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https://www.readbyqxmd.com/read/28944397/chronic-myeloid-leukemia-the-promise-of-tyrosine-kinase-inhibitor-discontinuation
#1
REVIEW
Ravi Kishore Narra, Kathryn E Flynn, Ehab Atallah
Some believe that tyrosine kinase inhibitor (TKI) therapy is as close to perfect as it gets in oncologic therapy. Patients diagnosed with chronic myeloid leukemia (CML) are treated with a daily oral therapy, through which most achieve remission. TKI therapy is not associated with classic chemotherapy side effects, and most patients are able to resume their normal activities of daily living. Moreover, recent data has demonstrated that CML does not affect the life expectancy of patients whose disease is well controlled with a TKI...
September 25, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28942039/comparative-effect-of-imatinib-and-ponatinib-on-autophagy-and-mirnome-in-chronic-myeloid-leukemia
#2
Cagla Kayabasi, Tugce Balci Okcanoglu, Besra Ozmen Yelken, Aycan Asik, Sunde Yilmaz Susluer, Cigir Biray Avci, Guray Saydam, Cumhur Gunduz
BCR-ABL tyrosine kinase inhibitors (TKIs) are selective therapies for the patients with Chronic Myeloid Leukemia (CML). Imatinib and ponatinib have remarkable long-term efficacy on a major molecular response. Although TKI related induction of cytotoxicity and apoptosis have been clearly investigated in molecular levels, their comparative effect on autophagy and miRNome are largely unknown. This study aimed to investigate the involvement of alterations of miRNA expressions in CML progression, and how imatinib and ponatinib affect this process, by comparing CML, imatinib-resistant CML and leukemia stem cells (LSC)...
September 20, 2017: Gene
https://www.readbyqxmd.com/read/28939746/phase-iii-clinical-trial-rerise-study-results-of-efficacy-and-safety-of-radotinib-compared-with-imatinib-in-newly-diagnosed-chronic-phase-chronic-myeloid-leukemia
#3
Jae Yong Kwak, Sung-Hyun Kim, Suk Joong Oh, Dae Young Zang, Hawk Kim, Jeong-A Kim, Young Rok Do, Hyeoung-Joon Kim, Joon Seong Park, Chul Won Choi, Won-Sik Lee, Yeung-Chul Mun, Jee Hyun Kong, Joo-Seop Chung, Ho Jin Shin, Dae-Young Kim, Jinny Park, Chul Won Jung, Udomask Bunworasate, Narcisa Sonia Comia, Saengsuree Jootar, Harryanto Reksodiputro, Priscilla B Caguioa, Sung-Eun Lee, Dong-Wook Kim
PURPOSE: Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for CML-CP in patients newly diagnosed or with insufficient response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP. METHODS: This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily (bid) radotinib doses, or imatinib daily (qd). The primary endpoint was major molecular response (MMR) by 12 months...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28936999/non-adherence-to-cml-therapy-and-its-clinical-implications-in-india
#4
REVIEW
Hari Menon
Clinical trials have shown that early and deeper cytogenetic/ molecular responses to tyrosine kinase inhibitors (TKIs) help in achieving improved long-term outcomes including lower rates of disease progression in chronic myeloid leukaemia (CML). However, the level of molecular responses achieved with TKI therapy in patients with CML is variable and this could be explained by differences in adherence to CML therapy. A systematic literature review of CML studies reporting adherence to BCR-ABL inhibitors from the USA, Asia and Europe (19 articles: 9 retrospective, 4 prospective, rest cross-sectional) showed that average adherence varies from 19% to 100% of the proportion of prescribed drug taken...
May 2017: National Medical Journal of India
https://www.readbyqxmd.com/read/28936634/jsh-guideline-for-tumors-of-hematopoietic-and-lymphoid-tissues-lukemia-4-chronic-myelogenous-leukemia-cml-myeloproliferative-neoplasms-mpn
#5
Noriko Usui
No abstract text is available yet for this article.
September 21, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28933312/characterization-of-imatinib-resistant-cml-leukemic-stem-initiating-cells-and-their-sensitivity-to-cbp-catenin-antagonists
#6
Yi Zhao, Kaijin Wu, Yongfeng Wu, Elizabeth Melendez, Goar Smbatyan, David Massiello, Michael Kahn
The development of the tyrosine kinase inhibitor Imatinib (IM) represents a milestone breakthrough in CML (Chronic Myeloid Leukemia) treatment. However, it is not curative and patients develop IM resistance. IM resistance has been previously correlated with the emergence of drug-resistant LIC/LSC (Leukemia Initiating Cell/Leukemia Stem Cell) and increased nuclear catenin levels and enhanced Wnt signaling. It has been demonstrated previously that drug resistant CML LIC/LSC can be safely eliminated both in vitro and in vivo via disruption of the CBP/catenin interaction, utilizing the highly biochemically selective small molecule CBP/catenin antagonist ICG-001...
September 19, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28931089/advanced-glycation-end-products-dietary-restriction-effects-on-bacterial-gut-microbiota-in-peritoneal-dialysis-patients-a-randomized-open-label-controlled-trial
#7
Rabi Yacoub, Melinda Nugent, Weijin Cai, Girish N Nadkarni, Lee D Chaves, Sham Abyad, Amanda M Honan, Shruthi A Thomas, Wei Zheng, Sujith A Valiyaparambil, Mark A Bryniarski, Yijun Sun, Michael Buck, Robert J Genco, Richard J Quigg, John C He, Jaime Uribarri
The modern Western diet is rich in advanced glycation end products (AGEs). We have previously shown an association between dietary AGEs and markers of inflammation and oxidative stress in a population of end stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD). In the current pilot study we explored the effects of dietary AGEs on the gut bacterial microbiota composition in similar patients. AGEs play an important role in the development and progression of cardiovascular (CVD) disease. Plasma concentrations of different bacterial products have been shown to predict the risk of incident major adverse CVD events independently of traditional CVD risk factors, and experimental animal models indicates a possible role AGEs might have on the gut microbiota population...
2017: PloS One
https://www.readbyqxmd.com/read/28930482/diagnostic-and-prognostic-cytogenetics-of-chronic-myeloid-leukaemia-an-update
#8
Matteo Molica, Fulvio Massaro, Massimo Breccia
Despite the advent of molecular assessment, banding cytogenetics and fluorescence in situ hybridization (FISH) still have a significant role in diagnostic and prognostic approaches to chronic myeloid leukaemia (CML). Area covered. At diagnosis and duringtreatment with tyrosine kinase inhibitors (TKIs), cytogenetics is used to detect the Philadelphia chromosome, with its typical translocation t(9;22)(q34;q11.2), and any additional or other chromosomal aberrations (ACAs and OCAs) that may arise in 5-10% of cases, the latter associated to transformation of the disease in blast phases...
September 20, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28929332/deeper-molecular-response-is-a-predictive-factor-for-treatment-free-remission-after-imatinib-discontinuation-in-patients-with-chronic-phase-chronic-myeloid-leukemia-the-jalsg-stim213-study
#9
Naoto Takahashi, Tetsuzo Tauchi, Kunio Kitamura, Koichi Miyamura, Yoshio Saburi, Yoshihiro Hatta, Yasuhiko Miyata, Shinichi Kobayashi, Kensuke Usuki, Itaru Matsumura, Yosuke Minami, Noriko Usui, Tetsuya Fukuda, Satoru Takada, Maho Ishikawa, Katsumichi Fujimaki, Hiroshi Gomyo, Osamu Sasaki, Kohshi Ohishi, Takaaki Miyake, Kiyotoshi Imai, Hitoshi Suzushima, Hideki Mitsui, Kazuto Togitani, Toru Kiguchi, Yoshiko Atsuta, Shigeki Ohtake, Kazunori Ohnishi, Yukio Kobayashi, Hitoshi Kiyoi, Yasushi Miyazaki, Tomoki Naoe
The objective of this prospective clinical trial (JALSG-STIM213, UMIN000011971) was to evaluate treatment-free remission (TFR) rates after discontinuation of imatinib in chronic myeloid leukemia (CML). CML patients who received imatinib treatment for at least 3 years and sustained deep molecular response for at least 2 years were eligible. Molecular recurrence was defined as loss of major molecular response (MMR). Of the 68 eligible patients, 38.2% were women, the median age was 55.0 years, and the median duration of imatinib treatment was 97...
September 19, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28928866/ct-721-a-potent-bcr-abl-inhibitor-exhibits-excellent-in-vitro-and-in-vivo-efficacy-in-the-treatment-of-chronic-myeloid-leukemia
#10
Yinghui Sun, Na Zhao, Huan Wang, Qiong Wu, Yunqi Han, Qichao Liu, Mangang Wu, Yuliang Liu, Fansheng Kong, He Wang, Ying Sun, Deguang Sun, Lutao Jing, Guojing Tang, Yuandong Hu, Dengming Xiao, Hong Luo, Yongxin Han, Yong Peng
Kinase inhibitors that target Bcr-Abl are highly effective in the treatment of chronic myeloid leukemia (CML). However, these inhibitors are often invalidated due to the drug resistance. Therefore, the discovery and development of novel Bcr-Abl inhibitors is required to overwhelm the drug resistance in the treatment of CML resistant to the currently used first-line Bcr-Abl inhibitors. Herein we have described a newly developed Bcr-Abl inhibitor CT-721, which displayed potent inhibitory effects on wild-type and T315I mutant Bcr-Abl...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928163/high-bcr-abl-gusis-levels-at-diagnosis-of-chronic-phase-cml-are-associated-with-unfavorable-responses-to-standard-dose-imatinib
#11
Paolo Vigneri, Fabio Stagno, Stefania Stella, Alessandra Cupri, Stefano Forte, Michele Massimino, Agostino Antolino, Sergio Siragusa, Donato Mannina, Stefana S Impera, Caterina Musolino, Alessandra Malato, Giuseppe Mineo, Carmela Tomaselli, Pamela Murgano, Maurizio Musso, Fortunato Morabito, Stefano Molica, Bruno Martino, Livia Manzella, Martin C Müller, Andreas Hochhaus, Francesco Di Raimondo
PURPOSE: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate Imatinib responses. EXPERIMENTAL DESIGN: We correlated BCR-ABL/GUSIS and BCR-ABL/ABLIS transcripts at diagnosis with the outcome - defined by the 2013 European LeukemiaNet recommendations - of 272 newly diagnosed CML patients receiving Imatinib 400 mg/daily...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28926475/altered-resting-state-functional-connectivity-of-default-mode-network-and-sensorimotor-network-in-heavy-metal-music-lovers
#12
Yan Sun, Congcong Zhang, Shuxia Duan, Xiaoxia Du, Vince D Calhoun
The aim of this study was to investigate the spontaneous neural activity and functional connectivity (FC) in heavy metal music lovers (HMML) compared with classical music lovers (CML) during resting state. Forty HMML and 31 CML underwent resting-state functional MRI scans. Fractional amplitude of low-frequency fluctuations (fALFF) and seed-based resting-state FC were computed to explore regional activity and functional integration. A voxel-based two-sample t-test was used to test the differences between the two groups...
September 18, 2017: Neuroreport
https://www.readbyqxmd.com/read/28920959/targeting-mitochondrial-oxidative-phosphorylation-eradicates-therapy-resistant-chronic-myeloid-leukemia-stem-cells
#13
Elodie M Kuntz, Pablo Baquero, Alison M Michie, Karen Dunn, Saverio Tardito, Tessa L Holyoake, G Vignir Helgason, Eyal Gottlieb
Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second- and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically. Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner, we searched for such vulnerabilities in CML LSCs...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28919910/chloroma-of-the-testis-in-a-patient-with-a-history-of-acute-myeloid-leukemia
#14
Mohammad Hossein Sanei, Matin Shariati
Chloroma, or granulocytic sarcoma, is a rare extramedullary solid hematologic cancer, found concomitant with acute myeloid leukemia. It is infrequently associated with other myeloproliferative disorders or chronic myelogenous leukemia. Chloroma of the testis after allogeneic bone marrow transplantation is particularly sparsely represented in the literature. It is suggested that an appropriate panel of marker studies be performed along with clinical correlation and circumspection to avoid misleading conclusions...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/28919770/swollen-lymph-nodes-may-not-be-clinical-manifestations-of-chronic-myeloid-leukemia-case-report-and-revision-of-literature
#15
Zhihe Liu, Siyun Li, Ou Bai
We present here the case of a 33-year-old Chinese female patient with synchronous double primary malignant tumors (chronic myeloid leukemia [CML] and classic Hodgkin lymphoma). This patient was admitted to our hospital because of bilateral cervical lymph node enlargement and recurrent fever for 2 weeks. The complete blood cell count revealed white blood cell counts of 18.2×10(9)/L, hemoglobin of 9.6 g/dL, and platelet counts of 1,547×10(9)/L. Chromosome karyotype analysis demonstrated that t(9;22)(q34;q11) was positive in all 20 cells examined...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28916568/perspective-the-paradox-in-dietary-advanced-glycation-end-products-research-the-source-of-the-serum-and-urinary-advanced-glycation-end-products-is-the-intestines-not-the-food
#16
Luanne R DeChristopher
Inconsistent research results have impeded our understanding of the degree to which dietary advanced glycation end products (dAGEs) contribute to chronic disease. Early research suggested that Western-style fast foods, including grilled and broiled meats and French fries, contain high levels of proinflammatory advanced glycation end products (AGEs). However, recent studies with state-of-the-art ultraperformance LC-tandem mass spectrometry (UPLC-MS) found that there is no evidence that these foods have elevated levels of dAGEs relative to other foods...
September 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28905936/combing-oncolytic-adenovirus-expressing-beclin-1-with-chemotherapy-agent-doxorubicin-synergistically-enhances-cytotoxicity-in-human-cml-cells-in-vitro
#17
Li Li, Liang-Shun You, Li-Ping Mao, Shen-He Jin, Xiao-Hui Chen, Wen-Bin Qian
Cancer virotherapy provides a new strategy to treat cancer that can directly kill cancer cells by oncolysis. Insertion of therapeutic genes into the genome of a modified adenovirus, thereby creating a so-called gene-virotherapy that shares the advantages of gene therapy and virotherapy. In this study we investigated whether a strategy that combines the oncolytic effects of an adenoviral vector with the simultaneous expression of the autophagy gene Beclin-1 offered a therapeutic advantage for chronic myeloid leukemia (CML) cells with resistance to chemotherapy and evaluated the synergistic effects of SG511-BECN and doxorubicin (Dox) in human CML cells in vitro...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28905209/expression-differences-of-genes-in-the-pi3k-akt-wnt-b-catenin-shh-notch-and-mapk-signaling-pathways-in-cd34-hematopoietic-cells-obtained-from-chronic-phase-patients-with-chronic-myeloid-leukemia-and-from-healthy-controls
#18
R de Cássia Viu Carrara, A M Fontes, K J Abraham, M D Orellana, S K Haddad, P V B Palma, R A Panepucci, M A Zago, D T Covas
PURPOSE: The fusion gene BRC-ABL has an important role to the progression of chronic myeloid leukemia (CML) and several signaling pathways have been characterized as responsible for the terminal blastic phase (BP). However, the initial phase, the chronic phase (CP), is long lasting and there is much yet to be understood about the critical role of BRC-ABL in this phase. This study aims to evaluate transcriptional deregulation in CD34+ hematopoietic cells (CD34+ cells) from patients with untreated newly diagnosed CML compared with CD34+HC from healthy controls...
September 13, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28902850/copy-number-variation-analysis-in-cytochromes-and-glutathione-s-transferases-may-predict-efficacy-of-tyrosine-kinase-inhibitors-in-chronic-myeloid-leukemia
#19
Alexander V Lavrov, Oksana A Ustaeva, Elmira P Adilgereeva, Svetlana A Smirnikhina, Ekaterina Y Chelysheva, Oleg A Shukhov, Yuriy V Shatokhin, Sergey V Mordanov, Anna G Turkina, Sergey I Kutsev
Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the presence of BCR/ABL fusion gene in leukemic cells, which promotes uncontrolled cell proliferation. Up to 20% of CML patients show primary resistance or non-optimal response to tyrosine kinase inhibitor (TKI) therapy. We investigated the association between copy number variation (CNV) in glutathione S-transferases (GST) and cytochromes (CYP) and the response rate to TKI. We enrolled 47 patients with CML: 31 with an optimal response and 16 with failure at 6 months in accordance with European LeukemiaNet 2013 recommendations...
2017: PloS One
https://www.readbyqxmd.com/read/28901467/aberrantly-expressed-transcription-factors-c-ebp-and-sox4-have-positive-effects-in-the-development-of-chronic-myeloid-leukemia
#20
Fei Dong, Guili Zhang, Xia Zhang, Xuena Liu, Na Wang, Chengming Sun
The aim of the present study was to examine the expression and significance of CCAAT/enhancer binding protein α (C/EBPα) and SRY‑related high mobility group box containing transcription factor 4 (SOX4) in chronic myeloid leukemia (CML). Bone marrow samples were collected from patients with CML, and peripheral blood mononuclear cells were collected from healthy controls. Protein and mRNA were extracted from the collected samples, and analyzed using western blotting and reverse transcription‑quantitative polymerase chain reaction analyses, respectively...
September 13, 2017: Molecular Medicine Reports
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