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Leukemia Research

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https://www.readbyqxmd.com/read/28196338/telomerase-and-telomere-biology-in-hematological-diseases-a-new-therapeutic-target
#1
REVIEW
Alessandro Allegra, Vanessa Innao, Giuseppa Penna, Demetrio Gerace, Andrea G Allegra, Caterina Musolino
Telomeres are structures confined at the ends of eukaryotic chromosomes. With each cell division, telomeric repeats are lost because DNA polymerases are incapable to fully duplicate the very ends of linear chromosomes. Loss of repeats causes cell senescence, and apoptosis. Telomerase neutralizes loss of telomeric sequences by adding telomere repeats at the 3' telomeric overhang. Telomere biology is frequently associated with human cancer and dysfunctional telomeres have been proved to participate to genetic instability...
February 7, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28212899/outcome-disparities-by-insurance-type-for-patients-with-acute-myeloblastic-leukemia
#2
Dianne Pulte, Felipe A Castro, Hermann Brenner, Lina Jansen
Survival for patients with acute myeloblastic leukemia (AML) has increased during the past two decades. However, socioeconomic disparities may affect survival for some patient populations. We examine survival by insurance type for patients with AML. Using data from the Surveillance, Epidemiology, and End Results database we estimated survival according to insurance status (no insurance, Medicaid, and other insurance) for patients diagnosed with AML in the United States in 2007-2013. One, 3-, and 5-year survival was lower for patients with no insurance and Medicaid than for patients with other insurance...
February 3, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28193567/genomic-analysis-of-adult-b-all-identifies-potential-markers-of-shorter-survival
#3
Shiven Patel, Clinton C Mason, Martha J Glenn, Christian N Paxton, Sara T South, Melissa H Cessna, Julie Asch, Erin F Cobain, Dale L Bixby, Lauren B Smith, Shalini Reshmi, Julie M Gastier-Foster, Joshua D Schiffman, Rodney R Miles
B lymphoblastic leukemia (B-ALL) in adults has a higher risk of relapse and lower long-term survival than pediatric B-ALL, but data regarding genetic prognostic biomarkers are much more limited for adult patients. We identified 70 adult B-ALL patients from three institutions and performed genome-wide analysis via single nucleotide polymorphism (SNP) arrays on DNA isolated from their initial diagnostic sample and, when available, relapse bone marrow specimens to identify recurring copy number alterations (CNA)...
February 3, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28193568/markers-of-iron-deficiency-in-patients-with-polycythemia-vera-receiving-ruxolitinib-or-best-available-therapy
#4
Srdan Verstovsek, Claire N Harrison, Jean-Jacques Kiladjian, Carole Miller, Ahmad B Naim, Dilan C Paranagama, Dany Habr, Alessandro M Vannucchi
Polycythemia vera (PV) is characterized by erythropoiesis and JAK2-activating mutations, with increased risks of morbidity and mortality. Most patients with PV are iron deficient, and treatment often includes hematocrit control with phlebotomy, which may exacerbate iron deficiency-associated complications. The phase 3 RESPONSE trial evaluated the JAK1/JAK2 inhibitor ruxolitinib (n=110) versus best available therapy (BAT; n=112) in patients with PV who were hydroxyurea-resistant/intolerant. Ruxolitinib was superior to BAT for hematocrit control, reduction in splenomegaly, and blood count normalization...
January 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28171800/epigenetic-drug-combination-overcomes-osteoblast-induced-chemoprotection-in-pediatric-acute-lymphoid-leukemia
#5
Anthony Quagliano, Anilkumar Gopalakrishnapillai, Sonali P Barwe
Although there has been much progress in the treatment of acute lymphoblastic leukemia (ALL), decreased sensitivity to chemotherapy remains a significant issue. Recent studies have shown how interactions with the bone marrow microenvironment can protect ALL cells from chemotherapy and allow for the persistence of the disease. Epigenetic drugs have been used for the treatment of ALL, but there are no reports on whether these drugs can overcome bone marrow-induced chemoprotection. Our study investigates the ability of the DNA methyltransferase inhibitor azacitidine and the histone deacetylase inhibitor panobinostat to overcome chemoprotective effects mediated by osteoblasts...
January 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28171799/synergistic-antitumor-effect-of-histone-deacetylase-inhibitor-and-doxorubicin-in-peripheral-t-cell-lymphoma
#6
Huilai Zhang, Ling Dong, Qingqing Chen, Lingzhe Kong, Bin Meng, Huaqing Wang, Kai Fu, Xi Wang, Qiang Pan-Hammarström, Ping Wang, Xianhuo Wang
Chidamide (CS055) is a new and highly selective histone deacetylase inhibitor displaying significant single-agent activity in peripheral T-cell lymphoma (PTCL). But there is little known the synergistic effect between CS055 and chemotherapy. The purpose of this study is to explore the synergistic effect and molecular mechanisms of CS055 combination with Doxorubicin in PTCL cells. We found that CS055 showed dose- and time-dependent inhibition effects on PTCL cell. Meanwhile, the synergistic effect was significantly observed after combination treatment with lower drug-concentration of CS055 and Doxorubicin...
January 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28189799/combination-of-cytogenetic-classification-and-mrd-status-correlates-with-outcome-of-autologous-versus-allogeneic-stem-cell-transplantation-in-adults-with-primary-acute-myeloid-leukemia-in-first-remission
#7
Jianfeng Yao, Guixin Zhang, Chen Liang, Gang Li, Xin Chen, Qiaoling Ma, Weihua Zhai, Donglin Yang, Yi He, Erlie Jiang, Sizhou Feng, Mingzhe Han
Both autologous and allogeneic stem cell transplantation (auto- and allo-SCT) are treatment choice for adults with acute myeloid leukemia (AML) after complete remission (CR). However, the decision-making remains controversial in some situations. To figure out the treatment choice, we retrospectively investigated 172 consecutive patients with primary AML who received auto- (n=46) or allo-SCT (n=126) from a single transplant center. Auto- and allo-SCT group demonstrated comparable overall survival (OS) and disease-free survival (DFS) (P=0...
January 24, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28152414/coexisting-and-cooperating-mutations-in-npm1-mutated-acute-myeloid-leukemia
#8
Jay L Patel, Jonathan A Schumacher, Kimberly Frizzell, Shelly Sorrells, Wei Shen, Adam Clayton, Rakhi Jattani, Todd W Kelley
NPM1 insertion mutations represent a common recurrent genetic abnormality in acute myeloid leukemia (AML) patients. The frequency of these mutations varies from approximately 30% overall up to 50% in patients with a normal karyotype. Several recent studies have exploited advances in massively parallel sequencing technology to shed light on the complex genomic landscape of AML. We hypothesize that variant allele fraction (VAF) data derived from massively parallel sequencing studies may provide further insights into the clonal architecture and pathogenesis of NPM1-driven leukemogenesis...
January 23, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28157629/the-epigenetically-regulated-mir-34a-targeting-c-src-suppresses-raf-mek-erk-signaling-pathway-in-k-562-cells
#9
Yang Yang, Li Ding, Zi-Kuan Guo, Xiao-Li Zheng, Li-Sheng Wang, Hui-Yan Sun, Zhan-Guo Jin, Heng-Xiang Wang
Previous reports show that miR-34a suppressed K-562 cell proliferation and contributed to megakaryocytic differentiation of K-562 cells. Here, we reported that miR-34a, a tumor suppressor gene, is down-regulated in the K-562 cells and chronic myeloid leukemia (CML) patients due to aberrant DNA hypermethylation. c-SRC is a target of miR-34a. Restoring miR-34a expression resulted in down-regulation of c-SRC and phosphorylated (Tyr416) c-SRC protein in K-562 cells, which consequently triggered suppression of the RAF/MEK/ERK signaling pathway to decrease cell proliferation...
January 22, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28131982/use-of-5-azacitidine-for-therapy-related-myeloid-neoplasms-in-patients-with-concomitant-active-neoplastic-disease
#10
M Annereau, C Willekens, L El Halabi, C Chahine, V Saada, N Auger, A Danu, E Bermudez, J Lazarovici, D Ghez, A Leary, B Pistilli, F Lemare, E Solary, S de Botton, R-P Desmaris, J-B Micol
BACKGROUND: Patients diagnosed with therapy-related myeloid neoplasms (TRMN) with concomitant active neoplastic disorder (CAND) are usually proposed for best supportive care (BSC). We evaluated the feasibility of using 5-azacytidine (AZA) in this setting. METHODS: All patients referred to Gustave Roussy between 2010 and 2015 for TRMN diagnosis (less than 30% blast) and eligible for AZA treatment were included. Patients with CAND proposed for BSC were also described...
January 20, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28161606/the-absolute-number-of-regulatory-t-cells-in-unmanipulated-peripheral-blood-grafts-predicts-the-occurrence-of-acute-graft-versus-host-disease-post-haplo-identical-hematopoietic-stem-cell-transplantation
#11
Li Ding, Heng Zhu, Yang Yang, Hong-Min Yan, Hai-Hong Zhang, Dong-Mei Han, Zhi-Dong Wang, Xiao-Li Zheng, Jing Liu, Ling Zhu, Mei-Xue, Zi-Kuan Guo, Heng-Xiang Wang
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) have been reported to play a central role in suppressing acute graft-versus-host disease (aGVHD), but whether the Treg contents of grafts correlates with the occurrence of aGVHD post haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) remains unclear. In the present study, changes in Tregs in peripheral blood (PB) were followed before and after granulocyte colony-stimulating factor (G-CSF) mobilization. In addition, functional analyses of Tregs in PB grafts and bone marrow (BM) grafts were performed...
January 18, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28122282/unexpected-cross-reactivity-of-anti-cathepsin-b-antibodies-leads-to-uncertainties-regarding-the-mechanism-of-action-of-anti-cd20-monoclonal-antibody-ga101
#12
Wei Wen Chien, Charlène Niogret, Romain Jugé, Loïc Lionnard, Aurélie Cornut-Thibaut, Jérôme Kucharczak, Ariel Savina, Gilles Salles, Abdel Aouacheria
GA101, also known as obinutuzumab or Gazyva (Gazyvaro), is a glycoengineered type II humanized antibody that targets the CD20 antigen expressed at the surface of B-cells. This novel anti-CD20 antibody is currently assessed in clinical trials with promising results as a single agent or as part of therapeutic combinations for the treatment of B-cell malignancies. Detailed understanding of the mechanisms of GA101-induced cell death is needed to get insight into possible resistance mechanisms occurring in patients...
January 18, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28167452/tet2-exon-2-skipping-is-an-independent-favorable-prognostic-factor-for-cytogenetically-normal-acute-myelogenous-leukemia-aml-tet2-exon-2-skipping-in-aml
#13
Aminetou Mint Mohamed, Marie Balsat, Catherine Koering, Delphine Maucort-Boulch, Nicolas Boissel, Lea Payen-Gay, Meyling Cheok, Hussein Mortada, Didier Auboeuf, Christiane Pinatel, Mohamed El-Hamri, Isabelle Tigaud, Sandrine Hayette, Charles Dumontet, Emeline Cros, Pascale Flandrin-Gresta, Olivier Nibourel, Claude Preudhomme, Xavier Thomas, Franck-Emmanuel Nicolini, Françoise Solly, Denis Guyotat, Lydia Campos, Mauricette Michallet, Antony Ceraulo, Franck Mortreux, Eric Wattel
In AML, approximately one-third of expressed genes are abnormally spliced, including aberrant TET2 exon 2 expression. In a discovery cohort (n=99), TET2 exon 2 skipping (TET2E2S) was found positively associated with a significant reduction in the cumulative incidence of relapse (CIR). Age, cytogenetics, and TET2E2S were independent prognostic factors for disease-free survival (DFS), and favorable effects on outcomes predominated in cytogenetic normal (CN)-AML and younger patients. Using the same cutoff in a validation cohort of 86 CN-AML patients, TET2E2S(high) patients were found to be younger than TET2(low) patients without a difference in the rate of complete remission...
January 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28122281/anti-cancer-effect-of-clofazimine-as-a-single-agent-and-in-combination-with-cisplatin-on-u266-multiple-myeloma-cell-line
#14
İpek Z Durusu, Hazal H Hüsnügil, Heval Ataş, Ayşenur Biber, Selin Gerekçi, Ezgi A Güleç, Can Özen
Multiple Myeloma (MM) is a malignant neoplasm of bone marrow plasma B cells with high morbidity. Clofazimine (CLF) is an FDA-approved leprostatic, anti-tuberculosis, and anti-inflammatory drug that was previously shown to have growth suppression effect on various cancer types such as hepatocellular, lung, cervix, esophageal, colon, and breast cancer as well as melanoma, neuroblastoma, and leukemia. The objective of this study was to evaluate the anticancer effect and mechanism of CLF on U266 MM cell line. CLF (10μM, 24h) treatment resulted up to 72% growth suppression on a panel of hematological cell lines...
January 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28119224/clinical-significance-of-isolated-del-7p-in-myeloid-neoplasms
#15
Hatice Deniz Gur, Sa A Wang, Zhenya Tang, Shimin Hu, Shaoying Li, L Jeffrey Medeiros, Guilin Tang
Sole del(7p) is a rare finding in myeloid neoplasms and its clinical significance is largely unknown. Here we report 10 patients with isolated del(7p), 4 had acute myeloid leukemia (AML), 2 myelodysplastic syndromes (MDS), 1 chronic myelomonocytic leukemia (CMML), 1 primary myelofibrosis (PMF), and 2 AML in remission. Seven patients had large and 3 had small del(7p) clone. For patients with AML, 3 acquired del(7p) either at disease relapse or disease progression, then became refractory to therapy and died shortly thereafter (median 5 months)...
January 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28157628/characterization-of-treatment-and-outcomes-in-a-population-based-cohort-of-patients-with-chronic-lymphocytic-leukemia-referred-for-cytogenetic-testing-in-british-columbia-canada
#16
Steven J Huang, Lauren J Lee, Alina S Gerrie, Tanya L Gillan, Helene Bruyere, Monica Hrynchak, Adam C Smith, Aly Karsan, Khaled M Ramadan, Kavisha S Jayasundara, Cynthia L Toze
This study evaluates outcomes in chronic lymphocytic leukemia (CLL) based on first-line therapy in a large consecutive population-based cohort of 669 patients with fluorescence in-situ hybridization (FISH) data in British Columbia, Canada during the period when chemoimmunotherapy was standard first-line treatment. When analyzed as a time-dependent variable, patients who required treatment (n=336) had a 4.7 times higher hazard of death than patients who did not (95% confidence interval 2.8-7.9, P<0.001). The majority of patients received fludarabine-rituximab (FR) in front-line...
January 15, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28152413/over-expression-of-cd200-predicts-poor-prognosis-in-mds
#17
Jia-Xi Chen, Li-Ping Mei, Bao-Guo Chen, Dong-Lian Wang, Wen-da Luo, Li-Fei Luo, Ruyue Lu, Rui Zheng, Li Zhang
BACKGROUND: We studied the expression of CD200 in a series of 101 patients with diagnosis of myelodysplastic syndrome (MDS), to evaluate its impact on outcome and its possible association with other known prognostic factors. MATERIAL/METHODS: The CD200 was detected by flow cytometry, and the chromosome karyotypes were determined by G banding respectively. The Mann-Whitney U test was used to analyze the association among CD200 expression and clinical features. In addition, the overall survival and AML transformation of the MDS patients according to the expression level of CD200 was also explored...
January 15, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28110206/an-epstein-barr-virus-susceptible-immature-t-cell-line-will4-established-from-a-patient-with-t-lymphoblastic-lymphoma-bearing-cd21-and-a-clonal-ebv-genome
#18
Hiroki Hosoi, Ken-Ichi Imadome, Shinobu Tamura, Kodai Kuriyama, Shogo Murata, Yusuke Yamashita, Toshiki Mushino, Takehiro Oiwa, Hiroshi Kobata, Akinori Nishikawa, Hideki Nakakuma, Nobuyoshi Hanaoka, Yasushi Isobe, Kouichi Ohshima, Takashi Sonoki
We managed a patient with an Epstein-Barr virus-associated T-cell lymphoblastic lymphoma. Mediastinal tumor cells at initial admission were positive for CD4, CD8, and TdT. Interestingly, a lymph node at necropsy was compatible for a CD4-positive peripheral T-cell lymphoma without CD8 and TdT expression, suggesting a different phenotype from the mediastinal tumor. Tumor cells in pleural effusion continued to proliferate in in vitro and were designated as WILL4. WILL4 cells were positive for CD3, CD4, CD8, CD21, T-cell receptor (TcR) αβ, and TdT, indicating a similar phenotype to thymocytes...
January 15, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28119225/the-eif2-alpha-kinase-hri-is-a-novel-therapeutic-target-in-multiple-myeloma
#19
Nicholas Burwick, Michael Y Zhang, Pilar de la Puente, Abdel Kareem Azab, Teresa S Hyun, Melisa Ruiz-Gutierrez, Marilyn Sanchez-Bonilla, Tomoka Nakamura, Jeffrey J Delrow, Vivian L MacKay, Akiko Shimamura
Dexamethasone (dex) induces apoptosis in multiple myeloma (MM) cells and is a frontline treatment for this disease. However resistance to dex remains a major challenge and novel treatment approaches are needed. We hypothesized that dex utilizes translational pathways to promote apoptosis in MM and that specific targeting of these pathways could overcome dex-resistance. Global unbiased profiling of mRNA translational profiles in MM cells treated with or without dex revealed that dex significantly repressed eIF2 signaling, an important pathway for regulating ternary complex formation and protein synthesis...
January 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28135648/current-approach-to-the-treatment-of-chronic-myeloid-leukaemia
#20
REVIEW
Ivan Pasic, Jeffrey H Lipton
Of all the cancers, chronic myeloid leukaemia (CML) has witnessed the most rapid evolution of the therapeutic milieu in recent decades. The introduction of tyrosine kinase inhibitors (TKIs) as a therapeutic option has profoundly changed patient experience and outcome. The availability of multiple new highly effective therapies has increasingly underscored the importance of a good understanding of the underlying pathophysiological basis in CML, as well as patient-specific factors in choosing the right treatment for every individual...
January 11, 2017: Leukemia Research
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