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https://www.readbyqxmd.com/read/28108543/disease-characteristics-and-prognostic-implications-of-cell-surface-flt3-receptor-cd135-expression-in-pediatric-acute-myeloid-leukemia-a-report-from-the-children-s-oncology-group
#1
Katherine Tarlock, Todd A Alonzo, Michael R Loken, Robert B Gerbing, Rhonda E Ries, Richard Aplenc, Lillian Sung, Susana Raimondi, Betsy A Hirsch, Samir B Kahwash, Amy McKenney, E Anders Kolb, Alan S Gamis, Soheil Meshinchi
PURPOSE: The FLT3 cell-surface receptor tyrosine kinase (CD135) is expressed in a majority of both acute lymphoid leukemia (ALL) and myeloid leukemia (AML). However, the prognostic significance of CD135 expression in AML remains unclear. We therefore evaluated the association between FLT3 surface expression and disease characteristics and outcomes in pediatric patients with AML. EXPERIMENTAL DESIGN: We analyzed FLT3 receptor expression on AML blasts by multi-dimensional flow cytometry and its association with disease characteristics, clinical outcomes, and FLT3 transcript level in 367 children with AML treated on the Children's Oncology Group trial AAML0531...
January 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28108519/survival-of-acute-monocytic-leukemia-cells-is-driven-by-fatty-acid-oxidation-mediated-activation-of-ampk-in-bone-marrow-adipocytes
#2
Yoko Tabe, Shinichi Yamamoto, Kaori Saitoh, Kazumasa Sekihara, Norikazu Monma, Kazuho Ikeo, Kaoru Mogushi, Masato Shikami, Vivian R Ruvolo, Jo Ishizawa, Numsen Hail, Saiko Kazuno, Mamoru Igarashi, Hiromichi Matsushita, Yasunari Yamanaka, Hajime Arai, Isao Nagaoka, Takashi Miida, Yoshihide Hayashizaki, Marina Konopleva, Michael Andreeff
Leukemia cells in the bone marrow (BM) must meet the biochemical demands of increased cell proliferation by continually adapting to fluctuations in nutrient and oxygen availability. Thus, targeting metabolic abnormalities in leukemia cells located in the BM may provide an effective therapeutic strategy. In this study, we report the discovery of a metabolic role for BM adipocytes in supporting the growth of leukemic blasts. Preventing nutrient starvation-induced apoptosis of leukemic cells by BM adipocytes, as well as the metabolic and molecular mechanisms involved in this process, were investigated using various analytical techniques...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108507/flt3-and-jak2-mutations-in-acute-myeloid-leukemia-promote-inter-chromosomal-homologous-recombination-and-the-potential-for-copy-neutral-loss-of-heterozygosity-cn-loh
#3
Terry J Gaymes, Azim Mohamedali, Anthony Eiliazadeh, David Darling, Ghulam J Mufti
Acquired copy neutral loss-of-heterozygosity (CN-LOH) is a frequent occurrence in myeloid malignancies and is often associated with resistance to standard therapeutic modalities and poor survival. Here we show that constitutive signaling driven by mutated FLT3 and JAK2 confers inter-chromosomal homologous recombination (iHR), a precedent for CN-LOH. Using a targeted recombination assay, we determined significant iHR activity in internal tandem duplication FLT3 (FLT3-ITD) and JAK2V617F mutated cells. Sister chromatid exchanges, a surrogate measure of iHR, was significantly elevated in primary FLT3-ITD normal karyotype acute myeloid leukemia (NK-AML) compared to wild type FLT3 NK-AML...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108472/relapsed-acute-promyelocytic-leukemia-lacks-classic-leukemic-promyelocyte-morphology-and-can-create-diagnostic-challenges
#4
Vanessa J Dayton, Robert W McKenna, Sophia L Yohe, Michelle M Dolan, Elizabeth Courville, Harold Alvarez, Michael A Linden
OBJECTIVES: Although current therapies for acute promyelocytic leukemia (APL), such as all-trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. METHODS: By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review...
January 20, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28108471/prognostic-significance-of-residual-acute-myeloid-leukemia-in-bone-marrow-samples-taken-prior-to-allogeneic-hematopoietic-cell-transplantation
#5
Alexandra E Kovach, Andrew M Brunner, Amir T Fathi, Yi-Bin Chen, Robert P Hasserjian
OBJECTIVES: We sought to identify features in routine evaluation of pre-hematopoietic cell transplantation (HCT) bone marrow samples from patients with acute myeloid leukemia (AML) that influenced patient outcome. METHODS: Of 140 patients, evidence of residual leukemia (RL) was identified in 38 (27%) of pre-HCT samples, as defined by 5% or more aspirate blasts, increased blood blasts, clustered or necrotic blasts on biopsy specimens, and/or leukemia-associated karyotypic abnormalities...
January 20, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28108287/antitumor-activity-of-a-novel-and-orally-available-inhibitor-of-serine-palmitoyltransferase
#6
Masahiro Yaguchi, Sachio Shibata, Yoshinori Satomi, Megumi Hirayama, Ryutaro Adachi, Yasutomi Asano, Takuto Kojima, Yasuhiro Hirata, Akio Mizutani, Atsushi Kiba, Yoji Sagiya
Metabolic reprogramming is an essential hallmark of neoplasia. Therefore, targeting cancer metabolism, including lipid synthesis, has attracted much interest in recent years. Serine palmitoyltransferase (SPT) plays a key role in the initial and rate-limiting step of de novo sphingolipid biosynthesis, and inhibiting SPT activity prevents the proliferation of certain cancer cells. Here, we identified a novel and orally available SPT inhibitor, compound-2. Compound-2 showed an anti-proliferative effect in several cancer cell models, reducing the levels of the sphingolipids ceramide and sphingomyelin...
January 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28108271/comparative-effectiveness-of-busulfan-and-fludarabine-versus-fludarabine-and-400-cgy-total-body-irradiation-conditioning-regimens-for-aml-mds
#7
Moaath Mustafa Ali, Donna M Abounader, Lisa A Rybicki, Melissa A Yurch, Jamie Starn, Christina Ferraro, Victoria Winslow, Betty K Hamilton, Aaron T Gerds, Hien Liu, Robert Dean, Brian T Hill, Brad Pohlman, Steven Andresen, Rabi Hanna, Matt Kalaycio, Brian J Bolwell, Navneet S Majhail, Ronald Sobecks
Allogeneic hematopoietic cell transplantation (alloHCT) conditioning regimen intensity has varied for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). A comparative effectiveness analysis was performed to assess outcomes of busulfan and fludarabine (BuFlu) versus fludarabine and 400 cGy total body irradiation (FluTBI) conditioning. Thirty-three subjects received BuFlu and 38 had FluTBI. The BuFlu group received more red blood cell transfusions (P=0.02) and had a longer time to platelet recovery (P=0...
January 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28108116/maternal-exposure-to-ambient-air-pollution-and-risk-of-early-childhood-cancers-a-population-based-study-in-ontario-canada
#8
Éric Lavigne, Marc-André Bélair, Minh T Do, David M Stieb, Perry Hystad, Aaron van Donkelaar, Randall V Martin, Daniel L Crouse, Eric Crighton, Hong Chen, Jeffrey R Brook, Richard T Burnett, Scott Weichenthal, Paul J Villeneuve, Teresa To, Sabit Cakmak, Markey Johnson, Abdool S Yasseen, Kenneth C Johnson, Marianna Ofner, Lin Xie, Mark Walker
BACKGROUND: There are increasing concerns regarding the role of exposure to ambient air pollution during pregnancy in the development of early childhood cancers. OBJECTIVE: This population based study examined whether prenatal and early life (<1year of age) exposures to ambient air pollutants, including nitrogen dioxide (NO2) and particulate matter with aerodynamic diameters ≤2.5μm (PM2.5), were associated with selected common early childhood cancers in Canada...
January 17, 2017: Environment International
https://www.readbyqxmd.com/read/28107692/rna-binding-protein-msi2-positively-regulates-flt3-expression-in-myeloid-leukemia
#9
Ayuna Hattori, Daniel McSkimming, Natarajan Kannan, Takahiro Ito
FLT3 is frequently mutated and overexpressed in acute myelogenous leukemia (AML) and other hematologic malignancies. Although signaling events downstream of FLT3 receptor tyrosine kinase has been studied in depth, molecular mechanisms of how FLT3 expression is regulated at the post-transcriptional level in particular remain elusive. In this study, we investigated the roles of an RNA binding protein MSI2 as a regulator of FLT3 expression. MSI2 and FLT3 are significantly co-regulated in human AML and chronic myelogenous leukemia in blast crisis (BC-CML)...
January 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28107581/mir-9-plays-a-role-in-il-10-mediated-expression-of-e-cadherin-in-acute-myelogenous-leukemia-cells
#10
Chie Nishioka, Takayuki Ikezoe, Bin Pan, Kailin Xu, Akihito Yokoyama
We previously showed that the CD82/STAT5/IL-10 axis is activated in CD34(+) /CD38(-) acute myelogenous leukemia (AML) cells which favor bone marrow microenvironment. The present study explored the novel biological function of IL-10 in regulation of expression of adhesion molecules in AML cells and found that exposing AML cells to IL-10 induced expression of E-cadherin, but not other adhesion molecules including VLA4, CD29, and LFA1. Downregulation of E-cadherin with a small interfering RNA (siRNA) suppressed the adhesion of leukemia cells to bone marrow-derived mesenchymal stem cells and enhanced the anti-leukemia effect of cytarabine (AraC)...
January 20, 2017: Cancer Science
https://www.readbyqxmd.com/read/28107040/effects-of-malnutrition-on-neutrophil-mononuclear-cell-apoptotic-functions-in-children-with-acute-lymphoblastic-leukemia
#11
Fatma Betul Cakir, Su Gülsün Berrak, Gonul Aydogan, Aysin Tulunay, Cetin Timur, Cengiz Canpolat, Emel Eksioglu Demiralp
BACKGROUND: Recent studies claim that apoptosis may explain immune dysfunction observed in malnutrition. OBJECTIVE: The objective of this study was to determine the effect of malnutrition on apoptotic functions of phagocytic cells in acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Twenty-eight ALL patients (13 with malnutrition) and thirty controls were enrolled. Neutrophil and mononuclear cell apoptosis of ALL patients and the control group were studied on admission before chemotherapy and repeated at a minimum of three months after induction of chemotherapy or when the nutritional status of leukemic children improved...
January 20, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28106878/late-effects-in-survivors-of-infantile-acute-leukemia-a-study-of-the-l-e-a-program
#12
V Gandemer, J Bonneau, C Oudin, J Berbis, Y Bertrand, M-D Tabone, S Ducassou, P Chastagner, B Brethon, J-H Dalle, S Thouvenin, M Poiree, D Plantaz, J Kanold, N Sirvent, P Lutz, Z Hamidou, A Baruchel, G Leverger, P Auquier, G Michel
No abstract text is available yet for this article.
January 20, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28106537/down-regulation-of-pseudogene-vimentin-2p-is-associated-with-poor-outcome-in-de-novo-acute-myeloid-leukemia
#13
Ling-Ling Zhai, Jiao Zhou, Jing Zhang, Xi Tang, Ling-Yu Zhou, Jia-Yu Yin, Minse-Evola Deniz Vanessa, Wen Peng, Jiang Lin, Zhao-Qun Deng
OBJECTIVES: This study was intended to investigate the expression status of Vimentin 2p (VIM 2p), a pseudogene of Vimentin, and further analyze its clinical significance in AML patients. METHODS: Real-time quantitative PCR (RQ-PCR) was employed to explore the expression status of VIM 2p in 128 patients with de novo AML and 36 healthy controls. RESULTS: The expression level of VIM 2p was significantly decreased compared with healthy controls (P< 0...
January 13, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28106288/nuclear-inositide-signaling-via-phospholipase-c
#14
Stefano Ratti, Sara Mongiorgi, Giulia Ramazzotti, Matilde Y Follo, Giulia A Mariani, Pann-Ghill Suh, James A McCubrey, Lucio Cocco, Lucia Manzoli
The existence of an independent nuclear inositide pathway distinct from the cytoplasmic one has been demonstrated in different physiological systems and in diseases. In this prospect we analyze the role of PI-PLCβ1 nuclear isoform in relation to the cell cycle regulation, the cell differentiation and different physiopathological pathways focusing on the importance of the nuclear localization from both molecular and clinical point of view. PI-PLCβ1 is essential for G1/S transition through DAG and Cyclin D3 and plays also a central role in G2/M progression through Cyclin B1 and PKCα...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28105492/acute-leukemias-xvi
#15
(no author information available yet)
No abstract text is available yet for this article.
January 20, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28105353/isolated-extramedullary-cutaneous-relapse-despite-concomitant-severe-graft-vs-host-disease-and-tissue-chimerism-analysis-in-a-patient-with-acute-lymphoblastic-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation-a-case-report
#16
Bulent Kantarcioglu, Huseyin Saffet Bekoz, Yeliz Duvarci Ogret, Asli Cakir, Demet Kivanc, Fatma Savran Oguz, Deniz Sargin
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with acute lymphoblastic leukemia (ALL). The curative potential of allo-HSCT for ALL is, in part, due to the graft-vs.-leukemia (GVL) effect, in addition to the intensive conditioning chemo-radiotherapy. However, relapse remains the major cause of treatment failure following allo-HSCT for ALL. In the allo-HSCT setting, testing for genetic markers of hematopoietic chimerism has become a part of the routine diagnostic program...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28104920/clinical-utility-of-gene-panel-based-testing-for-hereditary-myelodysplastic-syndrome-acute-leukemia-predisposition-syndromes
#17
L Guidugli, A K Johnson, G Alkorta-Aranburu, V Nelakuditi, K Arndt, J E Churpek, L A Godley, D Townsley, N S Young, C Fitzpatrick, D Del Gaudio, S Das, Z Li
Leukemia accepted article preview online, 20 January 2017. doi:10.1038/leu.2017.28.
January 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28104648/identification-of-merkel-cell-polyomavirus-from-a-patient-with-acute-myeloid-leukemia
#18
Y Song, P Gyarmati
Merkel cell polyomavirus (MCPyV) is an oncogenic virus associated with Merkel cell carcinoma, an aggressive form of skin cancer with a high (>30%) mortality rate. The virus has a high incidence in patients with immunosuppressed conditions, such as AIDS or leukemia, or following organ transplantation. Here, we report the complete genomic sequence of MCPyV identified from a blood sample from a patient with acute myeloid leukemia.
January 19, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28103944/a-comparison-between-allogeneic-stem-cell-transplantation-from-unmanipulated-haploidentical-and-unrelated-donors-in-acute-leukemia
#19
Simona Piemontese, F Ciceri, M Labopin, W Arcese, S Kyrcz-Krzemien, S Santarone, H Huang, D Beelen, N C Gorin, C Craddock, Z Gulbas, A Bacigalupo, M Mohty, A Nagler
BACKGROUND: In the absence of a HLA-matched related or matched unrelated donor, allogeneic stem cell transplantation (allo-SCT) from mismatched unrelated donors or haploidentical donors are potential alternatives for patients with acute leukemia with an indication to allo-SCT. The objective of this study was to compare the outcome of allo-SCT from T cell-replete haploidentical (Haplo) versus matched (MUD 10/10) or mismatched unrelated donor at a single HLA-locus (MMUD 9/10) for patients with acute leukemia in remission...
January 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28103640/addition-of-cladribine-to-the-standard-induction-treatment-improves-outcomes-in-a-subset-of-elderly-aml-patients-results-of-a-randomized-polish-adult-leukemia-group-palg-phase-ii-trial
#20
Agnieszka Pluta, Tadeusz Robak, Agata Wrzesien-Kus, Bozena Katarzyna Budziszewska, Kazimierz Sulek, Ewa Wawrzyniak, Magdalena Czemerska, Malgorzata Zwolinska, Aleksandra Golos, Aleksandra Holowiecka-Goral, Slawomira Kyrcz-Krzemien, Jaroslaw Piszcz, Janusz Kloczko, Monika Mordak-Domagala, Andrzej Lange, Małgorzata Razny, Krzysztof Madry, Wieslaw Wiktor-Jedrzejczak, Sebastian Grosicki, Aleksandra Butrym, Kazimierz Kuliczkowski, Krzysztof Warzocha, Jerzy Holowiecki, Sebastian Giebel, Richard Szydlo, Agnieszka Wierzbowska
Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients, the present randomized phase II study compares efficacy and toxicity of the DAC (daunorubicin plus cytarabine plus cladribine) regimen with the standard DA (daunorubicin plus cytarabine) regimen in the newly diagnosed AML patients over 60 years of age...
January 19, 2017: American Journal of Hematology
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