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https://www.readbyqxmd.com/read/29691899/droplet-digital-pcr-for-bcr-abl-p210-detecting-of-cml-a-high-sensitive-method-of-the-minimal-residual-disease-disease-progression
#1
Wen-Jun Wang, Chao-Feng Zheng, Zhuang Liu, Yan-Hong Tan, Xiu-Hua Chen, Bin-Liang Zhao, Guo-Xia Li, Zhi-Fang Xu, Fang-Gang Ren, Yao-Fang Zhang, Jian-Mei Chang, Hong-Wei Wang
OBJECTIVE: The present study intended to establish a droplet digital PCR (dd-PCR) for monitoring minimal residual disease (MRD) in patients with BCR/ABL (P210)-positive CML, thereby achieving deep-level monitoring of tumor load and determining the efficacy for guided clinically individualized treatment. METHODS: Using dd-PCR and RT-qPCR, two cell suspensions were obtained from K562 cells and normal peripheral blood mononuclear cells by gradient dilution and were measured at the cellular level...
April 25, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29686565/chronic-neutrophilic-leukemia
#2
Arthur Bredeweg, Micah Burch, John R Krause
Chronic neutrophilic leukemia is a rare myeloproliferative disorder characterized by a sustained peripheral blood neutrophilia, absence of the BCR/ABL oncoprotein, bone marrow hypercellularity with less than 5% myeloblasts and normal neutrophil maturation, and no dysplasia. This leukemia has been associated with mutations in the colony-stimulating factor 3 receptor (CSF3R) that may activate this receptor, leading to the proliferation of neutrophils that are the hallmark of chronic neutrophilic leukemia. We present a case of chronic neutrophilic leukemia and discuss the criteria for diagnosis and the significance of mutations found in this leukemia...
January 2018: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/29675611/ponatinib-as-second-line-treatment-in-chronic-phase-chronic-myeloid-leukemia-patients-in-real-life-practice
#3
Massimo Breccia, Elisabetta Abruzzese, Fausto Castagnetti, Massimiliano Bonifacio, Domenica Gangemi, Federica Sorà, Alessandra Iurlo, Luigiana Luciano, Antonella Gozzini, Massimo Gentile, Monica Bocchia, Debora Luzi, Alessandro Maggi, Nicola Sgherza, Alessandro Isidori, Monica Crugnola, Patrizia Pregno, Anna Rita Scortechini, Isabella Capodanno, Michele Pizzuti, Robin Foà
Scarce information is available on the use of ponatinib as second-line treatment in chronic phase chronic myeloid leukemia (CP-CML) patients resistant and/or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. We collected data from 29 CML patients, with a median age of 54 years (range 32-72). Eleven patients had received dasatinib, 15 patients received nilotinib, and 3 patients received imatinib as first-line treatment. Forty-five percent of patients started ponatinib for secondary resistance, 38% for primary resistance, 7% for severe intolerance associated to a molecular warning, 7% due to the presence of a T315I mutation, and 3% for severe intolerance...
April 19, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29670043/wool-like-hollow-polymeric-nanoparticles-for-cml-chemo-combinatorial-therapy
#4
Barbara Cortese, Stefania D'Amone, Ilaria Elena Palamà
Chronic myeloid leukaemia (CML) is caused by the BCR-ABL oncogene, which encodes the constitutively active BCR-ABL tyrosine kinase. Targeted therapy with tyrosine-kinase inhibitors induces a partial cytogenetic response in most patients. Nanosystems can represent an opportunity for combinatorial therapy with the capacity to simultaneously release different therapeutic agents, checking the pharmacokinetic properties. In this work, we have developed a novel poly-(ε-caprolactone) (PCL) nanosystem for combinatorial therapy in CML, composed of a biodegradable pH sensitive core releasing Nilotinib (Nil) and an enzymatic sensitive outer shell releasing Imatinib Mesylate (IM), resulting in wool-like nanoparticles (NPs)...
April 18, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29669505/aberrant-dna-methylation-of-socs1-gene-is-not-associated-with-resistance-to-imatinib-mesylate-among-chronic-myeloid-leukemia-patients
#5
Marjanu Hikmah Elias, Husin Azlan, Abdul Aziz Baba, Ravindran Ankathil
BACKGROUND: In exploring the cause of Imatinib mesylate (IM) resistance among chronic myeloid leukemia (CML) patients who do not harbouring BCR-ABL dependent mechanism, BCR-ABL independent pathways are the most possible pathways that should be explored. In BCR-ABL independent pathway, SOCS1 plays an important role as it helps to regulate optimal JAK/STAT activity. OBJECTIVE: To identify the association of SOCS1 gene hypermethylation in mediating IM Resistance. METHOD: The SOCS1 promoter methylation level of 92 BCR-ABL non mutated IM resistant CML patients, 83 IM good response CML patients and 5 normal samples from healthy individuals were measured using Methylation Specific- High Resolution Melt (MS-HRM) analysis...
April 18, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29665937/-current-understanding-of-myeloproliferative-neoplasm-related-gene-mutations-and-cytokine-review
#6
Zhi-Peng He, Yong Wu
Myeloproliferative neoplasm(MPN) is clonal hematopoietic stem cell disorder characterized by abnormal proliferation and expansion of one or more myeloid lineages. BCR-ABL-negative MPN includes polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The mutations of JAK2, CALR and MPL genes are involved in the pathogenesis of MPN that provided a more complete molecular diagnostic standard for MPN. More and more new mutated genes related to prognosis of MPN were discovered in the past few years, at same time it was found that cytokines were also involved in the genesis and development of MPN...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665896/-a-modified-protocol-for-rapid-establishing-mouse-model-with-ph-positive-acute-lymphoblastic-leukemia
#7
Na Qi, Xue Wang, Qing-Yun Wu, Zhi-Ling Yan, Lin Wang, Chong Chen, Kai-Lin Xu
OBJECTIVE: To investigate a modified protocol of establishing mouse Ph+ ALL model so as to provide a more convenient and more powerful tool for Ph+ ALL studies. METHODS: Immature B cells from BALB/c mice were transfected with the Mig190 retrovirus and infused into irradiated syngeneic mice. The immunophenotype was identified by flow cytometry, the BCR-ABL was identified by RT-PCR and Western blot. Leukemia cells isolated from sick mice were re-infused into syngeneic mice without irradiation...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665256/bcr-abl-enhances-the-prolyl-isomerase-activity-of-pin-1-by-interacting-with-dapk1-in-ph-all
#8
Wen-Bin Cao, Jian-Feng Yao, Si-Zhou Feng, Yi He, Er-Lie Jiang, Rong-Li Zhang, Dong-Lin Yang, Ming Gong, Xiao-Hui Zheng, Shu-Lian Chen, Jia-Li Sun, Lu-Kun Zhou, Ming-Zhe Han
Philadelphia chromosome (Ph)/BCR-ABL-positive (ph+ ) ALL is the most common genetic abnormality associated with ALL and has been shown to confer the worst prognosis to both children and adults. Increasing evidence has revealed that the dysregulation of prolyl isomerase Pin 1 contributes to multicancer development and progression, including ALL, although the underlying molecular mechanisms remain unclear. Here, we report that the expression of Pin 1 was enhanced in ph+ ALL patient samples and was associated positively with the expression of BCR-ABL...
April 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29663362/cd69-partially-inhibits-apoptosis-and-erythroid-differentiation-via-cd24-and-their-knockdown-increase-imatinib-sensitivity-in-bcr-abl-positive-cells
#9
Shih-Yun Huang, Yu-Hsiu Liu, Yi-Ju Chen, Yi-Yen Yeh, Huei-Mei Huang
Chronic myeloid leukemia (CML) is caused by a constitutively active BCR-ABL tyrosine kinase. Tyrosine kinase inhibitors (TKIs) imatinib and its derivatives represent a breakthrough for CML therapy, but the use of TKI alone is ineffective for many CML patients. CD69, an early activation marker of lymphocytes, participates in immune and inflammatory responses. Previous studies revealed that BCR-ABL upregulates CD69 expression; however, the role of CD69 in CML cells is unknown. Here, we demonstrate that BCR-ABL induced CD69 promoter activity and mRNA and protein expression via the NF-κB pathway...
April 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29660671/computational-study-of-molecular-electrostatic-potential-docking-and-dynamics-simulations-of-gallic-acid-derivatives-as-abl-inhibitors
#10
K R Raghi, D R Sherin, M J Saumya, P S Arun, V N Sobha, T K Manojkumar
Chronic myeloid leukemia (CML), a hematological malignancy arises due to the spontaneous fusion of the BCR and ABL gene, resulting in a constitutively active tyrosine kinase (BCR-ABL). Pharmacological activity of Gallic acid and 1,3,4-Oxadiazole as potential inhibitors of ABL kinase has already been reported. Objective of this study is to evaluate the ABL kinase inhibitory activity of derivatives of Gallic acid fused with 1,3,4-Oxadiazole moieties. Attempts have been made to identify the key structural features responsible for drug likeness of the Gallic acid and the 1,3,4-Oxadiazole ring using molecular electrostatic potential maps (MESP)...
April 5, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29648816/the-pharmacophore-network-a-computational-method-for-exploring-structure-activity-relationships-from-a-large-chemical-dataset
#11
Jean-Philippe Métivier, Bertrand Cuissart, Ronan Bureau, Alban Lepailleur
Historically, structure-activity relationships (SAR) analysis has focused on small sets of molecules but in recent years, there has been increasing efforts to analyze the growing amount of data stored in public databases like ChEMBL. The pharmacophore network introduced herein is dedicated to the organization of a set of pharmacophores automatically discovered from a large dataset of molecules. The network navigation allows to derive essential tasks of a drug discovery process, including the study of the relations between different chemical series, the analysis of the influence of additional chemical features on the compounds' activity, and the identification of diverse binding modes...
April 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29625382/phthalimide-conjugations-for-the-degradation-of-oncogenic-pi3k
#12
Wenlu Li, Chunmei Gao, Lei Zhao, Zigao Yuan, Yuzong Chen, Yuyang Jiang
PI3K/Akt/mTOR pathway is crucial for carcinogenesis and its inhibitors have made a great progress in cancer treatment. However, there is still a great developing space for PI3K inhibitors as the acquired drug resistance hindered their application in clinical. Proteolysis-targeting chimeras (PROTACs) with the potential to handle the challenges faced in drug development could be an alternative therapeutic strategy. Moreover, the past two years have witnessed remarkable advances in the development of phthalimide conjugation as a strategy for the degradation instead of inhibition of the targets, including BET family proteins, Sirtuin 2, CDK 9, Smad 3, and BCR-ABL proteins...
March 26, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29622863/summary-and-review-of-the-abstracts-on-philadelphia-negative-myeloproliferative-neoplasms-presented-at-haematocon-2017
#13
Tathagata Chatterjee, Ankur Ahuja
There are lot of grey zones in Philadelphia negative chronic myeloproliferative neoplasms (CMPNs) and that's the reason they are in hit list of researchers. Having a spectrum of disorders their diagnosis is very important and especially to differentiate from each other since they overlap with each other in many ways. Diagnosis doesn't start from lab but with clinical phenotype. Clinical phenotype not only able to provide us the diagnosis but also helps in management of the disease per se. When diagnosis comes, the old timer but an evergreen morphology plays an important role which along with the newer generation tool "molecular" helps in differentiating these disorders...
April 2018: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29620650/durable-remission-in-a-patient-of-mixed-phenotype-acute-leukemia-with-philadelphia-chromosome-positive-treated-with-nilotinib-and-lenalidomide-a-case-report
#14
Binbin Lai, Qitian Mu, Huiling Zhu, Yi Wang, Yi Zhang, Kaihong Xu, Lixia Sheng, Guifang Ouyang
RATIONALE: Philadelphia chromosome-positive mixed phenotype acute leukemia (Ph+ MPAL) is a rare type of leukemia with poor prognosis. Tyrosine kinase inhibitors (TKIs) in combination with chemotherapy have significantly improved its remission rate. However, relapse remains the major obstacle to achieve long survival. Lenalidomide is a second-generation oral immunomodulatory drug that has been broadly applied in the treatment of various hematological malignancies. PATIENT CONCERNS: A 54-year-old Chinese male patient who complained of chest pain and fatigue for 20 days...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29620139/antiproliferative-effects-of-imatinib-mesylate-on-zr%C3%A2-75%C3%A2-1-and-mda%C3%A2-mb%C3%A2-231-cell-lines-via-pdgfr%C3%A2-%C3%AE-pdgf%C3%A2-bb-c%C3%A2-kit-and-scf-expression
#15
Ali Kadivar, Mohamed Ibrahim Noordin, Arya Aditya, Behnam Kamalidehghan, Ehsan Taghizadeh Davoudi, Reihaneh Sedghi, Hamid Akbari Javar
Imatinib mesylate is an anti‑neoplastic targeted chemotherapeutic agent, which can inhibit tyrosine kinase receptors, including BCR‑ABL, platelet‑derived growth factor receptors (PDGFRs) and c‑Kit. Cellular processes, including differentiation, proliferation and survival are regulated by these receptors. The present study aimed to evaluate the antiproliferative effects of imatinib mesylate, and its effects on apoptotic induction and cell cycle arrest in breast cancer cell lines. In addition, the study aimed to determine whether the effects of this drug were associated with the mRNA and protein expression levels of PDGFR‑β, c‑Kit, and their corresponding ligands PDGF‑BB and stem cell factor (SCF), which may potentially modulate cell survival and proliferation...
March 27, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29614307/lc-ms-ms-reveals-the-formation-of-reactive-ortho-quinone-and-iminium-intermediates-in-saracatinib-metabolism-phase-i-metabolic-profiling
#16
Mohamed W Attwa, Adnan A Kadi, Hany W Darwish, Haitham Alrabiah
Saracatinib (AZD-0530) is a drug under clinical trials that developed by AstraZeneca. It is considered a dual kinase inhibitor, with selective actions as a Src inhibitor and a Bcr-Abl tyrosine-kinase inhibitor. Saracatinib chemical structure contains N-methyl piperazine group and 1,3 benzodioxole group. N-methyl piperazine group that can be bioactivated to form iminium intermediates which can be captured by KCN. 1,3-Benzodioxole group can be bioactivated to form ortho-quinone intermediate that can be conjugated with GSH...
March 31, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29609532/design-and-rationale-for-the-life-after-stopping-tyrosine-kinase-inhibitors-last-study-a-prospective-single-group-longitudinal-study-in-patients-with-chronic-myeloid-leukemia
#17
Ehab Atallah, Charles A Schiffer, Kevin P Weinfurt, Mei-Jie Zhang, Jerald P Radich, Vivian G Oehler, Javier Pinilla-Ibarz, Michael W N Deininger, Li Lin, Richard A Larson, Michael J Mauro, Joseph O Moore, Ellen K Ritchie, Neil P Shah, Richard T Silver, Martha Wadleigh, Jorge Cortes, James Thompson, Jessica Guhl, Mary M Horowitz, Kathryn E Flynn
BACKGROUND: Treatment of chronic myeloid leukemia with a tyrosine kinase inhibitor (TKI) offers significant improvements over previous treatments in terms of survival and toxicity yet nevertheless is associated with reduced health-related quality of life and very high cost. Several small studies from Europe and Australia suggested that discontinuing TKIs with regular monitoring was safe. METHODS: The Life After Stopping TKIs (LAST) study is a large, U.S.-based study that aims to improve the evidence for clinical decision making regarding TKI discontinuation with monitoring in patients with chronic myeloid leukemia who have a deep molecular response to TKI therapy...
April 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29601636/mean-residual-life-regression-with-functional-principal-component-analysis-on-longitudinal-data-for-dynamic-prediction
#18
Xiao Lin, Tao Lu, Fangrong Yan, Ruosha Li, Xuelin Huang
Predicting patient life expectancy is of great importance for clinicians in making treatment decisions. This prediction needs to be conducted in a dynamic manner, based on longitudinal biomarkers repeatedly measured during the patient's post-treatment follow-up period. The prediction is updated any time a new biomarker measurement is obtained. The heterogeneity across patients of biomarker trajectories over time requires flexible and powerful approaches to model noisy and irregularly measured longitudinal data...
March 30, 2018: Biometrics
https://www.readbyqxmd.com/read/29578162/the-autophagy-induced-by-curcumin-via-mek-erk-pathway-plays-an-early-anti-leukemia-role-in-human-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-sup-b15-cells
#19
Yong Guo, Qing Qing Shan, Ping Yu Gong, Sen Chun Wang
Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by BCR/ABL tyrosine kinase which activates the downstream signaling pathways, such as Akt/mTOR, RAF/MEK/ERK, and STAT5 pathways. Curcumin has been shown to have inhibitory effects on cancers by inducing apoptosis and autophagy. We demonstrated that curcumin inhibited activation of Akt-mTOR, ABL/STAT5 pathways, inhibited cell proliferation, and induced apoptosis in Ph+ ALL cells. Experiments here, were conducted to determine whether autophagy via MEK/ERK pathway involved in anti-leukemia effect of curcumin in Ph+ ALL...
2018: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29572111/comparative-analysis-of-flow-cytometry-and-rq-pcr-for-the-detection-of-minimal-residual-disease-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-after-hematopoietic-stem-cell-transplantation
#20
Xiangyu Zhao, Xiaosu Zhao, Huan Chen, Yazhen Qin, Lanping Xu, Xiaohui Zhang, Kaiyan Liu, Xiaojun Huang, Yingjun Chang
The aim of this study was to examine the value of MRD detection by multiparameter flow cytometry (MFC) and RQ-PCR at the early stage after hematopoietic stem cell transplantation (HSCT) for predicting relapse and leukemia-free survival (LFS) in Philadelphia chromosome-positive ALL (Ph+-ALL). Patients who maintained complete molecular remission (CMR, BCR/ABL<0.01%) status at 1 and 3 months were associated with a lower relapse rate (P=0.02 and <0.001) and better LFS (P=0.014 and 0.013) than those without a CMR...
March 20, 2018: Biology of Blood and Marrow Transplantation
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