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Leukemia Research

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https://www.readbyqxmd.com/read/28934679/the-kinetics-of-white-blood-cell-and-the-predictive-factors-of-leukocytosis-under-oral-or-intravenous-arsenic-as-the-first-line-treatment-for-acute-promyelocytic-leukemia
#1
Fang Wang, Jin-Song Jia, Jing Wang, Ting Zhao, Qian Jiang, Hao Jiang, Hong-Hu Zhu
OBJECTIVE: We aimed to compare the kinetics of white blood cell (WBC) and explore predictive factors of leukocytosis in non-high-risk acute promyelocytic leukemia (APL), with oral arsenic plus all-trans retinoic acid (ATRA) or intravenous arsenic trioxide (ATO) plus ATRA as a first-line treatment. METHODS: The absolute count, doubling time and peak time of WBC were analyzed in 64 newly diagnosed non-high-risk APL patients who were treated with different induction regimens containing either oral Realgar-indigo naturalis formula (RIF) (n=35) or ATO (n=29)...
September 14, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28934678/establishment-of-cell-line-with-nk-nkt-phenotype-from-myeloid-nk-cell-acute-leukemia
#2
A Darji, N Desai, R Modi, B Khamar, S Rajkumar
Acute Myeloid Leukemia (AML) is the most common malignancy in adults with a 5-year survival rate of 27% of the total affected population. For effective treatment and new drug discovery, cell lines are considered as a very important tool. Here we report an establishment of a continuous human cell line AML-004 with a hypo-diploid chromosome 44 and presence of both NK/NKT phenotypes. The cell line was isolated from the blood sample of myeloid NK cell acute leukemia patients and extensively characterized by flow cytometery, morphology, and cytogentic analysis...
September 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28917156/tgf%C3%AE-1-synergizes-with-flt3-ligand-to-induce-chemoresistant-quiescence-in-acute-lymphoblastic-leukemia-with-mll-gene-rearrangements
#3
M Tamai, Y Furuichi, S Kasai, N Ando, D Harama, K Goi, T Inukai, K Kagami, M Abe, H Ichikawa, K Sugita
Fms-like tyrosine kinase 3 (FLT3) is highly expressed in mixed-lineage leukemia (MLL) gene-rearranged acute lymphoblastic leukemia (MLL+ALL) with a dismal prognosis. We previously reported that FLT3 ligand (FL) stimulation induced cell cycle arrest in MLL+ALL cells leading to resistance against anti-leukemic agents. Given that FL stimulation enhanced transforming growth factor (TGF)β1 mRNA levels in MLL+ALL cells, we extensively examined the effect of TGFβ1 on the cell cycle progression and chemosensitivity in MLL+ALL cells, and found that TGFβ1 stimulation induced MLL+ALL cells into cell cycle arrest resistant to arabinosyl cytosine; its effect was markedly enhanced in synergy with FL...
September 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28942350/refractory-macrocytic-anemias-in-patients-with-clonal-hematopoietic-disorders-and-isolated-mutations-of-the-spliceosome-gene-zrsr2
#4
Roger A Fleischman, Shannon S Stockton, Christopher R Cogle
Although mutations in RNA splicing genes occur frequently in patients with clonal cytopenias of unknown significance (CCUS) and myelodysplastic syndromes (MDS), very often additional common myeloid gene driver mutations are present at diagnosis. Thus, the clinical significance of isolated mutations in the most commonly mutated RNA splicing genes remains unknown. Here we report five unusual patients with an isolated mutation causing a loss of function of ZRSR2, a protein required for recognition of a functional 3' splice site...
September 8, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28938223/the-high-frequency-of-the-u2af1-s34y-mutation-and-its-association-with-isolated-trisomy-8-in-myelodysplastic-syndrome-in-asians-but-not-in-caucasians
#5
Seon Young Kim, Kwantae Kim, Byungjin Hwang, Kyongok Im, Si Nae Park, Jung-Ah Kim, Sang Mee Hwang, Duhee Bang, Dong Soon Lee
Mutational profiles of 153 Korean myelodysplastic syndrome (MDS) patients were investigated. Sequencing of 87 genes presented similar mutational profiles in Korean MDS patients compared with previous reports. The most frequently mutated genes were ASXL1 (22.9%), U2AF1 (16.3%), TP53 (13.7%), RUNX1 (10.5%), TET2 (10.5%), DNMT3A (8.5%), and SRSF2 (8.5%). The U2AF1 mutation frequency was higher, with different frequencies in the mutated sites of U2AF1 (S34Y, 6/25; S34F, 11/25; and Q157P 8/25). The U2AF1 S34Y mutation was strongly associated with isolated trisomy 8 (5/6, 83%) and was characterized by a younger age of MDS onset (median, 39 years)...
September 7, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28934680/a-phase-1-study-of-the-janus-kinase-2-jak2-v617f-inhibitor-gandotinib-ly2784544-in-patients-with-primary-myelofibrosis-polycythemia-vera-and-essential-thrombocythemia
#6
Srdan Verstovsek, Ruben A Mesa, Mohamed E Salama, Li Li, Celine Pitou, Fabio P Nunes, Gregory L Price, Jennifer L Giles, Deborah N D'Souza, Richard A Walgren, Josef T Prchal
Mutations in Janus kinase 2 (JAK2) are implicated in the pathogenesis of Philadelphia-chromosome negative myeloproliferative neoplasms, including primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Gandotinib (LY2784544), a potent inhibitor of JAK2 activity, shows increased potency for the JAK2(V617F) mutation. The study had a standard 3+3 dose-escalation design to define the maximum-tolerated dose. Primary objectives were to determine safety, tolerability, and recommended oral daily dose of gandotinib for patients with JAK2(V617F)-positive myelofibrosis, essential thrombocythemia, or polycythemia vera...
August 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28888102/a-new-mechanism-of-resistance-to-abl1-tyrosine-kinase-inhibitors-in-a-bcr-abl1-positive-cell-line
#7
Kelly Airiau, Béatrice Turcq, François-Xavier Mahon, Francis Belloc
Tyrosine kinase inhibitors (TKI) constitute the frontline treatment for chronic myeloid leukemia patients. Dasatinib, a second-generation TKI, was developed to overcome TKI resistances. However, dasatinib resistances are also described but remain less characterized. To mimic in vivo acquired dasatinib resistance, the BCR-ABL1-positive cell line K562 was transiently treated with a pharmacological concentration of dasatinib, for a short time in the presence of stem cell factor. A dasatinib resistant counterpart (K562 RES) was developed...
August 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28910610/platelet-transfusion-refractoriness-in-patients-with-acute-myeloid-leukemia-treated-by-intensive-chemotherapy
#8
Thibault Comont, Suzanne Tavitian, Laurent Bardiaux, Marylise Fort, Bénédicte Debiol, Danièle Morère, Emilie Bérard, Eric Delabesse, Isabelle Luquet, Salima Martinez, Françoise Huguet, Christian Récher, Sarah Bertoli
Platelet transfusion refractoriness (PTR) is a major adverse event in the management of acute myeloid leukemia (AML). In a series of 897 adult patients with AML receiving intensive chemotherapy, we identified 41 patients (4.8%) with PTR. PTR was more frequently observed in parous women, patients with extra-medullary disease, a low white blood cell count, an infection, or hemophagocytic syndrome. Among the 31 patients with anti-human leucocyte antigen (HLA) antibodies, an HLA-matched donor was identified for 18 patients (58...
August 30, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28869817/dna-hypermethylation-of-tumor-suppressor-genes-rassf6-and-rassf10-as-independent-prognostic-factors-in-adult-acute-lymphoblastic-leukemia
#9
Samareh Younesian, Sepideh Shahkarami, Parisa Ghaffari, Shaban Alizadeh, Roya Mehrasa, Ardeshir Ghavamzadeh, Seyed H Ghaffari
BACKGROUND: The Hypermethylation of Ras association domain family (RASSF) often plays a key role in malignant progression of solid tumors; however, their impact on the prognosis and survival of adult ALL patients remain elusive. METHODS: The frequency of the promoter methylation pattern of RASSF6 and RASSF10 were analyzed in the peripheral blood (PB) samples taken at the time of diagnosis of 45 ALL patients. The methylation-specific PCR (MSP) assay was used to detect the DNA methylation patterns...
August 30, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28869816/timed-sequential-therapy-for-acute-myelogenous-leukemia-results-of-a-retrospective-study-of-301-patients-and-review-of-the-literature
#10
Kelly J Norsworthy, Amy E DeZern, Hua-Ling Tsai, Wesley A Hand, Ravi Varadhan, Steven D Gore, Ivana Gojo, Keith Pratz, Hetty E Carraway, Margaret Showel, Michael A McDevitt, Douglas Gladstone, Gabriel Ghiaur, Gabrielle Prince, Amy H Seung, Dina Benani, Mark J Levis, Judith E Karp, B Douglas Smith
Timed sequential therapy (TST) aims to improve outcomes in acute myelogenous leukemia (AML) by harnessing drug-induced cell cycle kinetics of AML, where a second drug is timed to coincide with peak leukemia proliferation induced by the first drugs. We analyzed outcomes in 301 newly diagnosed AML patients treated from 2004-2013 with cytarabine, anthracycline, and etoposide TST induction. Median age was 52 (range 20-74) and complete remission rate 68%. With median follow-up 5.8 years, 5-year DFS and overall survival (OS) were 37% (95% CI 31-45%) and 32% (95% CI 27-38%), respectively...
August 30, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28892661/inhibition-of-c-rel-using-sirna-increased-apoptosis-and-decreased-proliferation-in-pre-b-all-blasts-therapeutic-implications
#11
Seyedeh Momeneh Mohammadi, Daryosh Mohammadnejad, Abbas Ali Hosseinpour Feizi, Ali Akbar Movassaghpour, Soheila Montazersaheb, Hojjatollah Nozad Charoudeh
The c-Rel transcription factor is a unique member of the NF-kB family that has a role in apoptosis, proliferation and cell survival. Overexpression of c-Rel is detected in many human B cell tumors, including B-cell leukemia and several cancers. The study aimed to investigate the effects of c-Rel siRNA on the proliferation and apoptosis of relapsed pre-B acute leukemia cells. The c-Rel siRNA was transfected into Leukemia cells using an Amaxa cell line Nucleofector kit L (Lonza). Quantitative real-time RT-PCR (qRT-PCR) and western blot were done to measure the expression levels of mRNA and protein, respectively...
August 26, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28886412/re-evaluation-of-acute-erythroid-leukemia-according-to-the-2016-who-classification
#12
Yan Chen, Maryam Pourabdollah, Eshetu G Atenafu, Anne Tierens, Aaron Schimmer, Hong Chang
In the recent update of WHO classification, the definition of myeloid neoplasms with erythroid predominance has been modified shifting the main criteria for calculating blast percentage from non-erythroid cells (NEC) to all nucleated marrow cells (ANC). Thus, the cases previously classified as erythroid/myeloid subtype of acute erythroid leukemia (AEL) based on the 2008 WHO will now be categorized either as myelodysplastic syndrome with excess blasts (MDS-EB) or acute myeloid leukemia, not otherwise specified (AML-NOS)...
August 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28846953/post-remissional-and-pre-transplant-role-of-minimal-residual-disease-detected-by-wt1-in-acute-myeloid-leukemia-a-retrospective-cohort-study
#13
Chiara Frairia, Semra Aydin, Ernesta Audisio, Ludovica Riera, Sabrina Aliberti, Bernardino Allione, Alessandro Busca, Stefano D'Ardia, Chiara Maria Dellacasa, Anna Demurtas, Andrea Evangelista, Giovannino Ciccone, Paola Francia di Celle, Barbara Nicolino, Alessandra Stacchini, Filippo Marmont, Umberto Vitolo
In acute myeloid leukemia (AML), the detection of minimal residual disease (MRD) is still under investigation. The aim of the present retrospective study was to assess the role of Wilms tumor gene 1 (WT1) overexpression in a large monocentric cohort of AML patients. Among 255 enrolled patients, MRD was investigated in those in complete remission (CR) with an available WT1 at baseline (>250 copies) and at two further time-points: after induction (n=117) and prior allogeneic hematopoietic cell transplantation (allo-HCT), n=65...
August 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28866351/human-t-cell-leukemia-virus-type-i-tax-genotype-analysis-in-okinawa-the-southernmost-and-remotest-islands-of-japan-different-distributions-compared-with-mainland-japan-and-the-potential-value-for-the-prognosis-of-aggressive-adult-t-cell-leukemia-lymphoma
#14
Shugo Sakihama, Mineki Saito, Megumi Kuba-Miyara, Takeaki Tomoyose, Naoya Taira, Takashi Miyagi, Masaki Hayashi, Shigeko Kinjo, Sawako Nakachi, Iori Tedokon, Yukiko Nishi, Keita Tamaki, Kazuho Morichika, Jun-Nosuke Uchihara, Satoko Morishima, Ken-Nosuke Karube, Yuetsu Tanaka, Hiroaki Masuzaki, Takuya Fukushima
Okinawa, comprising remote islands off the mainland of Japan, is an endemic area of human T-cell leukemia virus type I (HTLV-1), the causative virus of adult T-cell leukemia-lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). We investigated the tax genotype of HTLV-1 among 29 HTLV-1 carriers, 74 ATL patients, and 33 HAM patients in Okinawa. The genotype distribution-60 (44%) taxA cases and 76 (56%) taxB cases-differed from that of a previous report from Kagoshima Prefecture in mainland Japan (taxA, 10%; taxB, 90%)...
August 18, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28841441/hla-g-molecules-and-clinical-outcome-in-chronic-myeloid-leukemia
#15
Giovanni Caocci, Marianna Greco, Marcella Arras, Roberto Cusano, Sandro Orrù, Bruno Martino, Elisabetta Abruzzese, Sara Galimberti, Olga Mulas, Marcello Trucas, Roberto Littera, Sara Lai, Carlo Carcassi, Giorgio La Nasa
The human leukocyte antigen-G (HLA-G) gene encodes a tolerogenic protein known to promote tumor immune-escape. We investigated HLA-G polymorphisms and soluble molecules (sHLA-G) in 68 chronic myeloid leukemia (CML) patients. Patients with G*01:01:01 or G*01:01:02 allele had higher value of sHLA-G compared to G*01:01:03 (109.2±39.5 vs 39.9±8.8 units/ml; p=0.03), and showed lower event free survival (EFS) (62.3% vs 90.0%; p=0.02). The G*01:01:03 allele was associated with higher rates and earlier achievement of deep molecular response (MR)(4...
August 18, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28843161/ruxolitinib-for-the-management-of-myelofibrosis-results-of-an-international-physician-survey
#16
Martin H Ellis, Maya Koren-Michowitz, Noa Lavi, Alessandro M Vannucchi, Ruben Mesa, Claire N Harrison
BACKGROUND: Ruxolitinib is established as treatment for symptomatic myeloproliferative neoplasm (MPN)-associated myelofibrosis. The strict inclusion and exclusion criteria and dose modification rules that applied to the COMFORTI and II studies that led to the licensing of ruxolitinib are not always applicable to routine clinical practice. Thus physicians now face decisions regarding ruxolitinib use that were not addressed in these pivotal trials. METHODS: We performed an online survey of hematologists practicing in Europe, Israel, the United Kingdom and the United States...
August 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28818808/potent-induction-of-apoptosis-by-givinostat-in-bcr-abl1-positive-and-bcr-abl1-negative-precursor-b-cell-acute-lymphoblastic-leukemia-cell-lines
#17
Chenjiao Yao, Guojuan Zhang, Alison Walker, Kevin Y Zhao, Ying Li, Lei Lyu, Yan Tang, Peng Ru, Dan Jones, Weiqiang Zhao
We have previously shown that givinostat can induce potent apoptosis in the BCR-ABL1-positive, TP53-wild type B-cell acute lymphoblastic leukemia (B-ALL) cell line SUP-B15. We extend our studies here to two additional B-ALL cell lines, BCR-ABL1-negative CCRF-SB and p210 BCR-ABL1-positive NAML1. Givinostat induced significant cell growth inhibition in both cell lines, with an IC50 of 0.65±0.052μM and 0.25±0.028μM in CCRF-SB and NAML1, respectively. The key signal protein of the BCR-ABL1, Crk-L1, was significantly reduced by givinostat treatment in NAML1...
August 9, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28837890/fragment-analysis-represents-a-suitable-approach-for-the-detection-of-hotspot-c-7541_7542delct-notch1-mutation-in-chronic-lymphocytic-leukemia
#18
Eva Vavrova, Barbara Kantorova, Barbara Vonkova, Jitka Kabathova, Hana Skuhrova-Francova, Eva Diviskova, Ondrej Letocha, Jana Kotaskova, Yvona Brychtova, Michael Doubek, Jiri Mayer, Sarka Pospisilova
The hotspot c.7541_7542delCT NOTCH1 mutation has been proven to have a negative clinical impact in chronic lymphocytic leukemia (CLL). However, an optimal method for its detection has not yet been specified. The aim of our study was to examine the presence of the NOTCH1 mutation in CLL using three commonly used molecular methods. Sanger sequencing, fragment analysis and allele-specific PCR were compared in the detection of the c.7541_7542delCT NOTCH1 mutation in 201 CLL patients. In 7 patients with inconclusive mutational analysis results, the presence of the NOTCH1 mutation was also confirmed using ultra-deep next generation sequencing...
August 7, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28772207/bone-marrow-mesenchymal-stromal-cell-msc-gene-profiling-in-chronic-myeloid-leukemia-cml-patients-at-diagnosis-and-in-deep-molecular-response-induced-by-tyrosine-kinase-inhibitors-tkis
#19
Djamel Aggoune, Nathalie Sorel, Marie-Laure Bonnet, Jean-Michel Goujon, Karin Tarte, Olivier Hérault, Jorge Domenech, Delphine Réa, Laurence Legros, Hyacinthe Johnson-Ansa, Philippe Rousselot, Emilie Cayssials, Agnès Guerci-Bresler, Annelise Bennaceur-Griscelli, Jean-Claude Chomel, Ali G Turhan
Although it has been well-demonstrated that bone marrow mesenchymal stromal cells (MSCs) from CML patients do not belong to the Ph1-positive clone, there is growing evidence that they could play a role in the leukemogenesis process or the protection of leukemic stem cells from the effects of tyrosine kinase inhibitors (TKIs). The aim of the present study was to identify genes differentially expressed in MSCs isolated from CML patients at diagnosis (CML-MSCs) as compared to MSCs from healthy controls. Using a custom gene-profiling assay, we identified six genes over-expressed in CML-MSCs (BMP1, FOXO3, MET, MITF, NANOG, PDPN), with the two highest levels being documented for PDPN (PODOPLANIN) and NANOG...
July 26, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28759800/mesenchymal-stem-cells-derived-from-multiple-myeloma-patients-protect-against-chemotherapy-through-autophagy-dependent-activation-of-nf-%C3%AE%C2%BAb-signaling
#20
HongLiang Yang, YingChun Zheng, YiZhuo Zhang, Zeng Cao, Yingzhe Jiang
Chemotherapy resistance has been considered as a major problem for multiple myeloma (MM) treatment and bone marrow microenvironment plays a crucial role in the MM progression and chemoresistance. Recent studies reported that bone marrow mesenchymal stem cells derived from MM patients (MM-MSCs) revealed various characteristics compared with these from healthy subjects (NM-MSCs). However, the functions and mechanisms by which MM-MSCs mediate the chemotherapy resistance of MM remain unclear. In this study, we show that MM-MSCs decreased melphalan or doxorubicin-induced cell cycle arrest and apoptosis in two MM cell lines (U266 and RPMI-8226)...
July 25, 2017: Leukemia Research
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