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childhood acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/29348612/gwas-in-childhood-acute-lymphoblastic-leukemia-reveals-novel-genetic-associations-at-chromosomes-17q12-and-8q24-21
#1
Joseph L Wiemels, Kyle M Walsh, Adam J de Smith, Catherine Metayer, Semira Gonseth, Helen M Hansen, Stephen S Francis, Juhi Ojha, Ivan Smirnov, Lisa Barcellos, Xiaorong Xiao, Libby Morimoto, Roberta McKean-Cowdin, Rong Wang, Herbert Yu, Josephine Hoh, Andrew T DeWan, Xiaomei Ma
Childhood acute lymphoblastic leukemia (ALL) (age 0-14 years) is 20% more common in Latino Americans than non-Latino whites. We conduct a genome-wide association study in a large sample of 3263 Californian children with ALL (including 1949 of Latino heritage) and 3506 controls matched on month and year of birth, sex, and ethnicity, and an additional 12,471 controls from the Kaiser Resource for Genetic Epidemiology Research on Aging Cohort. Replication of the strongest genetic associations is performed in two independent datasets from the Children's Oncology Group and the California Childhood Leukemia Study...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339403/a-phase-1-study-of-azacitidine-combined-with-chemotherapy-in-childhood-leukemia-a-report-from-tacl-consortium
#2
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/29335448/regional-evaluation-of-childhood-acute-lymphoblastic-leukemia-genetic-susceptibility-loci-among-japanese
#3
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/29333004/drosha-rs642321-polymorphism-influence-susceptibility-to-childhood-acute-lymphoblastic-leukemia-a-preliminary-report
#4
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/29304394/perforin-gene-variation-influences-survival-in-childhood-acute-lymphoblastic-leukemia
#5
Aleksandra Jaworowska, Agata Pastorczak, Joanna Trelinska, Kamila Wypyszczak, Maciej Borowiec, Wojciech Fendler, Lukasz Sedek, Tomasz Szczepanski, Rafal Ploski, Wojciech Młynarski
Although a growing body of data links mutations in the perforin gene with increased susceptibility to hematologic malignancies, no studies discuss their influence on the clinical course of such diseases. The present study examines the impact of perforin gene variation on the clinical outcome in acute lymphoblastic leukemia (ALL) patients. The study enrolled 312 children aged 1-18 years, treated for ALL. PRF1 gene variants were analyzed through direct DNA sequencing. Variation in rs885822 was found to be associated with overall survival: patients carrying the GG genotype demonstrated a significantly increased risk of death compared to those carrying the A allele, independently of ALL risk groups (HR 3...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29303026/risk-factors-for-impaired-pulmonary-function-and-cardiorespiratory-fitness-in-very-long-term-adult-survivors-of-childhood-acute-lymphoblastic-leukemia-after-treatment-with-chemotherapy-only
#6
Ole Henrik Myrdal, Adriani Kanellopoulos, Jon R Christensen, Ellen Ruud, Elisabeth Edvardsen, Johny Kongerud, Liv Ingunn Sikkeland, May B Lund
BACKGROUND: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk of late treatment-related side-effects. Data regarding prevalence and risk factors for impairments in pulmonary function and cardiorespiratory fitness are limited, and reported findings are inconsistent and inconclusive. MATERIAL AND METHODS: In a cross-sectional study, 116 ALL survivors (median 5 years at diagnosis, 29 years at follow-up, 53% females) were examined, median 23 years after treatment with chemotherapy only...
January 5, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29300620/tp53-germline-variations-influence-the-predisposition-and-prognosis-of-b-cell-acute-lymphoblastic-leukemia-in-children
#7
Maoxiang Qian, Xueyuan Cao, Meenakshi Devidas, Wenjian Yang, Cheng Cheng, Yunfeng Dai, Andrew Carroll, Nyla A Heerema, Hui Zhang, Takaya Moriyama, Julie M Gastier-Foster, Heng Xu, Elizabeth Raetz, Eric Larsen, Naomi Winick, W Paul Bowman, Paul L Martin, Elaine R Mardis, Robert Fulton, Gerard Zambetti, Michael Borowitz, Brent Wood, Kim E Nichols, William L Carroll, Ching-Hon Pui, Charles G Mullighan, William E Evans, Stephen P Hunger, Mary V Relling, Mignon L Loh, Jun J Yang
Purpose Germline TP53 variation is the genetic basis of Li-Fraumeni syndrome, a highly penetrant cancer predisposition condition. Recent reports of germline TP53 variants in childhood hypodiploid acute lymphoblastic leukemia (ALL) suggest that this type of leukemia is another manifestation of Li-Fraumeni syndrome; however, the pattern, prevalence, and clinical relevance of TP53 variants in childhood ALL remain unknown. Patients and Methods Targeted sequencing of TP53 coding regions was performed in 3,801 children from the Children's Oncology Group frontline ALL clinical trials, AALL0232 and P9900...
January 4, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29290585/a-human-ips-model-implicates-embryonic-b-myeloid-fate-restriction-as-developmental-susceptibility-to-b%C3%A2-acute-lymphoblastic-leukemia-associated-etv6-runx1
#8
Charlotta Böiers, Simon E Richardson, Emma Laycock, Alya Zriwil, Virginia A Turati, John Brown, Jason P Wray, Dapeng Wang, Chela James, Javier Herrero, Ewa Sitnicka, Stefan Karlsson, Andrew J H Smith, Sten Erik W Jacobsen, Tariq Enver
ETV6-RUNX1 is associated with childhood acute B-lymphoblastic leukemia (cALL) functioning as a first-hit mutation that initiates a clinically silent pre-leukemia in utero. Because lineage commitment hierarchies differ between embryo and adult, and the impact of oncogenes is cell-context dependent, we hypothesized that the childhood affiliation of ETV6-RUNX1 cALL reflects its origins in a progenitor unique to embryonic life. We characterize the first emerging B cells in first-trimester human embryos, identifying a developmentally restricted CD19-IL-7R+ progenitor compartment, which transitions from a myeloid to lymphoid program during ontogeny...
December 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29286560/modifying-bone-mineral-density-physical-function-and-quality-of-life-in-children-with-acute-lymphoblastic-leukemia
#9
Cheryl L Cox, Liang Zhu, Sue C Kaste, Kumar Srivastava, Linda Barnes, Paul C Nathan, Robert J Wells, Kirsten K Ness
BACKGROUND: The early effects of childhood acute lymphoblastic leukemia (ALL) include decreased physical function, bone mineral density (BMD/g/cm2 ), and health-related quality of life (HRQL). We assessed the capacity of a physical therapy and motivation-based intervention, beginning after diagnosis and continuing through the end of treatment, to positively modify these factors. PROCEDURE: A 2.5-year randomized controlled trial of 73 patients aged 4-18.99 years within 10 days of ALL diagnosis assessed BMD at baseline (T0 ) and end of therapy (T3 ), strength, range of motion, endurance, motor skills, and HRQL at baseline (T0 ), 8 (T1 ), 15 (T2 ), and 135 (T3 ) weeks...
December 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29282364/mir-pharmacogenetics-of-vincristine-and-peripheral-neurotoxicity-in-childhood-b-cell-acute-lymphoblastic-leukemia
#10
Ángela Gutierrez-Camino, Maitane Umerez, Idoia Martin-Guerrero, Nagore García de Andoin, Borja Santos, Ana Sastre, Aizpea Echebarria-Barona, Itziar Astigarraga, Aurora Navajas, Africa Garcia-Orad
Vincristine (VCR), an important component of childhood acute lymphoblastic leukemia (ALL) therapy, can cause sensory and motor neurotoxicity. This neurotoxicity could lead to dose reduction or treatment discontinuation, which could in turn reduce survival. In this line, several studies associated peripheral neurotoxicity and polymorphisms in genes involved in pharmacokinetics (PK) and pharmacodynamics (PD) of VCR. Nowadays, it is well known that these genes are regulated by microRNAs (miRNAs) and SNPs in miRNAs could modify their levels or function...
December 27, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29282361/influence-of-bcl2l11-polymorphism-on-osteonecrosis-during-treatment-of-childhood-acute-lymphoblastic-leukemia
#11
Maria Plesa, Vincent Gagné, Sanja Glisovic, Melissa Younan, Bahram Sharif-Askari, Caroline Laverdière, Nathalie Alos, Jean-Marie Leclerc, Stephen E Sallan, Donna Neuberg, Jeffery L Kutok, Lewis B Silverman, Daniel Sinnett, Maja Krajinovic
Osteonecrosis (ON) is corticosteroid-related complication, reported in children with acute lymphoblastic leukemia (ALL). We have previously found that polymorphisms in BCL2L11 gene coding for pro-apoptotic Bim protein influence reduction of overall survival (OS) in a corticosteroid (CS) dose-dependent manner in childhood ALL patients. The same set of SNPs was here investigated for an association with CS-related ON assessed retrospectively in 304 children with ALL from Quebec (QcALL cohort) who received Dana-Farber Cancer Institute (DFCI) ALL treatment protocols...
December 27, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29260390/parent-perspectives-and-preferences-for-strategies-regarding-nonsedated-mri-scans-in-a-pediatric-oncology-population
#12
Breya Walker, Heather M Conklin, Doralina L Anghelescu, Lacey P Hall, Wilburn E Reddick, Robert Ogg, Lisa M Jacola
PURPOSE: Children with cancer frequently require MRI scans for clinical purposes. Sedation with general anesthesia (GA) is often used to promote compliance, reduce motion, and alleviate anxiety. The use of GA for MRI scans is costly in terms of time, personnel, and medications. In addition, prominent risks are associated with anesthesia exposure in patients with complex medical conditions. Successful behavioral interventions have been implemented in clinical research settings to promote scan success and compliance...
December 19, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29249823/flow-cytometric-vs-morphologic-assessment-of-remission-in-childhood-acute-lymphoblastic-leukemia-a-report-from-the-children-s-oncology-group-cog
#13
S Gupta, M Devidas, M L Loh, E A Raetz, S Chen, C Wang, P Brown, A J Carroll, N A Heerema, J M Gastier-Foster, K P Dunsmore, E C Larsen, K W Maloney, L A Mattano, S S Winter, N J Winick, W L Carroll, S P Hunger, M Borowitz, B L Wood
Minimal residual disease (MRD) after initial therapy is integral to risk stratification in B- and T-precursor acute lymphoblastic leukemia (B-ALL, T-ALL). Although MRD determines depth of remission, remission remains defined by morphology. We determined the outcomes of children with discordant assessments of remission by morphology vs flow cytometry using patients aged 1-30.99 years enrolled on Children's Oncology Group ALL trials who underwent bone marrow assessment at the end of induction (N=9350). Morphologic response was assessed locally as M1 (<5% lymphoblasts; remission), M2 (5-25%) or M3 (>25%)...
December 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29247169/cardiometabolic-risk-factors-in-childhood-adolescent-and-young-adult-survivors-of-acute-lymphoblastic-leukemia-a-petale-cohort
#14
Emile Levy, Mariia Samoilenko, Sophia Morel, Jade England, Devendra Amre, Laurence Bertout, Simon Drouin, Caroline Laverdière, Maja Krajinovic, Daniel Sinnett, Geneviève Lefebvre, Valérie Marcil
Our objectives were to assess the prevalence of cardiometabolic complications in children, adolescents, and young adult survivors of childhood acute lymphoblastic leukemia (cALL), to identify their predictors and the risk compared to the Canadian population. We performed a cardiometabolic assessment of cALL survivors from the PETALE cohort (n = 247, median age at visit of 21.7 years). In our group, overweight and obesity affected over 70% of women. Pre-hypertension and hypertension were mostly common in men, both adults (20%) and children (19%)...
December 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29244249/flow-cytometric-false-myeloperoxidase-positive-childhood-b-lineage-acute-lymphoblastic-leukemia
#15
Süreyya Savaşan, Steven Buck, Manisha Gadgeel, Ali Gabali
BACKGROUND: Flow cytometric intracellular myeloperoxidase (MPO) staining of leukemic blasts is a useful tool in diagnosis of leukemia subtype. Interpretation of high MPO-positivity can be a diagnostic challenge in B-lineage acute lymphoblastic leukemia (B-ALL). While very few such cases have been reported, high MPO positive B-ALL cases without additional myeloid antigen positivity are suspect and require further investigation. METHODS: Three pediatric cases of B-ALL with strong MPO staining (clone 8E6; Invitrogen) at diagnosis and three others with negative MPO staining were studied by flow cytometry and immunohistochemistry...
December 15, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/29238226/maternal-diabetes-and-incidence-of-childhood-cancer-a-nationwide-cohort-study-and-exploratory-genetic-analysis
#16
Anna Deleskog, Marcel den Hoed, Giorgio Tettamanti, Sofia Carlsson, Rickard Ljung, Maria Feychting, Hannah L Brooke
Background: The etiology of childhood cancer is not well understood, but may be linked to prenatal and perinatal factors, such as maternal diabetes. However, this association has not been examined in depth. We aimed to determine if maternal diabetes is associated with risk of childhood brain tumor (CBT), leukemia (all types combined and acute lymphoblastic leukemia [ALL] separately), and lymphoma. Methods: All children born in Sweden between 1973 and 2014 (n=4,239,965) were followed from birth until first cancer diagnosis, age 15 years, or December 31, 2015...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/29236701/anti-leukemic-activity-of-bortezomib-and-carfilzomib-on-b-cell-precursor-all-cell-lines
#17
Kazuya Takahashi, Takeshi Inukai, Toshihiko Imamura, Mio Yano, Chihiro Tomoyasu, David M Lucas, Atsushi Nemoto, Hiroki Sato, Meixian Huang, Masako Abe, Keiko Kagami, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Koshi Akahane, Kumiko Goi, Jiro Kikuchi, Yusuke Furukawa, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Kanji Sugita
Prognosis of childhood acute lymphoblastic leukemia (ALL) has been dramatically improved. However, prognosis of the cases refractory to primary therapy is still poor. Recent phase 2 study on the efficacy of combination chemotherapy with bortezomib (BTZ), a proteasome inhibitor, for refractory childhood ALL demonstrated favorable clinical outcomes. However, septic death was observed in over 10% of patients, indicating the necessity of biomarkers that could predict BTZ sensitivity. We investigated in vitro BTZ sensitivity in a large panel of ALL cell lines that acted as a model system for refractory ALL, and found that Philadelphia chromosome-positive (Ph+) ALL, IKZF1 deletion, and biallelic loss of CDKN2A were associated with favorable response...
2017: PloS One
https://www.readbyqxmd.com/read/29234981/sarcopenia-after-induction-therapy-in-childhood-acute-lymphoblastic-leukemia-its-clinical-significance
#18
Daisuke Suzuki, Ryoji Kobayashi, Hirozumi Sano, Daiki Hori, Kunihiko Kobayashi
Muscle weakness is one of the most serious problems during chemotherapy for childhood hematological malignancies. It may be caused by long-term hospitalization, unfavorable physical conditions, and restricted activities. Although the concept of sarcopenia is becoming widely recognized, especially in geriatric medicine, there have been few reports about sarcopenia in pediatric patients with hematological malignancies. A total of 47 consecutive first-onset acute lymphoblastic leukemia (ALL) patients who underwent induction therapy between January 2011 and September 2016 were investigated...
December 12, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29231963/body-composition-in-long-term-survivors-of-acute-lymphoblastic-leukemia-diagnosed-in-childhood-and-adolescence-a-focus-on-sarcopenic-obesity
#19
Christopher J C Marriott, Lesley F Beaumont, Troy H Farncombe, Amy N Cranston, Uma H Athale, Valerie N Yakemchuk, Colin E Webber, Ronald D Barr
BACKGROUND: The late effects of treatment for acute lymphoblastic leukemia (ALL) include disordered body composition, especially obesity. Less attention has been focused on the loss of skeletal muscle mass (SMM) and the combined morbidity of sarcopenic obesity. METHODS: A cross-sectional study of body composition was undertaken via dual-energy x-ray absorptiometry in 75 long-term survivors of ALL (more than 10 years after the diagnosis). Measures were obtained of the fat mass (FM), fat-free mass (equivalent to the lean body mass [LBM]), and whole-body bone mineral content...
December 12, 2017: Cancer
https://www.readbyqxmd.com/read/29230958/treatment-related-mortality-in-relapsed-childhood-acute-lymphoblastic-leukemia
#20
Trausti Oskarsson, Stefan Söderhäll, Johan Arvidson, Erik Forestier, Thomas Leth Frandsen, Marit Hellebostad, Päivi Lähteenmäki, Ólafur G Jónsson, Ida Hed Myrberg, Mats Heyman
BACKGROUND: Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment-related toxicity impacts survival. PROCEDURE: In this retrospective population-based study, we described the causes of death and estimated the risk for treatment-related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL-92 and ALL-2000 trials...
December 12, 2017: Pediatric Blood & Cancer
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