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Leukemia Research

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https://www.readbyqxmd.com/read/28095351/level-of-granzyme-b-positive-t-regulatory-cells-is-a-strong-predictor-biomarker-of-acute-graft-versus-host-disease-after-day-30-after-allo-hsct
#1
Mikhail Y Drokov, Julia O Davydova, Larisa A Kuzmina, Irina V Galtseva, Nikolay M Kapranov, Vera A Vasilyeva, Darya S Dubnyak, Olga M Koroleva, Ekaterina D Mikhalcova, Natalia N Popova, Elena N Parovichnikova, Valery G Savchenko
Acute Graft-versus-host-disease (aGVHD), the major complication and one of the main causes of poor outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nowadays there are no widely accepted cell, plasma or another biomarker that can be used for aGVHD prediction. We hypothesized that a level of Granzyme B-positive T regulatory (GZMB-positive Treg) cells on day+30 after allo-HSCT could be the measure of immune response suppression and could predict aGVHD development after day +30. We applied a widespread and easy-to-perform method of multicolor flow cytometry to measure level of GZMB-positive Treg cells...
January 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28095352/the-relationship-of-rel-proto-oncogene-to-pathobiology-and-chemoresistance-in-follicular-and-transformed-follicular-lymphoma
#2
Xiaozhou Hu, Esra Baytak, Jinnan Li, Burcu Akman, Kaan Okay, Genfu Hu, Anna Scuto, Wenyan Zhang, Can Küçük
Follicular lymphoma (FL) is a common type of indolent lymphoma that occasionally transforms to more aggressive B-cell lymphomas. These transformed follicular lymphomas (tFL) are often associated with chemoresistance whose mechanisms are currently unknown. REL, a proto-oncogene located on frequently amplified 2p16.1-p15 locus, promotes tumorigenesis in many cancer types through deregulation of the NF-κB pathway; however, its role in FL pathobiology or chemoresistance has not been addressed. Here, we evaluated REL gene copy number by q-PCR on FFPE FL tumor samples, and observed REL amplification in 30...
January 9, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28088653/immune-stimulation-during-chemotherapy-increases-incidence-of-acute-graft-versus-host-disease-in-acute-myeloid-leukemia-a-study-on-behalf-of-sfgm-tc-and-alfa
#3
Lining Wang, Emmanuel Raffoux, Xavier Thomas, Ibrahim Yakoub-Agha, Jean-Henri Bouhris, Stéphane de Botton, Mauricette Michallet, Stéphanie Nguyen Quoc, Xavier Troussard, Eric Deconinck, Denis Caillot, Pascal Turlure, Stéphane Vigouroux, Arnaud Pigneux, Anne Huynh, Jean-Valère Malfuson, Michael Loschi, Gerard Socie, Hervé Dombret, Régis Peffault de la Tour, Thomas Cluzeau
60-70% of AML patients have an indication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) during their treatment. Graft versus host disease (GvHD), the major cause of mortality and comorbidities post-transplantation, develops by immunological mechanism and decides greatly prognosis and quality of life (QoL) of graft recipient. Current GvHD prophylaxis is not personalized. Infections, toxicities and leukemic infiltration complicate the first chemotherapy phases prior to allo-HSCT. They, to certain extent, induce local immune stimulation...
January 5, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28076835/the-functional-polymorphisms-of-lis1-are-associated-with-acute-myeloid-leukemia-risk-in-a-han-chinese-population
#4
Songyu Cao, Xiaomei Lu, Lihua Wang, Xifeng Qian, Guangfu Jin, Hongxia Ma
There is increasing evidence that the human lissencephaly-1 gene, LIS1, plays an important role in carcinogenesis of several malignancies including leukemia. However, little is known about the relationship between single nucleotide polymorphisms (SNPs) in LIS1 and the susceptibility to myeloid leukemia. In the present study, we systematically screened 5 potentially functional polymorphisms in LIS1, and conducted a case-control study including 660 acute myeloid leukemia (AML) patients and 1034 cancer-free controls in a Chinese population, to assess the association between these SNPs and AML risk...
January 2, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28092772/the-expression-of-endothelin-1-in-chronic-lymphocytic-leukemia-is-controlled-by-epigenetic-mechanisms-and-extracellular-stimuli
#5
Silvia Martinelli, Rossana Maffei, Stefania Fiorcari, Chiara Quadrelli, Patrizia Zucchini, Stefania Benatti, Leonardo Potenza, Mario Luppi, Roberto Marasca
Endothelin-1 (ET-1) is a hormone peptide widely expressed and is involved in several biological processes, important not only for normal cell function but also for tumor development, including cell proliferation, invasion, metastasis, angiogenesis and osteogenesis. In accordance, ET-1 was already shown to contribute to the growth and progression of many different solid cancers. We recently demonstrated that ET-1 has a role in the pathogenesis of chronic lymphocytic leukemia (CLL) where it is abnormally expressed...
December 30, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28063378/overexpression-of-ptp4a3-in-etv6-runx1-acute-lymphoblastic-leukemia
#6
Toni Grönroos, Susanna Teppo, Juha Mehtonen, Saara Laukkanen, Thomas Liuksiala, Matti Nykter, Merja Heinäniemi, Olli Lohi
Cell signalling, which is often derailed in cancer, is a network of multiple interconnected pathways with numerous feedback mechanisms. Dynamics of cell signalling is intimately regulated by addition and removal of phosphate groups by kinases and phosphatases. We examined expression of members of the PTP4A family of phosphatases across acute leukemias. While expression of PTP4A1 and PTP4A2 remained relatively unchanged across diseases, PTP4A3 showed marked overexpression in ETV6-RUNX1 and BCR-ABL1 subtypes of precursor B cell acute lymphoblastic leukemia...
December 26, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28056398/clinical-outcome-of-myeloid-sarcoma-in-adult-patients-and-effect-of-allogeneic-stem-cell-transplantation-results-from-a-multicenter-survey
#7
Davide Lazzarotto, Anna Candoni, Carla Filì, Fabio Forghieri, Livio Pagano, Alessandro Busca, Giuseppina Spinosa, Maria Elena Zannier, Erica Simeone, Miriam Isola, Erika Borlenghi, Lorella Melillo, Federico Mosna, Federica Lessi, Renato Fanin
INTRODUCTION: Myeloid Sarcoma (MS) is a rare hematologic myeloid neoplasm that can involve any site of the body. It can occur as an exclusively extramedullary form or it can be associated with an acute myeloid leukemia (AML), a chronic myeloproliferative neoplasm (MPN) or a myelodysplastic syndrome (MDS) at onset or at relapse. The rarity of MS does not enable prospective clinical trials and therefore a specific multicenter register can be useful for the clinical and biological studies of this rare disease...
December 20, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28033504/reduced-adamts-13-level-negatively-correlates-with-inflammation-factors-in-plasma-of-acute-myeloid-leukemia-patients
#8
Chen Liu, Lei Zhao, Jingzhong Zhao, Qinzhu Xu, Ying Song, Hui Wang
ADAMTS-13 is crucial for maintaining the normal size of vWF. Besides thrombotic thrombocytopenic purpura (TTP), decreased ADAMTS-13 had also been reported in patients with malignancy. However, the knowledge of expression and potential role of ADAMTS-13 in hematological malignancies is still limited. We measured and compared ADAMTS-13 levels in the plasma of 82 acute myeloid leukemia (AML) patients and 34 healthy controls and found that AML patients possessed lower ADAMTS-13 than controls. AML patients with infections possessed lower level of ADAMTS-13 than patients without infections and ADAMTS-13 levels were negatively correlated with C-reactive protein(CRP), IL-6, TNFα and IL-1β...
December 20, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28013106/cpx-351-exhibits-potent-and-direct-ex-vivo-cytotoxicity-against-aml-blasts-with-enhanced-efficacy-for-cells-harboring-the-flt3-itd-mutation
#9
Max J Gordon, Paul Tardi, Marc M Loriaux, Stephen E Spurgeon, Elie Traer, Tibor Kovacsovics, Lawrence D Mayer, Jeffrey W Tyner
PURPOSE: Identify AML patients most likely to respond to CPX-351, a nano-scale liposome formulation containing cytarabine and daunorubicin co-encapsulated at a 5:1 molar ratio. METHODS: We examined the ex vivo cytotoxic activity of CPX-351 against leukemic cells isolated from 53 AML patients and an additional 127 samples including acute lymphoblastic leukemia, myelodysplastic syndrome/myeloproliferative neoplasms, or chronic lymphocytic leukemia/lymphoma. We assessed activity with respect to common molecular lesions and used flow cytometry to assess CPX-351 cellular uptake...
December 12, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27978458/consolidation-with-autologous-stem-cell-transplantation-in-first-remission-is-safe-and-effective-in-aml-patients-above-65-years
#10
Alexander D Heini, Martin D Berger, Katja Seipel, Behrouz Mansouri Taleghani, Gabriela M Baerlocher, Kurt Leibundgut, Yara Banz, Urban Novak, Thomas Pabst
The outcome of AML patients ≥65 years remains disappointing. Current post-induction strategies for elderly AML patients fit for intensive treatment involve additional cycles of chemotherapy or allogeneic transplantation. Consolidation with autologous transplantation (ASCT) is poorly studied in these patients. In this single-center retrospective analysis, we determined survival rates of AML patients ≥65 years undergoing busulfan/cyclophosphamide conditioning before ASCT in first remission between 2007 and 2015...
December 8, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27951415/tetraploidy-near-tetraploidy-acute-myeloid-leukemia
#11
Lanshan Huang, Sa A Wang, Courtney DiNardo, Shaoying Li, Shimin Hu, Jie Xu, Wenli Zhou, Maitrayee Goswami, L Jeffrey Medeiros, Guilin Tang
A tetraploid/near tetraploid (T/NT) karyotype is a rare finding in acute myeloid leukemia (AML). Here we report 38 AML patients with a T/NT karyotype, including 26 men and 12 women with a median age of 65 years. T/NT karyotype was detected at initial diagnosis of AML in 16 patients, and acquired during the course of disease in 22 patients. All patients showed large blasts with frequent prominent nucleoli, cytoplasmic vacuoles and/or inclusions, nuclear irregularity and/or budding. Eleven patients had a non-complex and 27 had a complex T/NT karyotype; 21 patients also had pseudodiploid and/or triploid clones...
December 2, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27930945/a-phase-ii-study-of-panobinostat-in-patients-with-primary-myelofibrosis-pmf-and-post-polycythemia-vera-essential-thrombocythemia-myelofibrosis-post-pv-et-mf
#12
John Mascarenhas, Lonette Sandy, Min Lu, James Yoon, Bruce Petersen, David Zhang, Fei Ye, Carrie Newsom, Vesna Najfeld, Tsivia Hochman, Judith D Goldberg, Ronald Hoffman
Myelofibrosis is a chronic and progressive myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating symptoms and leukemic transformation. Ruxolitinib, an oral JAK1/2 inhibitor, is highly effective in ameliorating systemic symptoms and reducing splenomegaly. Current clinical research is focused on the evaluation of agents based on pre-clinical rationale that can result in disease course modification. Panobinostat is a pan-histone deacetylase inhibitor that has demonstrated clinical activity as a single agent in early phase trials of myelofibrosis...
November 30, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28038356/mrna-overexpression-of-the-hypoxia-inducible-factor-1-alpha-subunit-gene-hif1a-an-independent-predictor-of-poor-overall-survival-in-chronic-lymphocytic-leukemia
#13
Christos K Kontos, Sotirios G Papageorgiou, Marios A Diamantopoulos, Andreas Scorilas, Efthimia Bazani, Diamantina Vasilatou, Konstantinos Gkontopoulos, Eirini Glezou, Georgia Stavroulaki, George Dimitriadis, Vasiliki Pappa
The hypoxia inducible factor 1 (HIF1) is a heterodimeric transcription factor that ultimately regulates cellular responses to changes in oxygen tension. In this study, we examined the potential diagnostic and prognostic potential of the mRNA expression of HIF1 regulatory α-subunit (HIF1A) in chronic lymphocytic leukemia (CLL). For this purpose, total RNA was isolated from peripheral blood mononuclear cells collected from 88 CLL patients and 33 non-leukemic blood donors, and poly(A)-RNA was reversely transcribed...
November 29, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28024295/characterization-of-two-novel-fancg-mutations-in-indian-fanconi-anemia-patients
#14
Avani Solanki, C Kumar Selvaa, Frenny Sheth, Nita Radhakrishnan, Manas Kalra, Babu Rao Vundinti
FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. We have studied three patients clinically diagnosed as FA. All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c...
November 29, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28013105/the-effects-of-azacitidine-on-the-response-and-prognosis-of-myelodysplastic-syndrome-and-acute-myeloid-leukemia-involving-a-bone-marrow-erythroblast-frequency-of-50
#15
Tomoyuki Uchida, Masao Hagihara, Jian Hua, Morihiro Inoue
We reviewed the cases of 68 consecutive patients who were diagnosed with myelodysplastic syndrome (MDS, n=61) or acute erythroleukemia (AEL, n=7) according to the World Health Organization (WHO) 2008 criteria and had previously been treated with azacitidine, a hypomethylating agent. Fifteen MDS patients had bone marrow erythroblast frequencies of ≥50%, and 6 out of the 7 AEL patients were reclassified as MDS (refractory anemia with excess blasts [RAEB]-1: 1, RAEB-2: 5) according to the revised WHO 2016 criteria...
November 25, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27923195/aplastic-anemia-and-mds-international-foundation-aamdsif-bone-marrow-failure-disease-scientific-symposium-2016
#16
Amer M Zeidan, Minoo Battiwalla, Deborah Berlyne, Thomas Winkler
Patients with acquired and inherited bone marrow failure syndromes (BMFS) have ineffective hematopoiesis due to impairments of the hematopoietic stem cell compartment. Common manifestations of BMFS include varying degrees of peripheral blood cytopenias and, sometimes, progression to acute myelogenous leukemia. Research efforts have been made all over the world to improve understanding of the pathogenesis of these diseases and their clinical implications. The Aplastic Anemia and MDS International Foundation (AAMDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMFS...
November 24, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27930944/high-throughput-sequencing-in-acute-lymphoblastic-leukemia-follow-up-of-minimal-residual-disease-and-emergence-of-new-clones
#17
Mikaël Salson, Mathieu Giraud, Aurélie Caillault, Nathalie Grardel, Nicolas Duployez, Yann Ferret, Marc Duez, Ryan Herbert, Tatiana Rocher, Shéhérazade Sebda, Sabine Quief, Céline Villenet, Martin Figeac, Claude Preudhomme
Minimal residual disease (MRD) is known to be an independent prognostic factor in patients with acute lymphoblastic leukemia (ALL). High-throughput sequencing (HTS) is currently used in routine practice for the diagnosis and follow-up of patients with hematological neoplasms. In this retrospective study, we examined the role of immunoglobulin/T-cell receptor-based MRD in patients with ALL by HTS analysis of immunoglobulin H and/or T-cell receptor gamma chain loci in bone marrow samples from 11 patients with ALL, at diagnosis and during follow-up...
November 21, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27855324/green-tea-polyphenol-epigallocatechin-3-gallate-differentially-induces-apoptosis-in-cll-b-and-t-cells-but-not-in-healthy-b-and-t-cells-in-a-dose-dependant-manner
#18
Scott Cornwall, Gavin Cull, David Joske, Reza Ghassemifar
B-cell chronic lymphocytic leukaemia (CLL) is characterized by an accumulation of CD5-positive monoclonal B-cells due in large part to a failure of apoptosis. The ability to study CLL B-cells in vitro has always been a challenge and hampered by the low viability of the CLL B-cells in cell culture systems. In this study, we present a multicellular cell culture system to maintain CLL B-cells viable in culture for 60h in the presence of a stromal cell feeder layer in combination with a whole white blood cell preparation...
November 2, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27846431/increased-tim3-cd8-t-cells-in-myelodysplastic-syndrome-patients-displayed-less-perforin-and-granzyme-b-secretion-and-higher-cd95-expression
#19
Jinglian Tao, Lijuan Li, Yingshuai Wang, Rong Fu, Huaquan Wang, Zonghong Shao
T cell immunoglobulin and mucin domain 3(TIM3) is a negative regulator of cellular immunity and it is highly expressed on CD8+T cells in persistent viral infection and cancer setting as report. However, how TIM3 expressed on CD8+T cells in myelodysplastic syndrome (MDS), that is a malignant disorder, has not been clarified. Here, decreased CD8+T cells, less IFN-γ secretion in CD8+T cells and increased TIM3 on CD8+T cells had been seen. Increased TIM3+CD8+T cells with lower perforin and granzyme B expression and higher CD95 expression in MDS patients had been observed...
November 2, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27889686/microrna-181-contributes-to-downregulation-of-samhd1-expression-in-cd4-t-cells-derived-from-s%C3%A3-zary-syndrome-patients
#20
Rebecca Kohnken, Karthik M Kodigepalli, Anjali Mishra, Pierluigi Porcu, Li Wu
Sézary syndrome (SS) is a rare subtype of cutaneous T-cell lymphoma (CTCL) that is characterized by aggressive spread of neoplastic CD4+ T-cells from the skin into the bloodstream with metastasis to visceral organs. The deoxynucleoside triphosphohydrolase SAMHD1 is highly expressed in normal CD4+ T-cells, while its expression is down-regulated in CD4+ T-cells from SS patients. MicroRNA (miR) dysregulation is an important epigenetic mechanism in the pathogenesis and progression of SS. MiR-181 has been shown to inhibit SAMHD1 expression in cell lines and was identified as an important prognostic biomarker in CTCL...
January 2017: Leukemia Research
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