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https://www.readbyqxmd.com/read/28727288/complications-preceding-early-deaths-in-black-and-white-children-with-acute-myeloid-leukemia
#1
Lena E Winestone, Kelly D Getz, Tamara P Miller, Yimei Li, Yuan-Shung Huang, Alix E Seif, Brian T Fisher, Richard Aplenc
Black patients have a twofold increased risk of induction mortality compared to White patients with acute myeloid leukemia (AML). We reviewed diagnosis and billing data from Pediatric Health Information System for 28 AML Induction I deaths to investigate conditions preceding death in White and Black patients. Half of deaths occurred within 10 days of initial diagnostic admission. Respiratory, cardiac, renal, and infectious complications were common prior to both White and Black deaths. Deaths in White patients were more commonly preceded by intracranial hemorrhage compared to deaths in Black patients...
July 20, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28724437/the-lncrna-casc15-regulates-sox4-expression-in-runx1-rearranged-acute-leukemia
#2
Thilini R Fernando, Jorge R Contreras, Matteo Zampini, Norma I Rodriguez-Malave, Michael O Alberti, Jaime Anguiano, Tiffany M Tran, Jayanth K Palanichamy, Jasmine Gajeton, Nolan M Ung, Cody J Aros, Ella V Waters, David Casero, Giuseppe Basso, Martina Pigazzi, Dinesh S Rao
BACKGROUND: Long non-coding RNAs (lncRNAs) play a variety of cellular roles, including regulation of transcription and translation, leading to alterations in gene expression. Some lncRNAs modulate the expression of chromosomally adjacent genes. Here, we assess the roles of the lncRNA CASC15 in regulation of a chromosomally nearby gene, SOX4, and its function in RUNX1/AML translocated leukemia. RESULTS: CASC15 is a conserved lncRNA that was upregulated in pediatric B-acute lymphoblastic leukemia (B-ALL) with t (12; 21) as well as pediatric acute myeloid leukemia (AML) with t (8; 21), both of which are associated with relatively better prognosis...
July 19, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28710806/clinical-features-and-prognostic-impact-of-prdm16-expression-in-adult-acute-myeloid-leukemia
#3
Genki Yamato, Hiroki Yamaguchi, Hiroshi Handa, Norio Shiba, Machiko Kawamura, Satoshi Wakita, Koiti Inokuchi, Yusuke Hara, Kentaro Ohki, Jun Okubo, Myoung-Ja Park, Manabu Sotomatsu, Hirokazu Arakawa, Yasuhide Hayashi
High PRDM16 (also known as MEL1) expression is a representative marker of acute myeloid leukemia (AML) with NUP98-NSD1 and is a significant predictive marker for poor prognosis in pediatric AML. However, the clinical features of adult AML with PRDM16 expression remain unclear. PRDM16 is highly homologous to MDS1/EVI1, which is an alternatively spliced transcript of MECOM (also known as EVI1). We investigated PRDM16 expression in 151 AML patients, with 47 (31%) exhibiting high PRDM16 expression (PRDM16/ABL1 ratio ≥ 0...
July 14, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28701730/the-mll-recombinome-of-acute-leukemias-in-2017
#4
C Meyer, T Burmeister, D Gröger, G Tsaur, L Fechina, S Renneville, R Sutton, N C Venn, M Emerenciano, M S Pombo-de-Oliveira, C Barbieri Blunck, B Almeida Lopes, J Zuna, J Trka, P Ballerini, H Lapillonne, M De Braekeleer, G Cazzaniga, L Corral Abascal, V H J van der Velden, E Delabesse, T S Park, S H Oh, M L M Silva, T Lund-Aho, V Juvonen, A S Moore, O Heidenreich, J Vormoor, E Zerkalenkova, Y Olshanskaya, C Bueno, P Menendez, S Teigler-Schlegel, U Zur Stadt, J Lentes, G Göhring, S Kustanovich, O Aleinikova, B W Schäfer, S Kubetzko, H O Madsen, B Gruhn, X Duarte, P Gameiro, E Lippert, S Bidet, J M Cayuela, E Clappier, C N Alonso, C M Zwaan, M M van den Heuvel-Eibrink, S Izraeli, L Trakhtenbrot, P Archer, J Hancock, A Möricke, J Alten, M Schrappe, M Stanulla, S Strehl, A Attarbaschi, M Dworzak, O A Haas, R Panzer-Grümayer, L Sedék, T Szczepański, S Caye, L Suarez, H Cavé, R Marschalek
Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here, we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements habe been identified so far, of which 94 TPGs are now characterized at the molecular level. Thirty-five out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene...
July 13, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28694182/allogeneic-hematopoietic-stem-cell-transplantation-with-myeloablative-conditioning-is-associated-with-favorable-outcomes-in-mixed-phenotype-acute-leukemia
#5
Bartlomiej M Getta, Mikhail Roshal, Junting Zheng, Jae H Park, Eytan M Stein, Ross Levine, Esperanza B Papadopoulos, Ann A Jakubowski, Nancy A Kernan, Peter Steinherz, Richard J O'Reilly, Miguel-Angel Perales, Sergio A Giralt, Martin S Tallman, Brian C Shaffer
Mixed phenotype acute leukemia (MPAL) represents a poorly characterized group of acute leukemias that lack an accepted therapeutic approach and are typically associated with poor outcomes. We present our experience of genomic profiling, pre-transplant therapy and transplant outcomes for 36 well characterized pediatric and adult patients with MPAL defined according to the 2016 WHO leukemia update. A predominance of ALL-associated mutations and cytogenetic abnormalities was noted. Remission rates after induction appeared comparable among adults (20/23) and children (11/13) and among those who received ALL (10/11) or AML-type (21/25) induction...
July 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28680749/tumor-priming-converts-nk-cells-to-memory-like-nk-cells
#6
Marina Pal, Lisa Schwab, Anastasiya Yermakova, Emily M Mace, Rainer Claus, Ann-Christin Krahl, Jeanette Woiterski, Udo F Hartwig, Jordan S Orange, Rupert Handgretinger, Maya C André
Fascinating earlier evidence suggests an intrinsic capacity of human natural killer (NK) cells to acquire adaptive immune features in the context of cytomegalovirus (CMV) infection or pro-inflammatory cytokine stimulation. Since the role of memory NK cells in cancer has so far remained elusive and adoptive NK cell transfer in relapsing pediatric acute B cell precursor leukemia (BCP-ALL) patients awaits improvement, we asked the question whether tumor-priming could promote the generation of memory NK cells with enhanced graft-vs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28670435/acute-myeloid-leukemia-with-ram-immunophenotype-a-pediatric-case-with-unusual-morphologic-features
#7
Miriam Conces, Rolla Abu-Arja, Suzanne Reed, Hemalatha G Rangarajan, Terri L Guinipero, Michael R Loken, Lisa Eidenschink Brodersen, Samir B Kahwash
The RAM immunophenotype has been recently described as a subtype of acute myelogenous leukemia (AML) that is characterized clinically by extremely poor prognosis. We present a case of AML with RAM immunophenotype in a 5-year-old patient that resulted in poor outcome despite early hematopoietic cell transplant. We describe the unusual morphologic features that, along with the distinct immunophenotype, may provide initial diagnostic clues and further justify the classification of this AML variant as a rather distinct subtype...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28658145/central-hypothyroidism-in-a-pediatric-case-of-primary-acute-monoblastic-leukemia-with-central-nervous-system-infiltration-a-case-report
#8
Yuya Sato, Satomi Koyama, Shigeko Kuwashima, Masaya Kato, Mayuko Okuya, Keitaro Fukushima, Hidemitsu Kurosawa, Osamu Arisaka
RATIONALE: Central nervous system (CNS) leukemia is a frequent diagnosis in pediatric acute myeloblastic leukemia (AML) and includes neural symptoms. However, CNS leukemia is rarely associated with central hypsothyroidism. PATIENT CONCERNS AND DIAGNOSES: A 2-year-old female with AML with MLL rearrangement presented with CNS infiltration. Laboratory tests suggested the presence of central hypothyroidism (thyroid-stimulating hormone [TSH]: 0.48 mIU/ml, normal range 0...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28655787/cytosine-deaminase-apobec3a-sensitizes-leukemia-cells-to-inhibition-of-the-dna-replication-checkpoint
#9
Abby M Green, Konstantin Budagyan, Katharina E Hayer, Morgann A Reed, Milan R Savani, Gerald B Wertheim, Matthew D Weitzman
Mutational signatures in cancer genomes have implicated the APOBEC3 cytosine deaminases in oncogenesis, possibly offering a therapeutic vulnerability. Elevated APOBEC3B expression has been detected in solid tumors, but expression of APOBEC3A (A3A) in cancer has not been described to date. Here we report that A3A is highly expressed in subsets of pediatric and adult acute myeloid leukemia (AML). We modeled A3A expression in the THP1 AML cell line by introducing an inducible A3A gene. A3A expression caused ATR-dependent phosphorylation of Chk1 and cell cycle arrest, consistent with replication checkpoint activation...
June 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/28655785/a-small-molecule-inhibitor-of-wee1-azd1775-synergizes-with-olaparib-by-impairing-homologous-recombination-and-enhancing-dna-damage-and-apoptosis-in-acute-leukemia
#10
Tamara B Garcia, Jonathan C Snedeker, Dmitry Baturin, Lori Gardner, Susan P Fosmire, Chengjing Zhou, Craig T Jordan, Sujatha Venkataraman, Rajeev Vibhakar, Christopher C Porter
Although some patients with acute leukemia have good prognoses, the prognosis of adult and pediatric patients who relapse or cannot tolerate standard chemotherapy is poor. Inhibition of WEE1 with AZD1775 has been shown to sensitize cancer cells to genotoxic chemotherapies including cytarabine in AML and T-ALL. Inhibition of WEE1 impairs homologous recombination by indirectly inhibiting BRCA2. Thus, we sought to determine if AZD1775 could sensitize cells to the PARP1/2 inhibitor olaparib. We found that combined treatment with AZD1775 and olaparib was synergistic in AML and ALL cells, and this combination impaired proliferative capacity upon drug withdrawal...
June 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28642445/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#11
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28642300/center-level-variation-in-accuracy-of-adverse-event-reporting-in-a-clinical-trial-for-pediatric-acute-myeloid-leukemia-a-report-from-the-children-s-oncology-group
#12
Tamara P Miller, Yimei Li, Marko Kavcic, Kelly D Getz, Yuan-Shun V Huang, Lillian Sung, Todd A Alonzo, Robert Gerbing, Marla H Daves, Terzah M Horton, Michael A Pulsipher, Jessica Pollard, Rochelle Bagatell, Alix E Seif, Brian T Fisher, Selina Luger, Alan S Gamis, Peter C Adamson, Richard Aplenc
No abstract text is available yet for this article.
June 22, 2017: Haematologica
https://www.readbyqxmd.com/read/28631293/region-dependent-patterns-of-trabecular-bone-growth-in-the-human-proximal-femur-a-study-of-3d-bone-microarchitecture-from-early-postnatal-to-late-childhood-period
#13
Petar Milovanovic, Danijela Djonic, Michael Hahn, Michael Amling, Björn Busse, Marija Djuric
OBJECTIVES: Parallel with body growth and development, bone structure in non-adults is reorganized to achieve the particular design observed in mature individuals. We traced the changes in three-dimensional trabecular microarchitectural design during the phases of locomotor maturation to clarify how human bone adapts to mechanical demands. MATERIALS AND METHODS: Micro-CT was performed on biomechanically-relevant subregions of the proximal femur (medial, intermediate and lateral neck regions, intertrochanteric region, metaphyseal region) from early postnatal period to late childhood...
June 20, 2017: American Journal of Physical Anthropology
https://www.readbyqxmd.com/read/28598536/characteristics-and-outcome-in-patients-with-central-nervous-system-involvement-treated-in-european-pediatric-acute-myeloid-leukemia-study-groups
#14
Ursula Creutzig, Michael N Dworzak, Martin Zimmermann, Dirk Reinhardt, Lucie Sramkova, Jan Pierre Bourquin, Henrik Hasle, Jonas Abrahamsson, Gertjan Kaspers, Mary M van den Heuvel, Ardine M J Reedijk, Barbara De Moerloose, Franco Locatelli, Riccardo Masetti
BACKGROUND: There is no consensus on the treatment for pediatric patients with acute myeloid leukemia and initial central nervous system (CNS) involvement. METHODS: To evaluate different CNS-directed treatment options (intrathecal [IT] therapy, CNS irradiation, hematopoietic stem cell transplantation [HSCT]), 261 patients (excluding acute promyelocytic leukemia) with initial CNS involvement treated in trials with similar intensive chemotherapy by four cooperative European study groups (1998-2013) were studied and compared with CNS-negative patients from the Berlin-Frankfurt-Münster group...
June 9, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28595195/gas6-oncogene-and-reverse-mllt3-kmt2a-duplications-in-an-infant-with-acute-myeloid-leukemia-and-a-novel-complex-hyperdiploid-karyotype-detailed-high-resolution-molecular-cytogenetic-studies
#15
Roberto R Capela de Matos, Daniela R Ney Garcia, Elaine Cifoni, Moneeb A K Othman, Mariana Tavares de Souza, Edna K Carboni, Gerson M Ferreira, Thomas Liehr, Raul C Ribeiro, Maria Luiza M Silva
Pediatric acute myeloid leukemia (AML) is a highly heterogeneous disease, presenting cytogenetic and molecular abnormalities which turned out to be critical prognostic factors. Ploidy changes as gain or loss of individual chromosomes are rare in AML, occurring only in about 1-2% of the affected children. Hyperdiploid karyotypes are exceedingly rare in infants less than 12 months of age. In this age group, structural rearrangements involving the KMT2A gene occur in about 58% of the cases. Among them, the translocation t(9;11)(p22;q23), KMT2A-MLLT3, is the most common abnormality accounting for approximately 22% of KMT2A rearrangements in infant AML cases...
June 9, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28584756/disseminated-cutaneous-trichosporonosis-in-an-adult-bone-marrow-transplant-patient
#16
A M Y Yong, S S Yang, K B Tan, S A Ho
The Trichosporon species are yeast-like opportunistic pathogens in immunocompromised patients. Trichosporon asahii infections have been reported in pediatric bone marrow transplant (BMT) patients. However, its incidence is low in the adult literature. A 52-year-old Chinese woman who was diagnosed with acute myeloid leukemia received induction chemotherapy and underwent allogenic bone marrow transplant, which was complicated by a relapse and required salvage chemotherapy. She developed persistent non-neutropenic fever secondary to presumed hepatosplenic candidiasis...
May 2017: Indian Dermatology Online Journal
https://www.readbyqxmd.com/read/28580501/predispositions-to-leukemia-in-down-syndrome-and-other-hereditary-disorders
#17
REVIEW
Satoshi Saida
Leukemia is the most common pediatric cancer and accounts for approximately one third of childhood malignancies. There are germline genetic alterations that significantly increase the risk of developing hematopoietic malignancies in childhood. In this review, we describe a number of these hereditary disorders and their clinical features. These predispositions to cancer syndromes can be attributed to DNA repair/genetic instability, RAS pathway dysfunction, bone marrow failure, telomeropathies, immunodeficiencies, transcription factor abnormalities, pure familial leukemia, and aneuploidy...
July 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28570300/impact-of-novel-polymorphisms-related-to-cytotoxicity-of-cytarabine-in-the-induction-treatment-of-acute-myeloid-leukemia
#18
Juan E Megías-Vericat, Pau Montesinos, María J Herrero, Federico Moscardó, Virginia Bosó, David Martínez-Cuadrón, José L Poveda, Miguel Á Sanz, Salvador F Aliño
Several novel single nucleotide polymorphisms (SNPs) involved in cytarabine cytotoxicity and related to clinical outcomes have been reported recently in a series of 232 pediatric patients with acute myeloid leukemia (AML). We report the first adult AML cohort in which the influence of these SNPs in cytarabine efficacy and toxicity was analyzed. Six of polymorphisms with clinical significance in the previous study [rs12036333, rs10758713, rs9883101, rs6550826, IRX2: rs2897047, mutated in colorectal cancers (MCC): rs7729269] were analyzed in a cohort of 225 adult patients at initial diagnosis of AML treated with an induction scheme of idarubicin plus cytarabine...
July 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28562519/epigenetic-combination-therapy-for-children-with-secondary-myelodysplastic-syndrome-mds-acute-myeloid-leukemia-aml-and-concurrent-solid-tumor-relapse
#19
Chana L Glasser, Alice Lee, Don Eslin, Lianna Marks, Shakeel Modak, Julia L Glade Bender
Secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) is a rare but devastating complication of solid tumor treatment involving high-dose topoisomerase II inhibitor and alkylator chemotherapy. For relapsed or elderly MDS and AML patients ineligible for hematopoietic stem cell transplantation, epigenetic therapies, including DNA methyltransferase inhibitors and histone deacetylase inhibitors, have been utilized as palliative therapy, offering a well-tolerated approach to disease stabilization, prolonged survival, and quality of life...
May 29, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28556917/decreased-relapsed-rate-and-treatment-related-mortality-contribute-to-improved-outcomes-for-pediatric-acute-myeloid-leukemia-in-successive-clinical-trials
#20
Thomas B Alexander, Lei Wang, Hiroto Inaba, Brandon M Triplett, Stanley Pounds, Raul C Ribeiro, Ching-Hon Pui, Jeffrey E Rubnitz
BACKGROUND: Outcomes for children with acute myeloid leukemia (AML) have improved over the past 20 years even though the medications used for induction therapy have not changed. METHODS: This study analyzed data from patients with AML who were enrolled in successive protocols (AML97 and AML02) to determine the contributors to the improved outcomes of the latter clinical trial. RESULTS: There were significant improvements in 5-year overall survival (48...
May 30, 2017: Cancer
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