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https://www.readbyqxmd.com/read/27905102/elevated-fetal-haemoglobin-is-a-predictor-of-better-outcome-in%C3%A2-mds-aml-patients-receiving-5-aza-2-deoxycytidine-decitabine
#1
Michael Lübbert, Gabriele Ihorst, Philipp N Sander, Ljudmila Bogatyreva, Heiko Becker, Pierre W Wijermans, Stefan Suciu, Emmanuel Bissé, Rainer Claus
Although azanucleoside DNA-hypomethylating agents (HMAs) are routinely used for the treatment of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), very few outcome predictors have been established. Expression of the β-like globin gene locus is tightly regulated by DNA methylation, is HMA-sensitive in vitro, and fetal haemoglobin (HbF) expression is under study as a potential biomarker for response of MDS patients to azacitidine. We determined HbF expression in 16 MDS and 36 AML patients receiving decitabine (DAC)...
December 1, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27873493/decitabine-as-a-first-line-treatment-for-older-adults-newly-diagnosed-with-acute-myeloid-leukemia
#2
Hyunsung Park, Haerim Chung, Jungyeon Lee, Jieun Jang, Yundeok Kim, Soo Jeong Kim, Jin Seok Kim, Yoo Hong Min, June Won Cheong
PURPOSE: Decitabine, a DNA hypomethylating agent, was recently approved for use in Korea for older adults with acute myeloid leukemia (AML) who are not candidates for standard chemotherapy. This study aimed to evaluate the role of decitabine as a first-line treatment for older adults with AML. MATERIALS AND METHODS: Twenty-four patients with AML who received at least one course of decitabine (20 mg/m²/d intravenously for 5 days every 4 weeks) as a first-line therapy at Severance Hospital were evaluated retrospectively...
January 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/27849645/current-management-of-patients-with-chronic-myelomonocytic-leukemia
#3
Ana Alfonso, Guillermo Montalban-Bravo, Guillermo Garcia-Manero
PURPOSE OF REVIEW: The present review will focus on the current management of patients with chronic myelomonocytic leukemia (CMML) as well as in future therapeutic perspectives. RECENT FINDINGS: CMML is a clonal hematopoietic stem cell disorder characterized by peripheral blood monocytosis and myelodysplastic and myeloproliferative alterations in the bone marrow. Clinical behavior of the disease can be heterogeneous, with some patients having an indolent form of the disease, whereas others experience an aggressive course with decreased survival and eventual transformation to leukemia...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27835920/-acute-myeloid-leukemia
#4
Jan Braess
Acute myeloid leukemia (AML) has been genetically characterized extensively and can now be subdivided into 9 to 11 pathogenetically different subtypes according to their profile of driver mutations. In clinical practice karyotyping and molecular analysis of NPM1, cEBPa and FLT3-ITD are required for treatment stratification and potentially genotype specific treatment. Some markers such as NPM1 not only offer prognostic information but can also serve as markers of minimal residual disease and thus have the potential to guide therapy in the future...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27812249/the-synergistic-effects-of-decitabine-combined-with-arsenic-trioxide-ato-in-the-human-myelodysplastic-syndrome-cell-line-skm-1
#5
Ping Wu, Long Liu, Jianyu Weng, Suxia Geng, Chengxin Deng, Zesheng Lu, Chengwei Luo, Xin Du
Despite recent advances in the treatment of myelodysplastic syndrome (MDS), single-agent clinical effects remain unsatisfactory, and decitabine monotherapy is also associated with a relatively low rate of complete remission. To study the combined effects and mechanism of decitabine (DAC) and arsenic trioxide (ATO) on the human myelodysplastic cell line SKM-1,we used the MTS assay and CalcuSyn software to determine the cytotoxicity and potential synergistic effects, respectively. Furthermore, we determined apoptosis and measured the mRNA expression level of two genes that are considered main regulators of the apoptosis process...
December 2016: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/27808592/pd1-and-pdl1-upregulation-and-survival-after-decitabine-treatment-in-lower-risk-mds
#6
Sameem Abedin, Leonidas C Platanias
No abstract text is available yet for this article.
November 3, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27801319/-analysis-of-the-impact-of-decitabine-treatment-cycles-on-efficacy-and-safety-in-patients-of-myelodysplastic-syndrome-refractory-anemia-with-excess-blasts
#7
X P Luo, Z F Xu, T J Qin, Y Zhang, H L Zhang, L W Fang, L J Pan, N B Hu, S Q Qu, B Li, Z J Xiao
Objective: To explore the impact of decitabine treatment cycles on efficacy and adverse events(AEs)in patients of myelodysplastic syndrome-refractory anemia with excess blasts(MDSRAEB). Methods: A total of fifty-six patients with MDS-RAEB who received decitabine 20 mg·m(-2)·d(-1)by IV infusion daily for 5 consecutive days every 4 weeks at a single institute in China were enrolled from December 2008 to March 2016. Their clinical features, efficacy, predictors of efficacy and AEs were analyzed retrospectively...
October 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27784379/-clinical-comparation-of-two-kinds-of-chemotherapy-regimen-in-the-treatment-of-elderly-mds-patients-with-aml-transformed-by-abnormal-proliferation-of-bone-marrow
#8
Zhong-Hao Zhou, Xiao-Hong Zhao, Shi-Yun Lu, Chen Wang, Zhi Wang
OBJECTIVE: To investigate the clinical efficacy and safety of "3+7" regimen and decitabine + HAG pre-excitation regimen in the treatment of elderly MDS patients with AML transformed by abnormal proliferation of bone marrow. METHODS: Fifty elderly patients with AML transformed by abnormal proliferation of bone marrow in the period from March 2012 to May 2014 were chosen and randomly divided into 2 groups including A group (25 elderly patients treated with "3+7" regimen) and B group (25 elderly patients treated with decitabine+HAG pre-excitation regimen), and the clinical effeicacy, the median survival time and the incidence of drug adverse effects in 2 groups were compared...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27784354/-effect-of-decitabine-in-combination-with-arsenic-trioxide-on-prolife-ration-and-apoptosis-of-human-acute-myeloid-leukemia-mv4-11-cells
#9
Si-Si Chen, Yan-Ping Zhao, Wen-Zhong Wu, Tie-Liang Ma, Su-Ning Chen
OBJECTIVE: To investigate the effect of decitabine (DAC) alone or in combination with arsenic trioxide (As2O3) on the proliferation and apoptosis of human acute myeloid leukemia (AML) MV4-11 cells, so as to find an effective method for treating AML with MLL rearrangements. METHODS: The inhibitory effect of DAC and As2O3 alone, as well as in a combination of less than 50% inhibitory concentration (IC50) of DAC, and with less than 20% inhibitory concentration (IC20) As2O3 on MV4-11 cell proliferation were detected by CCK-8 methed; and the apoptosis inducing effect was determined by flow cytometry...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27784352/-clinical-efficacy-of-decitabine-combined-with-modified-cag-regimen-for-relapse-refractory-acute-myeloid-leukemia-with-aml1-eto
#10
Qiang Liu, Xiao-Ming Fei
OBJECTIVE: To investigate the clinical characteristics of patients with relapse-refractory acute myeloid leukemia(AML) with AML1-ETO(+), and therapeutic effcacy and side effects of decitabine combined with modified CAG regimen. METHODS: Clinical data of 8 cases of AML with AML1-ETO(+) from June 2015 to January 2016 were analyzed retrospectively, including age, sex, initial symptoms, peripheral blood and bone marrow characteristics and so on. at the same time, the therapeutic effcacy and side effects of decitabine combined with modified CAG regimen were evaluated...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27774847/differential-response-to-hypomethylating-agents-based-on-sex-a-report-on-behalf-of-the-mds-clinical-research-consortium-mds-crc
#11
Amy E DeZern, Amer M Zeidan, John Barnard, Wesley Hand, Najla Al Ali, Francis Brown, Cassie Zimmerman, Gail J Roboz, Guillermo Garcia-Manero, David P Steensma, Rami S Komrokji, Mikkael A Sekeres
First-line therapy for higher-risk myelodysplastic syndromes (MDS) includes decitabine (DAC) or azacitidine (AZA). Variables have not identified differential response rates between these. We assessed the influence of patient sex on outcomes including overall survival (OS) in 642 patients with higher-risk MDS treated with AZA or DAC. DAC-treated patients (35% of females, 31% of males) had marginally better OS than AZA-treated patients (p = .043), (median OS of 18.7 months versus 16.4 months), but the difference varied strongly by sex...
October 24, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27770540/a-minicircuitry-of-microrna-9-1-and-runx1-runx1t1-contributes-to-leukemogenesis-in-t-8-21-acute-myeloid-leukemia
#12
Lin Fu, Jinlong Shi, Anqi Liu, Lei Zhou, Mengmeng Jiang, Huaping Fu, Keman Xu, Dandan Li, Ailing Deng, Qingyi Zhang, Yifan Pang, Yujie Guo, Kai Hu, Jiansuo Zhou, Yapeng Wang, Wenrong Huang, Yu Jing, Liping Dou, Lili Wang, Kailin Xu, Xiaoyan Ke, Clara Nervi, Yonghui Li, Li Yu
MicroRNA-9-1(miR-9-1) plays an important role in the mechanism that regulates the lineage fate of differentiating hematopoietic cells. Recent studies have shown that miR-9-1 is downregulated in t (8; 21) AML. However, the pathogenic mechanisms underlying miR-9-1 down-regulation and the RUNX1-RUNX1T1 fusion protein, generated from the translocation of t (8; 21) in AML, remain unclear. RUNX1-RUNX1T1 can induce leukemogenesis through resides in and functions as a stable RUNX1-RUNX1T1-containing transcription factor complex...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27765068/genome-wide-methylation-profiling-of-ovarian-cancer-patient-derived-xenografts-treated-with-the-demethylating-agent-decitabine-identifies-novel-epigenetically-regulated-genes-and-pathways
#13
Tushar Tomar, Steven de Jong, Nicolette G Alkema, Rieks L Hoekman, Gert Jan Meersma, Harry G Klip, Ate Gj van der Zee, G Bea A Wisman
BACKGROUND: In high-grade serous ovarian cancer (HGSOC), intrinsic and/or acquired resistance against platinum-containing chemotherapy is a major obstacle for successful treatment. A low frequency of somatic mutations but frequent epigenetic alterations, including DNA methylation in HGSOC tumors, presents the cancer epigenome as a relevant target for innovative therapy. Patient-derived xenografts (PDXs) supposedly are good preclinical models for identifying novel drug targets. However, the representativeness of global methylation status of HGSOC PDXs compared to their original tumors has not been evaluated so far...
October 20, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27745715/selecting-initial-treatment-of-acute-myeloid-leukaemia-in-older-adults
#14
Nikolai A Podoltsev, Maximilian Stahl, Amer M Zeidan, Steven D Gore
More than half of the patients with acute myeloid leukaemia (AML) are older than 60years. The treatment outcomes in this group remain poor with a median overall survival of <1year. Selecting initial treatment for these patients involves an assessment of 'fitness' for induction chemotherapy. This is done based on patient and disease-related characteristics which help to estimate treatment-related mortality and chance of complete remission with induction chemotherapy. If the risk of treatment-related mortality is high and/or the likelihood of a patient achieving a complete remission is low, lower-intensity treatment (low-dose cytarabine, decitabine and azacitidine) should be discussed...
October 8, 2016: Blood Reviews
https://www.readbyqxmd.com/read/27740633/dynamic-changes-in-the-clonal-structure-of-mds-and-aml-in-response-to-epigenetic-therapy
#15
G L Uy, E J Duncavage, G S Chang, M A Jacoby, C A Miller, J Shao, S Heath, K Elliott, T Reinick, R S Fulton, C C Fronick, M O'Laughlin, L Ganel, C N Abboud, A F Cashen, J F DiPersio, R K Wilson, D C Link, J S Welch, T J Ley, T A Graubert, P Westervelt, M J Walter
Traditional response criteria in MDS and AML are based on bone marrow morphology and may not accurately reflect clonal tumor burden in patients treated with non-cytotoxic chemotherapy. We used next-generation sequencing of serial bone marrow samples to monitor MDS and AML tumor burden during treatment with epigenetic therapy (decitabine and panobinostat). Serial bone marrow samples (and skin as a source of normal DNA) from 25 MDS and AML patients were sequenced (exome or 285 gene panel). We observed that responders, including those in complete remission (CR), can have persistent measurable tumor burden (i...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27738797/impact-of-antibacterial-prophylaxis-during-reinduction-chemotherapy-for-relapse-refractory-acute-myeloid-leukemia
#16
Beejal R Ganti, Bernard L Marini, Jerod Nagel, Dale Bixby, Anthony J Perissinotti
PURPOSE: This study evaluated the impact of antibacterial prophylaxis with levofloxacin in relapsed/refractory acute myeloid leukemia (AML) patients. METHODS: This was a retrospective, single-center, cohort study. Adult patients with relapsed/refractory AML admitted for reinduction chemotherapy between November 1, 2006 and June 15, 2015 were screened for inclusion. A protocol initiating levofloxacin prophylaxis was implemented on December 1, 2013. Patients receiving hypomethylating agents (decitabine/azacitidine) were not administered antibacterial prophylaxis and thus not included in this analysis...
October 14, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/27719724/-effects-of-dna-methylation-on-abo-gene-expression-in-leukemia
#17
M Shao, X P Lyu, Q K Yang, W T Zhu, J Song, Y K Kong, J Wang, L Sun, F Wang
Objective: To investigate the impact of promoter CpG island methylation on ABO mRNA expression in leukemia. Methods: 25 cases of leukemia and 20 cases of normal control were studied, and the leukemia cell lines K562、HL-60 and Jurkat were treated with different concentrations of decitabine. PCR-SSP was used to identify ABO genotype, RQ-PCR for ABO mRNA expression and bisulfite sequencing PCR for DNA methylation status. Results: ① The methylation of ABO promoter in acute myeloid leukemia patients (10 cases) and acute lymphoblastic leukemia patients (10 cases) were 53...
September 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27686004/increased-pd-1-stat1-ratio-may-account-for-the-survival-benefit-in-decitabine-therapy-for-lower-risk-myelodysplastic-syndrome
#18
Zheng Zhang, Chun-Kang Chang, Qi He, Juan Guo, Ying Tao, Ling-Yun Wu, Feng Xu, Dong Wu, Li-Yu Zhou, Ji-Ying Su, Lu-Xi Song, Chao Xiao, Xiao Li
Decitabine is an effective therapy for patients with lower risk myelodysplastic syndrome (MDS). However, the mechanisms of decitabine's therapeutic effect are not well established. Forty-four lower risk MDS patients received decitabine therapy. 59.1% patients achieved treatment response, and 53.8% patients who were RBC/platelet-dependent cast off the transfusion burden. The median overall survival (OS) was 19.0 months after decitabine treatment. Moreover, polarization toward type 1 in the CD8 + subset was enhanced, and a significantly increased expression of the PD-1, PD-L1, and PD-1/STAT1 ratio was observed in these lower risk MDS...
August 11, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27685787/decitabine-and-5-azacitidine-both-alleviate-lps-induced-ards-through-anti-inflammatory-antioxidant-activity-and-protection-of-glycocalyx-and-inhibition-of-mapk-pathways-in-mice
#19
Xiao Huang, Guiqing Kong, Yan Li, Weiwei Zhu, Haixiao Xu, Xiaohua Zhang, Jiankui Li, Lipeng Wang, Zhongwen Zhang, Yaru Wu, Xiangyong Liu, Xiaozhi Wang
Decitabine (5-aza-2'-deoxycytidine, DAC) and 5-azacitidine (Aza), an inhibitor of DNA methyltransferases, possess a wide range of anti-metabolic and anti-cancer activities. This study examined the effects of DAC and Aza on inflammatory and oxidative injuries, as well as on glycocalyx and MAPK signaling pathways, in a LPS-stimulated ARDS mouse model. Results of ELISA revealed that DAC and Aza significantly inhibited the production of TNF-α and IL-1β and prevented LPS-induced elevation of myeloperoxidase and malondialdehyde levels in serum...
September 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27671170/combination-treatment-with-decitabine-and-ionizing-radiation-enhances-tumor-cells-susceptibility-of-t-cells
#20
Cheol-Hun Son, Hong-Rae Lee, Eun-Kyoung Koh, Dong-Yeok Shin, Jae-Ho Bae, Kwangmo Yang, You-Soo Park
Decitabine has been found to have anti-metabolic and anti-tumor activities in various tumor cells. Recently, the use of decitabine in combination with other conventional therapies reportedly resulted in improved anti-tumor activity against various tumors. Ionizing radiation (IR) is widely used as a cancer treatment. Decitabine and IR improve immunogenicity and susceptibility of tumor cells to immune cells by up-regulating the expression of various molecules such as major histocompatibility complex (MHC) class I; natural-killer group 2, member D (NKG2D) ligands; and co-stimulatory molecules...
September 27, 2016: Scientific Reports
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