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https://www.readbyqxmd.com/read/29143282/hypomethylating-agents-for-treatment-and-prevention-of-relapse-after-allogeneic-blood-stem-cell-transplantation
#1
REVIEW
Thomas Schroeder, Christina Rautenberg, Rainer Haas, Ulrich Germing, Guido Kobbe
Despite the curative potential of allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), many patients will relapse. Until recently therapeutic options mainly consisted of palliative care, chemotherapy, donor lymphocyte infusions and second transplantation in selected cases. Still many patients either do not tolerate intensive therapies or do not achieve durable remissions and will finally succumb. Given this unmet medical need the hypomethylating agents (HMA), Azacitidine (Aza) and Decitabine (DAC) have been tested as salvage therapy in patients with myeloid malignancies relapsing after allo-SCT...
November 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29139328/repression-of-oxidative-phosphorylation-sensitizes-leukemia-cell-lines-to-cytarabine
#2
Burcu Yucel, Mehmet Sonmez
OBJECTIVES: Leukemia is a group of bone marrow cancers and drug resistance is one of the challenges in treatment. Caffeic acid phenethyl ester's (CAPE's) anti-proliferative and apoptotic properties have been reported in leukemia cell lines. However, CAPE's effect on drug resistance and cellular metabolism is still unknown. Thus, in this study, we aimed to explore CAPE's effect on drug resistance and oxidative phosphorylation (oxphos). METHODS: Leukemia cell lines NB-4, HL-60, and K562 were treated with CAPE...
November 15, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29138222/decitabine-enhances-targeting-of-aml-cells-by-cd34-progenitor-derived-nk-cells-in-nod-scid-il2rg-null-mice
#3
Jeannette Cany, Mieke W H Roeven, Janneke S Hoogstad-van Evert, Willemijn Hobo, Frans Maas, Rosalia Franco Fernandez, Nicole M A Blijlevens, Walter J van der Velden, Gerwin Huls, Joop H Jansen, Nicolaas P M Schaap, Harry Dolstra
Combining NK cell adoptive transfer with hypomethylating agents (HMA) is an attractive therapeutic approach for patients with acute myeloid leukemia (AML). However, data regarding the impact of HMA on NK cell functionality are mostly derived from in vitro studies with high non-clinical relevant drug concentrations. Here, we report a comparative study of azacitidine and decitabine in combination with allogeneic NK cells generated from CD34(+) hematopoietic stem and progenitor cells (HSPC-NK cells) in in vitro and in vivo AML models...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29137406/the-forkhead-box-c1-foxc1-transcription-factor-is-downregulated-in-acute-promyelocytic-leukemia
#4
Emiliano Fabiani, Giulia Falconi, Nélida Inés Noguera, Ernestina Saulle, Laura Cicconi, Mariadomenica Divona, Cristina Banella, Alessandra Picardi, Anna Maria Cerio, Letizia Boe, Massimo Sanchez, Elvira Pelosi, Ugo Testa, Francesco Lo-Coco, Maria Teresa Voso
Forkhead box (FOX) genes encode transcription factors, which regulate embryogenesis and play an important role in hematopoietic differentiation and in mesenchymal niche maintenance. Overexpression of the family member FOXC1 has been reported in solid tumors and acute myeloid leukemia (AML). We studied FOXC1 expression and function in acute promyelocytic leukemia (APL) and normal hematopoietic progenitors. FOXC1 mRNA and protein levels were significantly lower in primary marrow samples from 27 APL patients, as compared to samples obtained from 27 patients with other AML subtypes, and 5 normal CD34+ hematopoietic cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29129488/dna-hypomethylating-agents-as-epigenetic-therapy-before-and-after-allogeneic-hematopoietic-stem-cell-transplantation-in-myelodysplastic-syndromes-and-juvenile-myelomonocytic-leukemia
#5
REVIEW
Christian Flotho, Sebastian Sommer, Michael Lübbert
Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine...
November 9, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29124072/decitabine-induced-changes-in-human-myelodysplastic-syndrome-cell-line-skm-1-are-mediated-by-foxo3a-activation
#6
Wen Zeng, Hanjun Dai, Ming Yan, Xiaojun Cai, Hong Luo, Min Ke, Zeming Liu
The epigenetic silencing of tumor suppressor genes in myelodysplastic syndromes (MDS) can potentially confer a growth advantage to individual cellular clones. Currently, the recommended treatment for patients with high-risk MDS is the methylation agent decitabine (DAC), a drug that can induce the reexpression of silenced tumor suppressor genes. We investigated the effects of DAC treatment on the myeloid MDS cell line SKM-1 and investigated the role of FOXO3A, a potentially tumor-suppressive transcription factor, by silencing its expression prior to DAC treatment...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29100410/chidamide-and-decitabine-can-synergistically-induce-apoptosis-of-hodgkin-lymphoma-cells-by-up-regulating-the-expression-of-pu-1-and-klf4
#7
Tao Jiang, Fujue Wang, Lianjie Hu, Xiaomin Cheng, Yuhuan Zheng, Ting Liu, Yongqian Jia
Epigenetic abnormalities play important roles in the pathogenesis of Hodgkin lymphoma (HL). Highly expressed class I histone acetyltransferase (HDAC) and hyper-methylation of the promoter region of tumor suppressor genes have been demonstrated in Hodgkin lymphoma. In this paper, we investigated the synergistic effects of combination treatment of chidamide, a selective HDAC inhibitor, and decitabine, a demethylation agent, for HL cell lines and explored a new strategy for treating HL. The apoptosis rates, cell cycle, mitochondrial transmembrane potentials, epigenetic changes and gene expression of HL cell lines treated with chidamide as a single agent and in combination with decitabine were tested...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29074044/dnmt1-is-predictive-of-survival-and-associated-with-ki-67-expression-in-r-chop-treated-diffuse-large-b-cell-lymphomas
#8
Suet Kee Loo, Ewe Seng Ch'ng, Charles H Lawrie, María Arestin Muruzabal, Ayman Gaafar, María Puente Pomposo, Azlan Husin, Md Salzihan Md Salleh, Alison H Banham, Lars M Pedersen, Michael B Møller, Tina M Green, Kah Keng Wong
DNMT1 is a target of approved anti-cancer drugs including decitabine. However, the prognostic value of DNMT1 protein expression in R-CHOP-treated diffuse large B-cell lymphomas (DLBCLs) remains unexplored. Here we showed that DNMT1 was expressed in the majority of DLBCL cases (n = 209/230, 90.9%) with higher expression in germinal centre B-cell-like (GCB)-DLBCL subtype. Low and negative DNMT1 expression (20% cut-off, n = 33/230, 14.3%) was predictive of worse overall survival (OS; p < 0.001) and progression-free survival (PFS; p < 0...
October 23, 2017: Pathology
https://www.readbyqxmd.com/read/29070129/-clinical-efficacy-of-low-dose-decitabine-combined-with-cag-regimen-in-patients-with-myelodysplastic-syndrome-refractory-anemia-with-excess-blasts-mds-raeb
#9
Meng Wang, Hao-Hao Han, Rong Guo, Yan-Fang Liu, Zhong-Xing Jiang, Hui Sun
OBJECTIVE: To investigate the clinical efficacy of low-dose decitabine combined with CAG regimen in patients with myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB) through retrospective analysis. METHODS: Thirty-six patients with MDS-RAEB who ever received low-dose decitabine combined with CAG regimen were enrolled into decitabine + CAG group and 40 patients with MDS-RAEB treated by decitabine alone in our center were enolled into the control group...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29070128/-clinical-observation-of-therapeutic-regimen-consisted-of-decitabine-combined-with-low-dose-ia-regimen-for-myelodysplastic-syndrome-eb
#10
Di Wu, Jin-Xia Hao, Jing Li, Mei Zhang
OBJECTIVE: To investigate the clinical efficacy of decitabine combined with low-dose IA for treating patients with myelodysplastic syndrome-EB. METHODS: Thirty-seven cases of myelodysplastic syndrome-EB patients diagnosed in the First Affiliated Hospital of Xi'an Jiaotong University from June 2015 to January 2017 were analyzed retrospectively. These patients accepted DAC+IA(19 cases) and DAC(18 cases) treatment separately, and the differences of clinical efficacy between them were compared...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29070127/-inhibitory-effect-of-decitabine-on-proliferation-of-mds-l-cells-and-its-mechanism
#11
Dong Wu, Yao Zhang, You-Shan Zhao, Juan Guo, Chun-Kang Chang
OBJECTIVE: To investigate the inhibitory effect of decitabine (DAC) in various dosages on the proliferention of MDS-RAEB cell line MDS-L and its mechanism. METHODS: LC-MS/MS method was used to test the blood DAC concentration of 2 groups of MDS patients being treated with DAC 20 and 15 mg/m(2)×5 d. In according to the various blood DAC concentration levels, the MDS-L cells were treated with different DAC dosages for 24, 48, 72 and 96 h, respectively. The CCK-8 method was applied to determine the cell proliferation, the flow cytometry was used to analyze the cell cycle and cell apoptosis changes, the P15(INK4B) DNA methylation status was measured by methylation specific PCR using EZ DNA Methylation-Gold Kit...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29069007/successful-eltrombopag-treatment-of-severe-refractory-thrombocytopenia-in-chronic-myelomonocytic-leukemia-two-cases-reports-a-care-compliant-article
#12
Yayue Gao, Ming Gong, Chunxia Zhang, Xudong Kong, Yigai Ma
RATIONALE: Thrombocytopenia in chronic myelomonocytic leukemia (CMML) is usually attributed to impaired marrow production resulting from cytotoxic drug use or CMML itself ("CMML-induced thrombocytopenia"). In very rare cases, immune thrombocytopenia (ITP) can be a complication of CMML ("CMML-associated ITP"). However, treatment of severe thrombocytopenia in patients with CMML is still a challenge. PATIENT CONCERNS: Case 1 was a 61-year-old female patient admitted to our hospital because of skin petechiae and purpura for 6 days...
October 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29058375/patterns-of-infectious-complications-in-acute-myeloid-leukemia-and-myelodysplastic-syndromes-patients-treated-with-10-day-decitabine-regimen
#13
Alaa M Ali, Daniel Weisel, Feng Gao, Geoffrey L Uy, Amanda F Cashen, Meagan A Jacoby, Lukas D Wartman, Armin Ghobadi, Iskra Pusic, Rizwan Romee, Todd A Fehniger, Keith E Stockerl-Goldstein, Ravi Vij, Stephen T Oh, Camille N Abboud, Mark A Schroeder, Peter Westervelt, John F DiPersio, John S Welch
Decitabine has been explored as a reduced-intensity therapy for older or unfit patients with acute myeloid leukemia (AML). To better understand the risk of infections during decitabine treatment, we retrospectively examined the culture results from each infection-related serious adverse event that occurred among 85 AML and myelodysplastic syndromes (MDS) patients treated in a prospective clinical study using 10-day cycles of decitabine at Washington University School of Medicine. Culture results were available for 163 infection-related complications that occurred in 70 patients: 90 (55...
October 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29058281/decitabine-for-relapsed-acute-lymphoblastic-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#14
Jie-Ke Cui, Yin Xiao, Yong You, Wei Shi, Qing Li, Yi Luo, Lin Jiang, Zhao-Dong Zhong
Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine (DAC) for treating patients with acute lymphoblastic leukemia (ALL) who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy...
October 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/29045939/very-low-dose-decitabine-is-effective-in-treating-intermediate-or-high-risk-myelodysplastic-syndrome
#15
Hongmin Li, Liru Wang, Yue Wu, Li Su, Hong Zhao, Yongqing Zhang, Zhao Wang, Dayong Huang, Zhongxia Huang, Xiaoxiong Wu, Xiaohong Li, Fang Ye, Fan Yu, Hui Liu, Jing-Wen Wang, Jia Cong, Wanjun Sun, Hui-Ren Chen, Jingbo Wang, Bing Han
Nowadays, the regular recommended dose of decitabine for the treatment of myelodysplastic syndrome (MDS) is 20 mg/m2/day for 5 consecutive days with a relatively high incidence of treatment-related morbidities and costs. In this study, a retrospective and multicenter analysis was performed to explore the very-low-dose decitabine schedule for the treatment of patients with IPSS intermediate- or high-risk MDS. A total of 31 newly diagnosed MDS cases from 14 hospitals in Beijing received decitabine monotherapy (decitabine 6 mg/m2/day intravenously for 7 consecutive days, repeated every 4 weeks)...
October 19, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/29043875/consolidation-therapy-with-decitabine-and-intermediate-dose-cytarabine-followed-by-hla-mismatched-peripheral-blood-stem-cells-infusion-for-older-patients-with-acute-myeloid-leukemia-in-first-remission
#16
Wei-Yang Li, Ying Wang, Su-Ning Chen, Hui-Ying Qiu, Zheng-Zheng Fu, De-Pei Wu, Ai-Ning Sun
This retrospective study tested the feasibility of decitabine (DAC) plus intermediate-dose cytarabine (ID-AraC) followed by HLA-mismatched granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral donor blood stem cells (GPBSCs) infusion as consolidation treatment for older patients with acute myeloid leukemia (AML) in first complete remission (CR). A total of 23 patients received this regimen for 3 cycles (D-GPBSCs group), and the outcome was compared with that of 19 patients treated with repeated cycles of ID-AraC chemotherapy (chemo group)...
October 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29042320/bone-targeting-nanoparticle-to-co-deliver-decitabine-and-arsenic-trioxide-for-effective-therapy-of-myelodysplastic-syndrome-with-low-systemic-toxicity
#17
Xiaoyan Wu, Zhenhua Hu, Sara Nizzero, Guodong Zhang, Maricela R Ramirez, Ce Shi, Jin Zhou, Mauro Ferrari, Haifa Shen
Myelodysplastic syndromes (MDS) are a diverse group of bone marrow disorders and clonal hematopoietic stem cell disorders characterized by abnormal blood cells, or reduced peripheral blood cell count. Recent clinical studies on combination therapy of decitabine (DAC) and arsenic trioxide (ATO) have demonstrated synergy on MDS treatment, but the treatment can cause significant side effects to patients. In addition, both drugs have to be administered on a daily basis due to their short half-lives. In addressing key issues of reducing toxic side effects and improving pharmacokinetic profiles of the therapeutic agents, we have developed a new formulation by co-packaging DAC and ATO into alendronate-conjugated bone-targeting nanoparticles (BTNPs)...
October 16, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29034009/a-multicenter-randomized-study-of-decitabine-as-epigenetic-priming-with-induction-chemotherapy-in-children-with-aml
#18
Lia Gore, Timothy J Triche, Jason E Farrar, Daniel Wai, Christophe Legendre, Gerald C Gooden, Winnie S Liang, John Carpten, David Lee, Frank Alvaro, Margaret E Macy, Carola Arndt, Philip Barnette, Todd Cooper, Laura Martin, Aru Narendran, Jessica Pollard, Soheil Meshinchi, Jessica Boklan, Robert J Arceci, Bodour Salhia
BACKGROUND: Decitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases, which has been studied extensively and is approved for myelodysplastic syndrome in adults but with less focus in children. Accordingly, we conducted a phase 1 multicenter, randomized, open-label study to evaluate decitabine pre-treatment before standard induction therapy in children with newly diagnosed AML to assess safety and tolerability and explore a number of biologic endpoints. RESULTS: Twenty-four patients were fully assessable for all study objectives per protocol (10 in Arm A = epigenetic priming induction, 14 in Arm B = standard induction)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29029492/gata2-regulates-the-erythropoietin-receptor-in-t-12-21-all
#19
Marie E Gaine, Daniel J Sharpe, James S Smith, Hilary A A Colyer, Vivien M Hodges, Terry R Lappin, Ken I Mills
The t(12;21) (p13;q22) chromosomal translocation resulting in the ETV6/RUNX1 fusion gene is the most frequent structural cytogenetic abnormality in children with acute lymphoblastic leukemia (ALL). The erythropoietin receptor (EPOR), usually associated with erythroid progenitor cells, is highly expressed in ETV6/RUNX1 positive cases compared to other B-lineage ALL subtypes. Gene expression analysis of a microarray database and direct quantitative analysis of patient samples revealed strong correlation between EPOR and GATA2 expression in ALL, and higher expression of GATA2 in t(12;21) patients...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28976600/midostaurin-a-new-oral-agent-targeting-flt3-mutant-acute-myeloid-leukemia
#20
Lindsay C Stansfield, Daniel A Pollyea
Acute myeloid leukemia (AML), a clonal hematologic malignancy that results in bone marrow failure, is the most common acute leukemia in adults (median age of diagnosis 67 years), and treatment options, especially in the elderly population, are limited. Induction chemotherapy with 7+3, the combination of continuous-infusion cytarabine and intermittent dosing of an anthracycline administered over 7 and 3 days, respectively, has remained the standard of care since its introduction in 1973 in the United States...
October 4, 2017: Pharmacotherapy
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