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Pediatric leukemias

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https://www.readbyqxmd.com/read/28427923/-acute-leukemia-revealed-by-bone-magnetic-resonance-imaging-two-pediatric-case-reports
#1
C Flatrès, A Pennanéach, G Blondin, E Rivoal, S Haro, P Vic
Bone and joint pain are common causes of pediatric consultation for a variety of etiologies. The causes are mostly traumatic or infectious or have an inflammatory origin. Acute leukemia (AL) can sometimes begin with osteoarticular signs and radiological investigations such as magnetic resonance imaging (MRI) can help guide the diagnosis. We report on two cases of pediatric AL revealed by osteoarticular signs, with MRI helpful in the diagnostic procedure. In these children, the first signs were recurrent joint pain, with no blood count anomalies...
April 17, 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28426850/second-primary-malignant-neoplasms-and-survival-in-adolescent-and-young-adult-cancer-survivors
#2
Theresa H M Keegan, Archie Bleyer, Aaron S Rosenberg, Qian Li, Melanie Goldfarb
Importance: Although the increased incidence of second primary malignant neoplasms (SPMs) is a well-known late effect after cancer, few studies have compared survival after an SPM to survival of the same cancer occurring as first primary malignant neoplasm (PM) by age. Objective: To assess the survival impact of SPMs in adolescents and young adults (AYAs) (15-39 years) compared with that of pediatric (<15 years) and older adult (≥40 years) patients with the same SPMs...
April 20, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28423696/improvement-of-dexamethasone-sensitivity-by-chelation-of-intracellular-ca2-in-pediatric-acute-lymphoblastic-leukemia-cells-through-the-prosurvival-kinase-erk1-2-deactivation
#3
Souleymane Abdoul-Azize, Isabelle Dubus, Jean-Pierre Vannier
Previous studies have demonstrated that glucocorticoid hormones, including dexamethasone, induced alterations in intracellular calcium homeostasis in acute lymphoblastic leukemia (ALL) cells. However, the mechanism by which intracellular calcium homeostasis participates in dexamethasone sensitivity and resistance on ALL cells remains elusive. Here, we found that treatment of cells with dexamethasone resulted in increased intracellular calcium concentrations through store-operated calcium entry stimulation, which was curtailed by store-operated calcium channel blockers...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423502/acute-lymphoblastic-leukemia-cells-are-sensitive-to-disturbances-in-protein-homeostasis-induced-by-proteasome-deubiquitinase-inhibition
#4
Magdalena Mazurkiewicz, Ellin-Kristina Hillert, Xin Wang, Paola Pellegrini, Maria Hägg Olofsson, Karthik Selvaraju, Padraig D'Arcy, Stig Linder
The non-genotoxic nature of proteasome inhibition makes it an attractive therapeutic option for the treatment of pediatric malignancies. We recently described the small molecule VLX1570 as an inhibitor of proteasome deubiquitinase (DUB) activity that induces proteotoxic stress and apoptosis in cancer cells. Here we show that acute lymphoblastic leukemia (ALL) cells are highly sensitive to treatment with VLX1570, resulting in the accumulation of polyubiquitinated proteasome substrates and loss of cell viability...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422613/the-impact-of-prospective-telemedicine-implementation-in-the-management-of-childhood-acute-lymphoblastic-leukemia-in-recife-brazil
#5
Francisco Pedrosa, Faisal Shaikh, Gaston Rivera, Raul Ribeiro, Ibrahim Qaddoumi
BACKGROUND: A gap in childhood cancer outcomes remains between developed and developing countries. Persistence of this gap may be caused by financial, social, or educational disparities. Twinning and distance learning initiatives may improve such disparities. Integrating telemedicine into pediatric oncology twinning programs enhances education and facilitates patient-centered capacity building. MATERIALS AND METHODS: We performed an analysis of Web-based meetings held from August 2005 through July 2009 between the International Outreach Program at St...
April 19, 2017: Telemedicine Journal and E-health: the Official Journal of the American Telemedicine Association
https://www.readbyqxmd.com/read/28419486/population-pharmacokinetic-analysis-of-bortezomib-in-pediatric-leukemia-patients-model-based-support-for-body-surface-area-based-dosing-over-the-2-to-16-year-age-range
#6
Michael J Hanley, Diane R Mould, Timothy J Taylor, Neeraj Gupta, Kaveri Suryanarayan, Rachel Neuwirth, Dixie-Lee Esseltine, Terzah M Horton, Richard Aplenc, Todd A Alonzo, Xiaomin Lu, Ashley Milton, Karthik Venkatakrishnan
This population analysis described the pharmacokinetics of bortezomib after twice-weekly, repeat-dose, intravenous administration in pediatric patients participating in 2 clinical trials: the phase 2 AALL07P1 (NCT00873093) trial in relapsed acute lymphoblastic leukemia and the phase 3 AAML1031 (NCT01371981) trial in de novo acute myelogenous leukemia. The sources of variability in the pharmacokinetic parameters were characterized and quantified to support dosing recommendations. Patients received intravenous bortezomib 1...
April 18, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28416749/acute-lymphoblastic-leukemia-cells-are-sensitive-to-disturbances-in-protein-homeostasis-induced-by-proteasome-deubiquitinase-inhibition
#7
Magdalena Mazurkiewicz, Ellin-Kristina Hillert, Xin Wang, Paola Pellegrini, Maria Hägg Olofsson, Karthik Selvaraju, Padraig D'Arcy, Stig Linder
The non-genotoxic nature of proteasome inhibition makes it an attractive therapeutic option for the treatment of pediatric malignancies. We recently described the small molecule VLX1570 as an inhibitor of proteasome deubiquitinase (DUB) activity that induces proteotoxic stress and apoptosis in cancer cells. Here we show that acute lymphoblastic leukemia (ALL) cells are highly sensitive to treatment with VLX1570, resulting in the accumulation of polyubiquitinated proteasome substrates and loss of cell viability...
February 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415763/low-numbers-of-pre-leukemic-fusion-genes-are-frequently-present-in-umbilical-cord-blood-without-affecting-dna-damage-response
#8
Pavol Kosik, Milan Skorvaga, Matus Durdik, Lukas Jakl, Ekaterina Nikitina, Eva Markova, Katarina Kozics, Eva Horvathova, Igor Belyaev
Despite widely accepted notion that many childhood leukemias are likely developed from hematopoietic stem/progenitor cells (HSPC) with pre-leukemic fusion genes (PFG) formed in embryonic/fetal development, the data on PFG incidence in newborns are contradictive. To provide a better understanding of a prenatal origin of leukemia, umbilical cord blood from 500 newborns was screened for the presence of the most frequent PFG associated with pediatric B-cell acute lymphoblastic leukemia. This screening revealed relatively high incidence of ETV6-RUNX1, BCR-ABL1 (p190) and MLL-AF4 at very low frequencies, averaging ~14 copies per 100,000 cells...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415601/regulatory-network-of-gata3-in-pediatric-acute-lymphoblastic-leukemia
#9
Qianqian Hou, Fei Liao, Shouyue Zhang, Duyu Zhang, Yan Zhang, Xueyan Zhou, Xuyang Xia, Yuanxin Ye, Hanshuo Yang, Zhaozhi Li, Leiming Wang, Xi Wang, Zhigui Ma, Yiping Zhu, Liang Ouyang, Yuelan Wang, Hui Zhang, Li Yang, Heng Xu, Yang Shu
GATA3 polymorphisms were reported to be significantly associated with susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism located around in the tissue-specific enhancer, and significantly associated with GATA3 expression. Although the regulatory network of GATA3 has been well reported in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus conducted genome-wide gene expression association analyses to reveal expression associated genes and pathways in nine independent B-ALL patient cohorts...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415578/high-expression-of-mir-125b-2-and-snord116-noncoding-rna-clusters-characterize-erg-related-b-cell-precursor-acute-lymphoblastic-leukemia
#10
Elena Vendramini, Marco Giordan, Emanuela Giarin, Barbara Michielotto, Grazia Fazio, Gianni Cazzaniga, Andrea Biondi, Daniela Silvestri, Maria Grazia Valsecchi, Martina U Muckenthaler, Andreas E Kulozik, Valter Gattei, Shai Izraeli, Giuseppe Basso, Geertruy Te Kronnie
ERG-related leukemia is a B cell precursor acute lymphoblastic leukemia (BCP ALL) subtype characterized by aberrant expression of DUX4 and ERG transcription factors, and highly recurrent ERG intragenic deletions. ERG-related patients have remarkably favorable outcome despite a high incidence of inauspicious IKZF1 aberrations.We describe clinical and genomic features of the ERG-related cases in an unselected cohort of B-other BCP ALL pediatric patients enrolled in the AIEOP ALL 2000 therapeutic protocol. We report a small noncoding RNA signature specific of ERG-related group, with up-regulation of miR-125b-2 cluster on chromosome 21 and several snoRNAs in the Prader-Willi locus at 15q11...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414188/a-case-of-splenomegaly-in-cbl-syndrome
#11
Rachel R Coe, Margaret L McKinnon, Maja Tarailo-Graovac, Colin J Ross, Wyeth W Wasserman, Jan M Friedman, Paul C Rogers, Clara D M van Karnebeek
INTRODUCTION: We present a child with unexplained splenomegaly to highlight this feature as a presenting sign of the RASopathy CBL syndrome and to draw attention to the power and utility of next generation genomic sequencing for providing rapid diagnosis and critical information to guide care in the pediatric clinical setting. CLINICAL REPORT: A 7-year-old boy presented with unexplained splenomegaly, attention deficit hyperactivity disorder, mild learning difficulties, easy bruising, mild thrombocytopenia, and subtle dysmorphic features...
April 13, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28412998/new-hpsc-based-human-models-to-study-pediatric-acute-megakaryoblastic-leukemia-harboring-the-fusion-oncogene-rbm15-mkl1
#12
Verónica Ayllón, Marina Vogel-González, Federico González-Pozas, Joan Domingo-Reinés, Rosa Montes, Lucía Morales-Cacho, Verónica Ramos-Mejía
Pediatric Acute Megakaryoblastic Leukemia not associated to Down Syndrome (non-DS AMKL) is a rare disease with a dismal prognosis. Around 15% of patients carry the chromosomal translocation t(1;22) that originates the fusion oncogene RBM15-MKL1, which is linked to an earlier disease onset (median of 6months of age) and arises in utero. Here we report the generation of two hPSC cell lines constitutively expressing the oncogene RBM15-MKL1, resulting in an increased expression of known RBM15-MKL1 gene targets...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28412288/adult-t-type-lymphoblastic-lymphoma-treatment-advances-and-prognostic-indicators
#13
REVIEW
Stéphane Lepretre, Carlos Graux, Aurore Touzart, Elizabeth Macintyre, Nicolas Boissel
T-cell lymphoblastic lymphoma (T-LBL) is a rare, aggressive neoplasm of precursor T cells that occurs mostly in adolescents and young adults. In this review, we describe the treatment of adult T-LBL with a focus on recent advances using pediatric-inspired acute lymphoblastic leukemia regimens, which have greatly improved outcome. We also discuss the development of prognostic indicators for T-LBL, especially oncogenetic factors, that can identify patients at higher risk of relapse and should help further extend T-LBL patient survival...
April 12, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28411282/genomic-architecture-and-treatment-outcome-in-pediatric-acute-myeloid-leukemia-a-children-s-oncology-group-report
#14
Marijana Vujkovic, Edward F Attiyeh, Rhonda E Ries, Elizabeth K Goodman, Yang Ding, Marko Kavcic, Todd A Alonzo, Yi-Cheng Wang, Robert B Gerbing, Lillian Sung, Betsy Hirsch, Susana Raimondi, Alan S Gamis, Soheil Meshinchi, Richard Aplenc
Childhood acute myeloid leukemia (AML) is frequently characterized by chromosomal instability. Approximately 50% of patients have disease relapse, and novel prognostic markers are needed to improve risk stratification. We performed genome-wide genotyping in 446 pediatric patients with de novo AML enrolled on Children's Oncology Group (COG) studies, AAML0531 (NCT01407757), AAML03P1 (NCT00070174), and CCG2961 (NCT00003790). Affymetrix and Illumina Omni 2.5 platforms were used to evaluate copy number alterations (CNAs) and determine their associations with treatment outcome...
April 14, 2017: Blood
https://www.readbyqxmd.com/read/28411197/correction-mutational-landscape-of-pediatric-acute-lymphoblastic-leukemia
#15
(no author information available yet)
No abstract text is available yet for this article.
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28410182/parent-and-health-care-provider-perceptions-for-development-of-a-web-based-weight-management-program-for-survivors-of-pediatric-acute-lymphoblastic-leukemia-a-mixed-methods-study
#16
Sara Folta, Winnie Chang, Rachel Hill, Michael Kelly, Susan Meagher, W Paul Bowman, Fang Fang Zhang
BACKGROUND: Survivors of pediatric acute lymphoblastic leukemia (ALL) may experience unhealthy weight gain during treatment, which has been associated with higher risk for chronic health issues. OBJECTIVE: The purpose of this study was to obtain feedback on weight management in pediatric ALL survivors and on the content and implementation of a Web-based weight management program. METHODS: Study participants included 54 parent survey respondents and 19 pediatric oncology professionals in 4 focus groups...
February 9, 2017: JMIR Cancer
https://www.readbyqxmd.com/read/28409853/a-phase-1-study-of-the-cxcr4-antagonist-plerixafor-in-combination-with-high-dose-cytarabine-and-etoposide-in-children-with-relapsed-or-refractory-acute-leukemias-or-myelodysplastic-syndrome-a-pediatric-oncology-experimental-therapeutics-investigators-consortium
#17
Todd M Cooper, Edward Allan Racela Sison, Sharyn D Baker, Lie Li, Amina Ahmed, Tanya Trippett, Lia Gore, Margaret E Macy, Aru Narendran, Keith August, Michael J Absalon, Jessica Boklan, Jessica Pollard, Daniel Magoon, Patrick A Brown
BACKGROUND: Plerixafor, a reversible CXCR4 antagonist, inhibits interactions between leukemic blasts and the bone marrow stromal microenvironment and may enhance chemosensitivity. A phase 1 trial of plerixafor in combination with intensive chemotherapy in children and young adults with relapsed or refractory acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) was performed to determine a tolerable and biologically active dose. PROCEDURE: Plerixafor was administered daily for 5 days at four dose levels (6, 9, 12, and 15 mg/m(2) /dose) followed 4 hr later by high-dose cytarabine (every 12 hr) and etoposide (daily)...
April 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28405496/il-12-il-15-and-il-18-pre-activated-nk-cells-target-resistant-t-cell-acute-lymphoblastic-leukemia-and-delay-leukemia-development-in-vivo
#18
Margherita Boieri, Aina Ulvmoen, Amanda Sudworth, Clare Lendrem, Matthew Collin, Anne M Dickinson, Lise Kveberg, Marit Inngjerdingen
NK cells have shown promise in therapy of hematological cancers, in particular against acute myeloid leukemia. In contrast, the more NK cell-resistant acute lymphoblastic leukemia (ALL) is difficult to treat with NK-cell-based therapies, and we hypothesized that pre-activation of NK cells could overcome this resistance. We show in pediatric and adult patients with T-cell ALL (T-ALL) perturbed NK cell effector functions at diagnosis. Using an in vivo rat model for T-ALL, Roser leukemia (RL), suppressed NK cell effector functions were observed...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28401497/bortezomib-combined-with-standard-induction-chemotherapy-in-japanese-children-with-refractory-acute-lymphoblastic-leukemia
#19
Akihiro Iguchi, Yuko Cho, Minako Sugiyama, Yukayo Terashita, Tadashi Ariga, Yosuke Hosoya, Shinsuke Hirabayashi, Atsushi Manabe, Keisuke Hara, Tetsuya Aiba, Tsugumi Shiokawa, Hiroko Tada, Norihiro Sato
Bortezomib has been shown to be effective and well-tolerated in patients with refractory acute lymphoblastic leukemia (ALL) in the Therapeutic Advances in Childhood Leukemia trial. However, the safety and efficacy of bortezomib have not been evaluated in Japanese pediatric patients. Here, we report the results of a clinical trial designed to evaluate the safety of bortezomib combined with induction chemotherapy in Japanese children with refractory ALL. A total of six patients with B-precursor ALL were enrolled in this study...
April 11, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28401483/molecular-profiling-of-gene-copy-number-abnormalities-in-key-regulatory-genes-in-high-risk-b-lineage-acute-lymphoblastic-leukemia-frequency-and-their-association-with-clinicopathological-findings-in-indian-patients
#20
Prerana Bhandari, Firoz Ahmad, Bibhu Ranjan Das
Genes related to key cellular pathways are frequently altered in B cell ALL and are associated with poor survival especially in high-risk (HR) subgroups. We examined gene copy number abnormalities (CNA) in 101 Indian HR B cell ALL patients and their correlation with clinicopathological features by multiplex ligation-dependent probe amplification. Overall, CNA were detected in 59 (59%) cases, with 26, 10 and 23% of cases harboring 1, 2 or +3 CNA. CNA were more prevalent in BCR-ABL1 (60%), pediatric (64%) and high WCC (WBC count) (63%) patients...
May 2017: Medical Oncology
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