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Chronic myeloid leukemia

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https://www.readbyqxmd.com/read/28447248/somatic-setbp1-mutations-in-myeloid-neoplasms
#1
REVIEW
Hideki Makishima
SETBP1 is a SET-binding protein regulating self-renewal potential through HOXA-protein activation. Somatic SETBP1 mutations were identified by whole exome sequencing in several phenotypes of myelodysplastic/myeloproliferative neoplasms (MDS/MPN), including atypical chronic myeloid leukemia, chronic myelomonocytic leukemia, and juvenile myelomonocytic leukemia as well as in secondary acute myeloid leukemia (sAML). Surprisingly, its recurrent somatic activated mutations are located at the identical positions of germline mutations reported in congenital Schinzel-Giedion syndrome...
April 26, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28446318/-research-progress-of-homoharringtonine-effect-on-im-resistant-chronic-myelogenous-leukemia-review
#2
Qian Wang, Yu-Feng Li
Homoharringtonine(HHT) is an alkaloid with anti-tumor activity, having a good therapeutic effect on chronic myeloid leukemia(CML), and its toxicity is much lower than other anti-cancer drugs. However, the remarkable therapeutic efficacy of imatinib on CML treatment made HHT to be forgotten gradually. Today, the omacetaxine mepesuccinate, a semisynthetic form of HHT, display a good clinical response to TKI-resistant CML patients. Therefore, the HHT again attracts more attention from the medical field. Here, the clinical effects of HHT on IM-resistant CML patients and its mechanism are briefly reviewed...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446278/-clinical-analysis-for-42-imatinib-resistant-patients-with-chronic-myelogenous-leukemia
#3
Xi Liu, Si-Lin Gan, Jie Ma, Yan-Fang Liu, Xin-Sheng Xie, Zhong-Xing Jiang, Yuan-Dong Cheng, Hui Sun
OBJECTIVE: To analyze the kinase mutation ratio, related factors, effectiveness and safety of the second generation drugs for imatinib-resistant patients with chronic myeloid leukemia(CML). METHODS: COX proportional hazard regression model was used for unvariate and multvariate analysis of various factors affecting the kinase mutation and for evaluating the effectiveness and safety of second generation tyrosine kinase inhibitor(TKI). RESULTS: 13 kinds of mutation were detected in 19 out of 42 cases for 22 times, including 4 times of F359V, 3 times of E255K, 2 time for F359C, F317L, T315I, Y253H, 1 time for D256R, C250R, D276G, F486S, M244V, Y256H and G250E, 3 cases with mixed mutations...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446273/-effects-of-quercetin-on-chronic-myeloid-leukemia-cell-line-resistant-to-imatinib-and-its-mechanism
#4
Hong-Ying Lu, Juan Chen, Sheng-Hong DU, Pei-Min Jia, Jian-Hua Tong, Ying-Li Wu, Li Zhou
OBJECTIVE: To explore the growth inhibitory effect of quercetin on imatinib-resistant chronic myeloid leukemia cell lines and to clarify its involved mechanisms. METHODS: The cell viability was detected by trypan blue Staining, percentage of apoptotic cells and cell cycle distribution were detected by flow cytometry, the protein expression was detected by Western blot. RESULTS: Both inhibitory effect of proliferation and apoptosis-inducing effect were similar between the imatinib-resistant and -sensitive cell lines treated with 25 µmol/L quercetin for 24 hours and with arrest of cell cycle at G2/M phase...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28445830/overexpression-of-heme-oxygenase-1-in-bone-marrow-stromal-cells-promotes-microenvironment-mediated-imatinib-resistance-in-chronic-myeloid-leukemia
#5
Ping Liu, Dan Ma, Zhengyu Yu, Nana Zhe, Mei Ren, Ping Wang, Meisheng Yu, Jun Huang, Qin Fang, Jishi Wang
Neoplasm cells from patients with chronic myeloid leukemia (CML) interact with stromal cells of the surrounding microenvironment. Bone marrow stromal cells (BMSCs) represent the main population in CML marrow stroma, which may play a key role in disease support and progression. Heme oxygenase-1 (HO-1) is a key enzyme of antioxidative metabolism that is associated with cell proliferation and resistance to apoptosis. We herein up-regulated HO-1 expression of BMSCs and evaluated whether BMSCs influenced K562 cells survival...
April 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28444777/interphase-fish-for-bcr-abl1-rearrangement-on-neutrophils-a-decisive-tool-to-discriminate-a-lymphoid-blast-crisis-of-chronic-myeloid-leukemia-from-a-de-novo-bcr-abl1-positive-acute-lymphoblastic-leukemia
#6
Estelle Balducci, Marie Loosveld, Ilhem Rahal, John Boudjarane, Emilie Alazard, Chantal Missirian, Marina Lafage-Pochitaloff, Gérard Michel, Hélène Zattara
Discrimination between lymphoid blast crisis of chronic myeloid leukemia (CML) and de novo BCR-ABL1 positive acute lymphoblastic leukemia (ALL) represents a diagnostic challenge because this distinction has a major incidence on the management of patients. Here, we report an uncommon pediatric case of ALL with cryptic ins(22;9)(q11;q34q34) and p190-type BCR-ABL1 transcript. We performed interphase fluorescence in situ hybridization (FISH) for BCR-ABL1 rearrangement on blood neutrophils, which was positive consistent with the diagnosis of lymphoid blast crisis of CML...
April 25, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28444644/ponatinib-in-japanese-patients-with-philadelphia-chromosome-positive-leukemia-a-phase-1-2-study
#7
Arinobu Tojo, Taiichi Kyo, Kazuhito Yamamoto, Hirohisa Nakamae, Naoto Takahashi, Yukio Kobayashi, Tetsuzo Tauchi, Shinichiro Okamoto, Koichi Miyamura, Kiyohiko Hatake, Hiromi Iwasaki, Itaru Matsumura, Noriko Usui, Tomoki Naoe, Meera Tugnait, Narayana I Narasimhan, Stephanie Lustgarten, Heinrich Farin, Frank Haluska, Kazuma Ohyashiki
In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2)...
April 25, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28437552/bcr-abl1-transcript-types-showed-distinct-laboratory-characteristics-in-patients-with-chronic-myeloid-leukemia
#8
A P Vasconcelos, I F Azevedo, F C B C Melo, W B Neves, A C A C Azevedo, R A M Melo
In chronic myeloid leukemia (CML) two main types of messenger RNA (e14a2 and e13a2) can be produced by BCR-ABL1 gene rearrangement. Due to conflicting results, the clinical value of these transcripts remains controversial. The aim of this study was to identify associations of e14a2 and e13a2 transcripts with laboratory variables and also the response to treatment. This study included 203 adult patients with CML treated with Imatinib as first-line drug in a reference hematology center in Northeast Brazil. Clinical and laboratory data were obtained after informed consent...
April 20, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28435469/interleukin-3-receptor-targeted-exosomes-inhibit-in-vitro-and-in-vivo-chronic-myelogenous-leukemia-cell-growth
#9
Daniele Bellavia, Stefania Raimondo, Giovanna Calabrese, Stefano Forte, Marta Cristaldi, Agostina Patinella, Lorenzo Memeo, Mauro Manno, Samuele Raccosta, Patrizia Diana, Girolamo Cirrincione, Gianluca Giavaresi, Francesca Monteleone, Simona Fontana, Giacomo De Leo, Riccardo Alessandro
Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents...
2017: Theranostics
https://www.readbyqxmd.com/read/28433882/hypothyroidism-following-allogeneic-hematopoietic-stem-cell-transplantation-for-acute-myeloid-leukemia
#10
Michael Medinger, Deborah Zeiter, Dominik Heim, Jörg Halter, Sabine Gerull, André Tichelli, Jakob Passweg, Nicole Nigro
BACKGROUND: Hypothyroidism may complicate allogeneic hematopoietic stem cell transplantation (allo-HSCT); we therefore analyzed risk factors in this study. PATIENTS AND METHODS: We studied 229 patients with acute myeloid leukemia (AML) who underwent an allo-HSCT between 2003 and 2013 with different conditioning regimens (myeloablative, reduced-intensity, chemotherapy-based, or total body irradiation-based). Thyroid-stimulating hormone (TSH) and free thyroxine levels (fT4) were available in 104 patients before and after allo-HSCT...
April 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28433749/novel-sulphur-containing-imatinib-metabolites-found-by-untargeted-lc-hrms-analysis
#11
Ivo Vrobel, David Friedecký, Edgar Faber, Lukáš Najdekr, Kateřina Mičová, Radana Karlíková, Tomáš Adam
Untargeted metabolite profiling using high-resolution mass spectrometry coupled with liquid chromatography (LC-HRMS), followed by data analysis with the Compound Discoverer 2.0™ software, was used to study the metabolism of imatinib in humans with chronic myeloid leukemia. Plasma samples from control (drug-free) and patient (treated with imatinib) groups were analyzed in full-scan mode and the unknown ions occurring only in the patient group were then, as potential imatinib metabolites, subjected to multi-stage fragmentation in order to elucidate their structure...
April 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28431398/decreased-calpain-activity-in-chronic-myeloid-leukemia-impairs-apoptosis-by-increasing-survivin-in-myeloid-progenitors-and-xiap1-in-differentiating-granulocytes
#12
Weiqi Huang, Ling Bei, Elizabeth E Hjort, Elizabeth A Eklund
Chronic Myeloid Leukemia (CML) is characterized by translocations between chromosomes 9 and 22, resulting in expression of Bcr-abl oncogenes. Although the clinical course of CML was revolutionized by development of Bcr-abl-directed tyrosine kinase inhibitors (TKIs), CML is not cured by these agents. Specifically, the majority of subjects relapsed in clinical trials attempting TKI discontinuation, suggesting persistence of leukemia stem cells (LSCs) even in molecular remission. Identifying mechanisms of CML-LSC persistence may suggest rationale therapeutic targets to augment TKI efficacy and lead to cure...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423730/the-sclttaxbcr-abl-transgenic-mouse-model-closely-reflects-the-differential-effects-of-dasatinib-on-normal-and-malignant-hematopoiesis-in-chronic-phase-cml-patients
#13
Claudia Schubert, Nicolas Chatain, Till Braunschweig, Mirle Schemionek, Kristina Feldberg, Melanie Hoffmann, Olli Dufva, Satu Mustjoki, Tim H Brümmendorf, Steffen Koschmieder
The second generation tyrosine kinase inhibitor (TKI) dasatinib is a clinically approved drug for chronic myeloid leukemia (CML) as well as Ph+ acute lymphoblastic leukemia. In addition to its antileukemic effects, dasatinib was shown to impact on normal hematopoiesis and cells of the immune system.Due to the fact that the murine in vivo studies so far have not been performed in a chronic-phase CML model under steady-state conditions, our aim was to study the hematopoietic effects of dasatinib (20 mg/kg p.o...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423649/stellettin-b-induces-apoptosis-in-human-chronic-myeloid-leukemia-cells-via-targeting-pi3k-and-stat5
#14
Yali Chen, Qianxiang Zhou, Lei Zhang, Yuxu Zhong, Guanwei Fan, Zhe Zhang, Ran Wang, Meihua Jin, Yuling Qiu, Dexin Kong
Novel agents are still urgently expected for therapy of chronic myeloid leukemia (CML). The in vitro anti-leukemia activity of Stellettin B (Stel B), a triterpenoid we isolated from marine sponge Jaspis stellifera, on human CML K562 and KU812 cells was recently investigated. Stel B inhibited K562 and KU812 cell proliferation with IC50 as 0.035 μM and 0.95 μM respectively. While no obvious cell cycle arrest was observed, apoptosis was induced in K562 cells after Stel B treatment. The Stel B-induced apoptosis might be in mitochondrial pathway, with increase of Bad and Bax, decrease of Bcl-2 and activation of caspase-9...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420426/genotypes-of-slc22a4-and-slc22a5-regulatory-loci-are-predictive-of-the-response-of-chronic-myeloid-leukemia-patients-to-imatinib-treatment
#15
Monika Jaruskova, Nikola Curik, Rajna Hercog, Vaclava Polivkova, Eliska Motlova, Vladimir Benes, Hana Klamova, Pavla Pecherkova, Petra Belohlavkova, Filip Vrbacky, Katerina Machova Polakova
BACKGROUND: Through high-throughput next-generation sequencing of promoters of solute carrier and ATP-binding cassette genes, which encode drug transporters, we aimed to identify SNPs associated with the response to imatinib administered for first-line treatment of patients with chronic myeloid leukemia. METHODS: In silico analysis using publicly available databases was done to select the SLC and ABC genes and their promoters for the next-generation sequencing. SNPs associated with the imatinib response were identified using Fisher's exact probability tests and subjected to the linkage disequilibrium analyses with regulatory loci of concerned genes...
April 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28420292/neuroendocrine-tumor-of-cecum-in-patient-treated-with-imatinib-mesylate-for-blastic-phase-of-chronic-myeloid-leukemia
#16
Sabina Novaković, Anamarija Kovač Peić, Hrvoje Holik, Božena Coha
Imatinib mesylate (IM), a tyrosine kinase inhibitor, is the treatment of choice in patients with chronic myeloid leukemia (CML). It is considered a very safe drug, with mostly mild and reversible side effects. Lately, it has been suggested that adverse events may occur after a long term. We report a case of a 72-year-old woman diagnosed with blastic phase of Philadelphia chromosome positive CML treated with IM for 28 months. The patient presented first with ascites as a side effect of the drug. When the ascites re-occurred, it was caused by neuroendocrine tumor (NET) with peritoneal carcinomatosis...
April 19, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28418880/contributions-of-met-activation-to-bcr-abl1-tyrosine-kinase-inhibitor-resistance-in-chronic-myeloid-leukemia-cells
#17
Masanobu Tsubaki, Tomoya Takeda, Toshiki Kino, Kazuko Sakai, Tatsuki Itoh, Motohiro Imano, Takashi Nakayama, Kazuto Nishio, Takao Satou, Shozo Nishida
Resistance to the breakpoint cluster region-abelson 1 (BCR-ABL1) tyrosine kinase inhibitor (TKI) imatinib poses a major problem when treating chronic myeloid leukemia (CML). Imatinib resistance often results from a secondary mutation in BCR-ABL1. However, in the absence of a mutation in BCR-ABL1, the basis of BCR-ABL1-independent resistance must be elucidated. To gain insight into the mechanisms of BCR-ABL1-independent imatinib resistance, we performed an array-based comparative genomic hybridization. We identified various resistance-related genes, and focused on MET...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418852/structural-homologies-between-phenformin-lipitor-and-gleevec-aim-the-same-metabolic-oncotarget-in-leukemia-and-melanoma
#18
REVIEW
Gábor Somlyai, T Que Collins, Emmanuelle J Meuillet, Patel Hitendra, Dominic P D'Agostino, László G Boros
Phenformin's recently demonstrated efficacy in melanoma and Gleevec's demonstrated anti-proliferative action in chronic myeloid leukemia may lie within these drugs' significant pharmacokinetics, pharmacodynamics and structural homologies, which are reviewed herein. Gleevec's success in turning a fatal leukemia into a manageable chronic disease has been trumpeted in medical, economic, political and social circles because it is considered the first successful targeted therapy. Investments have been immense in omics analyses and while in some cases they greatly helped the management of patients, in others targeted therapies failed to achieve clinically stable recurrence-free disease course or to substantially extend survival...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416739/tki-rotation-induced-persistent-deep-molecular-response-in-multi-resistant-blast-crisis-of-ph-cml
#19
Peter Valent, Susanne Herndlhofer, Mathias Schneeweiß, Bernd Boidol, Anna Ringler, Stefan Kubicek, Karoline V Gleixner, Gregor Hoermann, Emir Hadzijusufovic, Leonhard Müllauer, Wolfgang R Sperr, Giulio Superti-Furga, Christine Mannhalter
In chronic myeloid leukemia (CML) resistance against one or more BCR-ABL1 tyrosine kinase inhibitors (TKI) remains a clinical challenge. Preclinical data suggest that TKI combinations may overcome resistance. We report on a heavily pre-treated 78 year-old female patient with CML who developed multi-resistant blast crisis with bone marrow fibrosis and a Ph- clone. Treatment with ponatinib resulted in blast cell clearance, decrease in fibrosis, and disappearance of BCR-ABL1, but also in severe thrombocytopenia with bleedings requiring platelet transfusions...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410239/homoharringtonine-suppresses-imatinib-resistance-via-the-bcl-6-p53-pathway-in-chronic-myeloid-leukemia-cell-lines
#20
Qian Wang, Wei Ding, Yihan Ding, Jingjing Ma, Zhaoye Qian, Jingxian Shao, Yufeng Li
BACKGROUND: The anti-leukemic mechanism of homoharringtonine (HHT) differs from that of IM, and HHT is one of the most useful agents for use in patients with IM resistance or intolerance. The Bcl-6/p53 pathway has been shown to regulate the sensitivity of tumor cells to antitumor drugs. We tested whether HHT blocked the Bcl-6/p53 pathway in order to promote the apoptosis of IM-resistant cells in vitro and in vivo. RESULTS: Ph+ acute lymphoblastic leukemia (ALL) cells and IM-resistant chronic myeloid leukemia (CML) cells showed high expression of Bcl-6 protein...
March 31, 2017: Oncotarget
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