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Acute leukemias

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https://www.readbyqxmd.com/read/28535095/managing-cns-disease-in-adults-with-acute-lymphoblastic-leukemia
#1
Richard A Larson
The central nervous system (CNS) is an important site of involvement by acute lymphoblastic leukemia (ALL) in adults. The prevalence is sufficiently high that prophylactic treatment is routinely given to this sanctuary site in order to eradicate occult disease that might otherwise lead to a relapse. A lumbar puncture should be routinely performed in all newly diagnosed patients with ALL. The risks of CNS leukemia vary by phenotype and genotype. Preventive treatment of the CNS during post-remission therapy has become an integral part of all current ALL treatment protocols...
May 23, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28535084/impact-of-initial-csf-findings-on-outcome-among-patients-with-national-cancer-institute-standard-and-high-risk-b-cell-acute-lymphoblastic-leukemia-a-report-from-the-children-s-oncology-group
#2
Naomi Winick, Meenakshi Devidas, Si Chen, Kelly Maloney, Eric Larsen, Leonard Mattano, Michael J Borowitz, Andrew Carroll, Julie M Gastier-Foster, Nyla A Heerema, Cheryl Willman, Brent Wood, Mignon L Loh, Elizabeth Raetz, Stephen P Hunger, William L Carroll
Purpose To determine the prognostic significance of blasts, and of white and red blood cells, in CSF samples at diagnosis of acute lymphoblastic leukemia (ALL), a uniform CSF and risk group classification schema was incorporated into Children's Oncology Group B-cell ALL (B-ALL) clinical trials. Methods CSF status was designated as follows: CNS1, no blasts; CNS2a to 2c, < 5 WBCs/μL and blasts with/without ≥ 10 RBCs/μL or ≥ 5 WBCs/μL plus blasts, with WBCs ≥ 5 times the number of RBCs; CNS3a to 3c, ≥ 5 WBCs/μL plus blasts with/without ≥ 10 RBCs/μL or clinical signs of CNS disease...
May 23, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28534526/impact-of-genetic-polymorphisms-determining-leukocyte-neutrophil-count-on-chemotherapy-toxicity
#3
S J Glisovic, Y D Pastore, V Gagne, M Plesa, C Laverdière, J M Leclerc, D Sinnett, M Krajinovic
Neutropenia and infection are major dose-limiting side effects of chemotherapy. The risk of initial infection and subsequent complications are directly related to the depth and duration of neutropenia. Recent genome-wide association studies identified variants in DARC and CXCL2 genes, and in ORMDL3-GSDMA-CSF3 locus on chromosome 17q21 that influence white blood cell and neutrophil counts in healthy individuals. To investigate whether polymorphisms in these loci in conjunction with chemotherapy may modulate risk of treatment complications, we analyzed 21 SNPs across these genes for an association with chemotherapy-related neutropenia and infection in 286 Caucasian children with acute lymphoblastic leukemia...
May 23, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28534383/in-vitro-anticancer-activity-and-cytotoxicity-screening-of-phytochemical-extracts-from-selected-traditional-chinese-medicinal-plants
#4
Chao Liang, Hui Pan, Haizhou Li, Yang Zhao, Yang Feng
PURPOSE: The purpose of this study was to evaluate the anticancer activity of 10 selected traditional Chinese medicinal plants on 4 cancer cell lines, namely MCF-7 (breast carcinoma), BALL-1 (acute lymphoblastic leukemia), Huh-7 (hepatocellular carcinoma), HeLa (cervical carcinoma) and their cytotoxicity on a normal cell line, namely MCF-10A (non-tumorigenic mammary epithelial line), about which there were few reports previously. METHODS: Six phytochemical extracts, namely petroleum ether extract (PEE), chloroform extract (CE), ethyl acetate extract (EAE), n-butanol extract (BE), the remainder after extraction (RE) and water extract (WE) from each plant were prepared...
March 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28533941/changes-in-clinical-laboratory-parameters-and-pharmacodynamic-markers-in-response-to-blinatumomab-treatment-of-patients-with-relapsed-refractory-all
#5
Virginie Nägele, Andrea Kratzer, Gerhard Zugmaier, Chris Holland, Youssef Hijazi, Max S Topp, Nicola Gökbuget, Patrick A Baeuerle, Peter Kufer, Andreas Wolf, Matthias Klinger
BACKGROUND: Blinatumomab has shown a remission rate of 69% in an exploratory single-arm, phase II dose-escalation study in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We evaluated changes in laboratory parameters and immunopharmacodynamic markers in patients who received blinatumomab in the exploratory phase II study. METHODS: Data from 36 adults with relapsed/refractory ALL receiving blinatumomab as 4-week continuous IV infusions in various dose cohorts were analyzed for changes in liver enzymes, first-dose parameters, peripheral blood cell subpopulations, and cytokine/granzyme B release...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28533822/chemotherapy-induced-hypomethylation-of-n-myc-downstream-regulated-gene-4-in-the-bone-marrow-of-patients-with-acute-myeloid-leukemia
#6
Qingxiao Hong, Xiaoying Chen, Huadan Ye, Xiaodong Wu, Xuejing Wang, Lingyan Kong, Yongming Xia, Shiwei Duan
N-myc downstream-regulated gene 4 (NDRG4) has previously been investigated as a possible tumor suppressor. Hypermethylation of tumor suppressor genes contributes to the occurrence and development of certain types of cancer, including acute myeloid leukemia (AML). The current study aimed to assess the contribution of chemotherapy-induced NDRG4 changeable methylation to the development of AML. A total of 30 patients (13 males and 17 females) were involved in the present study. The DNA methylation levels of five C-phosphate-G sites of the NDRG4 gene were measured using bisulfite pyrosequencing techniques...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28533407/histone-binding-of-dpf2-mediates-its-repressive-role-in-myeloid-differentiation
#7
Ferdinand M Huber, Sarah M Greenblatt, Andrew M Davenport, Concepcion Martinez, Ye Xu, Ly P Vu, Stephen D Nimer, André Hoelz
Double plant homeodomain finger 2 (DPF2) is a highly evolutionarily conserved member of the d4 protein family that is ubiquitously expressed in human tissues and was recently shown to inhibit the myeloid differentiation of hematopoietic stem/progenitor and acute myelogenous leukemia cells. Here, we present the crystal structure of the tandem plant homeodomain finger domain of human DPF2 at 1.6-Å resolution. We show that DPF2 interacts with the acetylated tails of both histones 3 and 4 via bipartite binding pockets on the DPF2 surface...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533390/prognostic-and-biological-significance-of-the-proangiogenic-factor-egfl7-in-acute-myeloid-leukemia
#8
Dimitrios Papaioannou, Changxian Shen, Deedra Nicolet, Betina McNeil, Marius Bill, Malith Karunasiri, Matthew H Burke, Hatice Gulcin Ozer, Selen A Yilmaz, Nina Zitzer, Gregory K Behbehani, Christopher C Oakes, Damian J Steiner, Guido Marcucci, Bayard L Powell, Jonathan E Kolitz, Thomas H Carter, Eunice S Wang, Krzysztof Mrózek, Carlo M Croce, Michael A Caligiuri, Clara D Bloomfield, Ramiro Garzon, Adrienne M Dorrance
Epithelial growth factor-like 7 (EGFL7) is a protein that is secreted by endothelial cells and plays an important role in angiogenesis. Although EGFL7 is aberrantly overexpressed in solid tumors, its role in leukemia has not been evaluated. Here, we report that levels of both EGFL7 mRNA and EGFL7 protein are increased in blasts of patients with acute myeloid leukemia (AML) compared with normal bone marrow cells. High EGFL7 mRNA expression associates with lower complete remission rates, and shorter event-free and overall survival in older (age ≥60 y) and younger (age <60 y) patients with cytogenetically normal AML...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533192/in-vitro-effects-of-reprogramming-factors-on-the-expressions-of-pluripotent-genes-and-cd34-gene-in-human-acute-promyelocytic-leukemia-hl-60-cells
#9
Liang-Fang Zhu, Min Xiao, Yong-Quan Chen, Ling-Yan Wang, Xiao-Feng Luo, Xiao-Hong Yuan, Jin-Hua Ren, Zhi-Zhe Chen, Jian-Da Hu, Ting Yang
OBJECTIVE: Our study aims to explore the in vitro effects of reprogramming factors on the expressions of pluripotent genes and CD34 gene in HL-60 cells. METHODS: According to the construction of retroviral vector LV-OSCK of reprogramming factors (Oct-4, Sox2, Klf4, c-Myc), 293T cells were transfected to detect virus titer. The endogenous pluripotent genes (Oct4, SOX2, c-Myc and Klf4) and CD34 mRNA and protein expressions were detected by AP staining, immunofluorescence staining, qRT-PCR and flow cytometry...
May 19, 2017: Genomics
https://www.readbyqxmd.com/read/28533061/comparison-of-autologous-and-unrelated-transplants-for-cytogenetically-normal-acute-myeloid-leukemia
#10
Motonori Mizutani, Akiyoshi Takami, Masahiko Hara, Shohei Mizuno, Masamitsu Yanada, Takaaki Chou, Hitoji Uchiyama, Kazuteru Ohashi, Toshihiro Miyamoto, Yukiyasu Ozawa, Osamu Imataki, Naoki Kobayashi, Naoyuki Uchida, Heiwa Kanamori, Tomohiko Kamimura, Tetsuya Eto, Makoto Onizuka, Junji Tanaka, Yoshiko Atsuta, Shingo Yano
Allogeneic stem cell transplantation (SCT) from an HLA-matched sibling donor (MSD) is a post-remission treatment that offers a potential cure for adults with cytogenetically normal acute myeloid leukemia in their first complete remission (CN-AML/CR1). However, the best alternative in the absence of an MSD remains unclear. The aim of this study was to retrospectively compare the outcomes of autologous peripheral blood stem cell transplantation (auto-PBSCT; n = 177) to those of allogeneic bone marrow transplantation from an HLA-matched unrelated donor (MUD-BMT; n = 173) in adult patients with CN-AML/CR1...
May 19, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28532655/homozygous-tcf3-mutation-is-associated-with-severe-hypogammaglobulinemia-and-b-cell-acute-lymphoblastic-leukemia
#11
Meriem Ben-Ali, Jing Yang, Koon Wing Chan, Imen Ben-Mustapha, Najla Mekki, Chaouki Benabdesselem, Fethi Mellouli, Mohamed Bejaoui, WanLing Yang, Lamia Aissaoui, Yu Lung Lau, Mohamed-Ridha Barbouche
The identification of a homozygous TCF3 gene mutation in a patient presenting with severe hypogammaglobulinemia and acute lymphoblastic leukemia supports the crucial role of this transcription factor in normal B-lymphocyte development.
May 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28532177/targeting-non-hodgkin-lymphoma-with-blinatumomab
#12
Sheilagh Sanders, Douglas A Stewart
Management of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) remains challenging, and novel effective agents are eagerly awaited. Blinatumomab is a bispecific T-cell engager, targeting CD19. While blinatumomab's primary clinical use has been in B-cell acute lymphoblastic leukemia (B-ALL), there are increasing data for its use in B-lineage lymphomas. Areas covered: The aim of this review is to highlight the clinical data for blinatumomab use in NHL. Herein, the authors provide an overview of blinatumomab, its mechanism of action, its proven efficacy against B-ALL, and its phase I-II data assessing its use in NHL Expert opinion: Blinatumomab has modest activity in phase I-II trials in NHL, and may represent a means of bridging patients with relapsed disease to hematopoietic stem cell transplant...
May 22, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28530640/genetic-regulation-of-the-runx-transcription-factor-family-has-antitumor-effects
#13
Ken Morita, Kensho Suzuki, Shintaro Maeda, Akihiko Matsuo, Yoshihide Mitsuda, Chieko Tokushige, Gengo Kashiwazaki, Junichi Taniguchi, Rina Maeda, Mina Noura, Masahiro Hirata, Tatsuki Kataoka, Ayaka Yano, Yoshimi Yamada, Hiroki Kiyose, Mayu Tokumasu, Hidemasa Matsuo, Sunao Tanaka, Yasushi Okuno, Manabu Muto, Kazuhito Naka, Kosei Ito, Toshio Kitamura, Yasufumi Kaneda, Paul P Liu, Toshikazu Bando, Souichi Adachi, Hiroshi Sugiyama, Yasuhiko Kamikubo
Runt-related transcription factor 1 (RUNX1) is generally considered to function as a tumor suppressor in the development of leukemia, but a growing body of evidence suggests that it has pro-oncogenic properties in acute myeloid leukemia (AML). Here we have demonstrated that the antileukemic effect mediated by RUNX1 depletion is highly dependent on a functional p53-mediated cell death pathway. Increased expression of other RUNX family members, including RUNX2 and RUNX3, compensated for the antitumor effect elicited by RUNX1 silencing, and simultaneous attenuation of all RUNX family members as a cluster led to a much stronger antitumor effect relative to suppression of individual RUNX members...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28530458/-early-symptoms-of-childhood-malignant-diseases
#14
Zsuzsanna Erzsébet Papp, Izabella Kelemen, Adrienne Horváth
INTRODUCTION: Childhood malignant diseases are rare in pediatric pathology. Early symptoms are not specific, fatigue, pallor, compression signs and bone marrow failure are often mentioned. AIM: To summarize the most frequent early symptoms of childhood malignancies in order to help the physicians in the early recognition. METHOD: In our retrospective study, we processed a period of 5 years between 2012-2016, with an accent on the onset manifestations of malignancies...
May 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28529810/molecular-profiling-a-case-of-zbtb16-rara-acute-promyelocytic-leukemia
#15
Stephen E Langabeer, Lisa Preston, Johanna Kelly, Matt Goodyer, Ezzat Elhassadi, Amjad Hayat
Several variant RARA translocations have been reported in acute promyelocytic leukemia (APL) of which the t(11;17)(q23;q21), which results in a ZBTB16-RARA fusion, is the most widely identified and is largely resistant to therapy with all-trans retinoic acid (ATRA). The clinical course together with the cytogenetic and molecular characterization of a case of ATRA-unresponsive ZBTB16-RARA APL is described. Additional mutations potentially cooperating with the translocation fusion product in leukemogenesis have been hitherto unreported in ZBTB16-RARA APL and were sought by application of a next-generation sequencing approach to detect those recurrently found in myeloid malignancies...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28529314/a-critical-role-of-periostin-in-b-cell-acute-lymphoblastic-leukemia
#16
Z Ma, X Zhao, J Huang, X Jia, M Deng, D Cui, Z Du, G Fu, G Ouyang, C Xiao
Leukemia accepted article preview online, 22 May 2017. doi:10.1038/leu.2017.149.
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28529313/impact-of-killer-immunoglobulin-like-receptor-and-human-leukocyte-antigen-genotypes-on-the-efficacy-of-immunotherapy-in-acute-myeloid-leukemia
#17
E Bernson, A Hallner, F E Sander, O Wilsson, O Werlenius, A Rydström, R Kiffin, M Brune, R Foà, J Aurelius, A Martner, K Hellstrand, F B Thorén
Interactions between killer-immunoglobulin-like receptors (KIRs) and their HLA class I ligands are instrumental in natural killer (NK) cell regulation and protect normal tissue from NK cell attack. Human KIR haplotypes comprise genes encoding mainly inhibitory receptors (KIR A) or activating and inhibitory receptors (KIR B). A substantial fraction of humans lack ligands for inhibitory KIRs (iKIRs), i.e. a 'missing ligand' genotype. KIR B/x and missing ligand genotypes may thus give rise to potentially autoreactive, unlicensed NK cells...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28529312/prognostic-impact-of-ikzf1-deletions-in-association-with-vincristine-dexamethasone-pulses-during-maintenance-treatment-of-childhood-acute-lymphoblastic-leukemia-on-trial-all-bfm-95
#18
L Hinze, A Möricke, M Zimmermann, S Junk, G Cario, E Dagdan, C P Kratz, V Conter, M Schrappe, M Stanulla
Leukemia accepted article preview online, 22 May 2017. doi:10.1038/leu.2017.154.
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28528709/association-between-the-killer-cell-immunoglobulin-like-receptor-a-haplotype-and-childhood-acute-lymphoblastic-leukemia
#19
Awad E Osman, Abdullah Aljuryan, Hanan Al-Harthi, Mai Almeshari
Killer immunoglobulin-like receptors (KIRs) have the ability to regulate Natural killer (NK) cell function through inhibition/activation mechanisms. Healthy human cells express HLA class I ligands on their surface, which are recognized by NK cells to avoid spontaneous cell destruction. The associations of KIRs and/or HLA class 1 ligands in leukemic patients have been studied in some populations, with some of these studies demonstrating an association of specific types with leukemia. KIRs and their corresponding HLA class 1 ligands were investigated in Saudi patients with ALL and AML and compared to healthy controls...
May 18, 2017: Human Immunology
https://www.readbyqxmd.com/read/28528702/detailed-characterization-of-mesenchymal-stem-stromal-cells-from-a-large-cohort-of-aml-patients-demonstrates-a-definitive-link-to-treatment-outcomes
#20
Rafael Diaz de la Guardia, Belen Lopez-Millan, Jessie R Lavoie, Clara Bueno, Julio Castaño, Maite Gómez-Casares, Susana Vives, Laura Palomo, Manel Juan, Julio Delgado, Maria L Blanco, Josep Nomdedeu, Alberto Chaparro, Jose Luis Fuster, Eduardo Anguita, Michael Rosu-Myles, Pablo Menéndez
Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup...
May 18, 2017: Stem Cell Reports
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