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Leukemia Research

Flavia da Cunha Vasconcelos, Marcos Antonio Mauricio Scheiner, Arthur Moellman-Coelho, André Luiz Mencalha, Ilana Zalcberg Renault, Vivian Mary Rumjanek, Raquel Ciuvalschi Maia
Despite the favorable clinical evolution of patients with chronic myeloid leukemia (CML), resistance or intolerance to imatinib is present in approximately 35% of patients. Sokal score is a widely used risk factor, however efflux and influx transporters are provisional risk factors implicated in imatinib resistance. This study analyzed Sokal score, ABCB1, ABCG2 and OCT1 mRNA transporter expression levels as well as P-glycoprotein expression and efflux transporters activity to seek a possible correlation between these factors and the molecular response at 12 months from imatinib start as well as 8-year overall survival (OS)...
October 12, 2016: Leukemia Research
Michael D Diamantidis, Daphne Papanastasiou
No abstract text is available yet for this article.
October 12, 2016: Leukemia Research
Himalee S Sabnis, Heath L Bradley, Shweta Tripathi, Wen-Mei Yu, William Tse, Cheng-Kui Qu, Kevin D Bunting
Current therapy for acute myeloid leukemia (AML) primarily includes high-dose cytotoxic chemotherapy with or without allogeneic stem cell transplantation. Targeting unique cellular metabolism of cancer cells is a potentially less toxic approach. Monotherapy with mitochondrial inhibitors like metformin have met with limited success since escape mechanisms such as increased glycolytic ATP production, especially in hyperglycemia, can overcome the metabolic blockade. As an alternative strategy for metformin therapy, we hypothesized that the combination of 6-benzylthioinosine (6-BT), a broad-spectrum metabolic inhibitor, and metformin could block this drug resistance mechanism...
October 5, 2016: Leukemia Research
Jing Chen, Jie Cheng, Juan Yi, Bei Xie, Li Lin, Zhuan Liu, Huaishun Zhao, Bei Wang, Ziying Ai, Yue Yang, Hulai Wei
There is no cross-resistance between arsenic trioxide and conventional chemotherapeutics. Classical multi-drug resistant (MDR) cells remain sensitive to arsenic trioxide, which may even reverse the drug resistance. Arsenic trioxide is also effective in leukemias/tumors that persist despite conventional cytotoxic or targeted drugs. We obtained a highly arsenic-resistant MDR leukemic cell line, HL-60/RS, by exposing leukemic HL-60 cells to adriamycin selection. We compared the arsenic sensitivity, and the expression and responses to arsenic of the arsenic-related transporters, MRP1, MRP2, and ASNA1, in paired parent/arsenic-resistant HL-60/RS/HL-60 and arsenic-sensitive/parental K562/ADM/K562 cells...
October 3, 2016: Leukemia Research
Rama Nanah, Darci Zblewski, Mrinal S Patnaik, Kebede Begna, Rhett Ketterling, Vivek N Iyer, William J Hogan, Mark R Litzow, Aref Al-Kali
A variety of interstitial Lung Diseases (ILD) have been described in patients with myelodysplastic syndromes (MDS) with possible etiologies including autoimmunity, drug related toxicity, and recurrent infections. A comprehensive study of ILD in MDS patients has not been previously performed. Out of 827 consecutive biopsy proven MDS patients seen at our institution from June 1970-May 2010, 18 (2%) were found to have ILD. There was no statistical significance in baseline characteristics between patients with ILD (ILD +) vs those without ILD (ILD-)...
October 3, 2016: Leukemia Research
Ronan T Swords, Peter L Greenberg, Andrew H Wei, Simon Durrant, Anjali S Advani, Mark S Hertzberg, Ian D Lewis, Gabriel Rivera, Dita Gratzinger, Alice C Fan, Dean W Felsher, Jorge E Cortes, Justin M Watts, Geoff T Yarranton, Jackie M Walling, Jeffrey E Lancet
EphA3 is an Ephrin receptor tyrosine kinase that is overexpressed in most hematologic malignancies. We performed a first-in-human multicenter phase I study of the anti-EphA3 monoclonal antibody KB004 in refractory hematologic malignancies in order to determine safety and tolerability, along with the secondary objectives of pharmacokinetics (PK) and pharmacodynamics (PD) assessments, as well as preliminary assessment of efficacy. Patients were enrolled on a dose escalation phase (DEP) initially, followed by a cohort expansion phase (CEP)...
September 28, 2016: Leukemia Research
Stina Söderlund, Lisa Christiansson, Inger Persson, Henrik Hjorth-Hansen, Johan Richter, Bengt Simonsson, Satu Mustjoki, Ulla Olsson-Strömberg, Angelica Loskog
BACKGROUND AND AIMS: The simultaneous measurement of many proteins is now possible using multiplex assays. In this pilot study we investigated a total of 124 proteins in plasma from chronic myeloid leukemia (CML) patients with the purpose of identifying proteins that are differently expressed at diagnosis and after tyrosine kinase inhibitor (TKI) treatment initiation. METHODS: Samples were taken from 14 CML patients at diagnosis and after three months of TKI treatment (imatinib or dasatinib)...
September 27, 2016: Leukemia Research
Ryo Shimizu, Tomoya Muto, Kazumasa Aoyama, Kwangmin Choi, Masahiro Takeuchi, Shuhei Koide, Nagisa Hasegawa, Yusuke Isshiki, Emi Togasaki, Chika Kawajiri-Manako, Yuhei Nagao, Shokichi Tsukamoto, Shio Sakai, Yusuke Takeda, Naoya Mimura, Chikako Ohwada, Emiko Sakaida, Tohru Iseki, Daniel T Starczynowski, Atsushi Iwama, Koutaro Yokote, Chiaki Nakaseko
Expression of the tumor suppressor gene NR4A3 is silenced in the blasts of acute myeloid leukemia (AML), irrespective of the karyotype. Although the transcriptional reactivation of NR4A3 is considered to have a broad-spectrum anti-leukemic effect, the therapeutic modalities targeting this gene have been hindered by our minimal understanding of the transcriptional mechanisms regulating its expression, particularly in human AML. Here we show the role of intragenic DNA hypermethylation in reducing the expression of NR4A3 in AML...
September 26, 2016: Leukemia Research
Chen Wang, Xu-Fei Huang, Qian-Qian Cai, Xin-Xin Cao, Hao Cai, Daobin Zhou, Jian Li
Vascular endothelial growth factor (VEGF) is pathognomonically elevated in patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome. However, its source of overproduction is unclear. As clinical improvement is almost always associated with VEGF reduction after anti-plasma cell therapy, its increase at diagnosis has been attributed to the underlying monoclonal gammopathy, although direct evidence is still lacking. In the current study, we systemically measured VEGF levels in POEMS patients, before and after treatment...
September 26, 2016: Leukemia Research
Sara E F Kost, Eric D J Bouchard, Élise LaBossière, Xibiao Ye, Michelle L Queau, William S Liang, Versha Banerji, Spencer B Gibson, Sachin Katyal, James B Johnston
Bendamustine (BEN) has structural similarities to an alkylating agent and a nucleoside analog, and effective against tumor cells that are resistant to standard therapy. In this study we compared the activities of BEN against that of the alkylating agent, chlorambucil (CLB), and the nucleoside analogs, fludarabine (FLU) and deoxyadenosine/pentostatin (dADO/PEN), in primary chronic lymphocytic leukemia (CLL) cells in vitro. Cross-resistance was observed between BEN, CLB and FLU, with previously treated patients or those with a deletion 17p being most resistant...
September 20, 2016: Leukemia Research
Aya Nakaya, Shinya Fujita, Atsushi Satake, Takahisa Nakanishi, Yoshiko Azuma, Yukie Tsubokura, Masaaki Hotta, Hideaki Yoshimura, Kazuyoshi Ishii, Tomoki Ito, Shosaku Nomura
Reactivation of hepatitis B virus (HBV) infection is a well-recognized and potentially fatal complication in patients treated with chemotherapy for lymphoid malignancies. Although several guidelines recommend antiviral prophylaxis and/or monitoring for HBV-DNA, there is no consensus over what time period these should occur. Clinically, we have encountered delayed reactivation of HBV infections and have reported 12 cases of reactivation in patients. Among them, five patients developed HBV reactivation more than a year after they completed their chemotherapy...
September 17, 2016: Leukemia Research
Ming Hong, Yi Xia, Yu Zhu, Hui-Hui Zhao, Han Zhu, Yue Xie, Lei Fan, Li Wang, Kou-Rong Miao, Hui Yu, Yu-Qing Miao, Wei Wu, Hua-Yuan Zhu, Yao-Yu Chen, Wei Xu, Si-Xuan Qian, Jian-Yong Li
OBJECTIVES: Circulating chronic lymphocytic leukemia (CLL) cells appear not to be overly utilizing aerobic glycolysis. However, recurrent contact with CLL cells in a stromal microenvironment leads to increased aerobic glycolysis and the cells' overall glycolytic capacity, which promotes cell survival and proliferation. TP53-induced glycolysis and apoptosis regulator (TIGAR) has been directly implicated in cellular metabolism in the control of glycolysis. TIGAR inhibits glycolysis and protects cells from intracellular reactive oxygen species (ROS)-associated apoptosis...
September 15, 2016: Leukemia Research
Na Hee Lee, Young Bae Choi, Eun-Sang Yi, Soo Hyun Lee, Hee-Jin Kim, Ji Won Lee, Ki Woong Sung, Hong Hoe Koo, Keon Hee Yoo
Monosomal karyotype (MK) is known as a far end of the unfavorable cytogenetics in adult acute myeloid leukemia (AML), while available data in childhood AML is scarce. In this study, we investigated the prevalence and prognostic value of MK with retrospectively analyzed 119 patients newly diagnosed with childhood de novo AML. Ten patients (8.4%) revealed to have MK. All MK-positive (MK(+)) AML were associated with complex cytogenetic abnormalities and belonged to the cytogenetic adverse-risk group. Nine of MK(+) patients (90%) achieved complete remission...
September 15, 2016: Leukemia Research
Stefano Molica, Aaron Polliack
In the past decade the introduction of targeted therapies has dramatically transformed the landscape of treatment for chronic lymphocytic leukemia (CLL). Whether this new therapeutic scenario will modify the current prevalence statistics and natural history of autoimmune cytopenias complicating CLL is still a matter of debate. Here we present a comprehensive review of the literature on this topic, with special emphasis on the incidence of autoimmune hemolytic anemia (AIHA). The potential to induce autoimmune cytopenia has been studied mostly with ibrutinib, a first- in-class bruton kinase (BTK) inhibitor, licensed for the treatment of relapsed/refractory high-risk CLL...
September 14, 2016: Leukemia Research
Yu Ouyang, Fei Zhong, Qiru Wang, Linlin Ding, Peipei Zhang, Lingling Chen, Yuchan Wang, Chun Cheng
DIX domain containing 1 (DIXDC1), is a human homolog of Ccd1, a DIX domain containing protein in zebrafish. The present study was undertaken to determine the expression and biologic function of DIXDC1 in Non-Hodgkin's lymphoma (NHL). Clinically, we detected that the expression of DIXDC1 was significantly lower in the indolent lymphomas compared with the progressive lymphomas by immunohistochemistry analysis. Functionally, we found that DIXDC1 could promote cell proliferation via modulating cell cycle progression and PI3K/AKT signaling pathway in NHLs...
September 8, 2016: Leukemia Research
Marie-Christine Kyrtsonis, Dimitrios Maltezas
No abstract text is available yet for this article.
September 6, 2016: Leukemia Research
Chan Kyu Kim, Dong Hoon Han, Young Seok Ji, Min Sung Lee, Chang Wook Min, Seong Kyu Park, Se Hyung Kim, Jina Yun, Hyun Jeung Kim, Kyoung Ha Kim, Kyu Taek Lee, Jong Ho Won, Dae Sik Hong, Hee Kyung Kim
Angiogenesis occurs in response to tissue ischemia and wound healing, and contributes to the pathogenesis of a variety of diseases, such as benign and malignant neoplasia. Several studies have measured bone marrow microvessel density (MVD) in MDS patients and acute myeloid leukemia (AML) patients transformed from MDS, and MVD was higher in MDS patients than controls, but was lower than in AML patients. Vascular endothelial growth factor (VEGF) is expressed in bone marrow blast cells, and an autocrine VEGF signaling mechanism has been established in MDS...
September 5, 2016: Leukemia Research
Yinjun Lou, Shanshan Suo, Hongyan Tong, Wenbin Qian, Wenyuan Mai, Haitao Meng, Wenjuan Yu, Juyin Wei, Jie Jin
Acute promyelocytic leukemia (APL) is a medical emergency. In order to evaluate the usefulness of initial coagulation parameters in the predictive value of APL diagnosis, 1304 consecutive newly diagnosed acute leukemia patients, including APL (n=211), non-APL acute myeloid leukemia (n=781) and acute lymphoblastic leukemia (n=312) were retrospectively evaluated between January 2011 and May 2015. The area under curve (AUC) of fibrinogen was the largest among the coagulation markers based on receiver operating characteristic (ROC) analysis...
September 5, 2016: Leukemia Research
Gilles M Leclerc, Shuhua Zheng, Guy J Leclerc, Joanna DeSalvo, Ronan T Swords, Julio C Barredo
Acute lymphoblastic leukemia (ALL) is the leading cause of cancer-related death in children, and cure rates for adults remain dismal. Further, effective treatment strategies for relapsed/refractory ALL remain elusive. We previously uncovered that ALL cells are prone to apoptosis via endoplasmic reticulum (ER) stress/unfolded protein response (UPR)-mediated mechanisms. We investigated the antineoplastic activity of pevonedistat(®), a novel NEDD8-activating enzyme inhibitor that targets E3 cullin-RING ligases (CRLs) dependent proteasomal protein degradation, in ALL...
September 5, 2016: Leukemia Research
G Visani, A Manti, L Valentini, B Canonico, F Loscocco, A Isidori, E Gabucci, P Gobbi, S Montanari, M Rocchi, S Papa, A M Gatti
The increase in the incidence of acute myeloid leukemia (AML) may suggest a possible environmental etiology. PM2.5 was declared by IARC a Class I carcinogen. No report has focused on particulate environmental pollution together with AML. The study investigated the presence and composition of particulate matter in blood with a Scanning Electron Microscope coupled with an Energy Dispersive Spectroscope, a sensor capable of identifying the composition of foreign bodies. 38 peripheral blood samples, 19 AML cases and 19 healthy controls, were analyzed...
September 3, 2016: Leukemia Research
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