi Ogawa, Yasuhide Hayashi
Acute myeloid leukaemia (AML) is a molecularly and clinically heterogeneous disease. Targeted sequencing efforts have identified several mutations with diagnostic and prognostic values in KIT, NPM1, CEBPA and FLT3 in both adult and paediatric AML. In addition, massively parallel sequencing enabled the discovery of recurrent mutations (i.e. IDH1/2 and DNMT3A) in adult AML. In this study, whole-exome sequencing (WES) of 22 paediatric AML patients revealed mutations in components of the cohesin complex (RAD21 and SMC3), BCORL1 and ASXL2 in addition to previously known gene mutations...
July 29, 2016: British Journal of Haematology
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