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https://www.readbyqxmd.com/read/28822797/influence-of-bcr-abl-transcript-type-on-outcome-in-patients-with-chronic-phase-chronic-myeloid-leukemia-treated-with%C3%A2-imatinib
#1
Katia Borgia Barbosa Pagnano, Eliana Cristina Miranda, Márcia Torresan Delamain, Gislaine Oliveira Duarte, Erich Vinicius de Paula, Irene Lorand-Metze, Carmino Antonio de Souza
BACKGROUND: The prognostic significance of breakpoint cluster region gene-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) transcripts in chronic myeloid leukemia (CML) is still controversial. PATIENTS AND METHODS: All consecutive CML patients in chronic phase treated with imatinib in a single center were analyzed (n = 170). BCR-ABL1 transcript was evaluated using multiplex reverse transcription polymerase chain reaction. Exclusively patients with BCR-ABL transcripts e13a2 and/or e14a2 were included in this analysis...
June 21, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28819731/erratum-to-a-novel-tubulin-polymerization-inhibitor-mpt0b206-downregulates-bcr-abl-expression-and-induces-apoptosis-in-imatinib-sensitive-and-imatinib-resistant-cml-cells
#2
Chih-Wei Chen, Yueh-Lun Lee, Jing-Ping Liou, Yu-Hsiu Liu, Chin-Wei Liu, Tsai-Yun Chen, Huei-Mei Huan
No abstract text is available yet for this article.
August 18, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28819285/phosphorylation-of-sos1-on-tyrosine-1196-promotes-its-rac-gef-activity-and-contributes-to-bcr-abl-leukemogenesis
#3
S Gerboth, E Frittoli, A Palamidessi, F C Baltanas, S Mogjiborahman, J Rappsilber, C Giuliani, F Troglio, Y Rolland, G Pruneri, S Kreutmair, I Pallavicini, M Zobel, M Cinquanta, S Minucci, C Gomez, E Santos, A L Illert, G Scita
Son of Sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the small GTPases RAC and RAS. While the molecular mechanisms of RAS GEF catalysis have been unveiled, how SOS1 acquires RAC GEF activity and what is the physio-pathological relevance of this activity is much less understood. Here, we show that SOS1 is tyrosine phosphorylated on Y1196 by ABL. Phosphorylation of Y1196 controls SOS1 inter-molecular interaction, is required to promote the exchange of nucleotides on RAC in vitro, and for PDGF activation of RAC and RAC-dependent actin remodeling and cell migration...
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28810255/ponatinib-induced-graft-versus-host-disease-graft-versus-leukemia-effect-in-a-patient-with-philadelphia-positive-acute-lymphoblastic-leukemia-without-the-t315i-mutation-relapsing-after-allogeneic-transplant
#4
Annamaria Petrungaro, Massimo Gentile, Carla Mazzone, Rosa Greco, Giuseppina Uccello, Anna Grazia Recchia, Laura De Stefano, Sabrina Bossio, Angela Palummo, Rosellina Morelli, Caterina Musolino, Fortunato Morabito, Ernesto Vigna
We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i...
August 16, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28801986/persistent-detection-of-alternatively-spliced-bcr-abl-variant-results-in-a-failure-to-achieve-deep-molecular-response
#5
Junichiro Yuda, Toshihiro Miyamoto, Jun Odawara, Yasuyuki Ohkawa, Yuichiro Semba, Masayasu Hayashi, Koichi Miyamura, Mitsune Tanimoto, Kazuhito Yamamoto, Masafumi Taniwaki, Koichi Akashi
Treatment with tyrosine kinase inhibitors (TKIs) may sequentially induce TKI-resistant BCR-ABL mutants in chronic myeloid leukemia (CML). Conventional polymerase chain reaction (PCR) monitoring of BCR-ABL is an important indicator to determine therapeutic intervention for preventing disease progression. However, PCR cannot quantify separately amounts of BCR-ABL and its mutants, including alternatively spliced BCR-ABL with an insertion of 35 intronic nucleotides (BCR-ABL(I)(ns35bp) ) between ABL exons 8 and 9 which introduces the premature termination and loss of kinase activity...
August 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28801299/-effect-of-bortezomib-in-inducing-apoptosis-of-imatinib-resistant-k562-cells-and-the-mechanism
#6
Jia-Ye Hua, Xu-Hong Zhou, Shu-Ting Ouyang, Yong-Bin Wu
OBJECTIVE: To investigate the effect of bortezomib in inducing apoptosis in imatinib-resistant K562 (K562R) cells and its possible mechanism. METHODS: K562 cells were cultured in gradient concentrations of imatinib for several months to generate imatinib-resistant K562 cells. The viability of K562R cells treated with bortezomib was measured using CCK-8 cell proliferation assay, and the cell apoptosis was analyzed by flow cytometry with annexin V/PI dual staining...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28781850/t315i-clone-selection-in-a-ph-all-patient-under-low-dose-ponatinib-maintenance
#7
Jasmine Noetzli, Mathilde Gavillet, Stavroula Masouridi-Levrat, Michel Duchosal, Olivier Spertini
We report here the clinical course of a Ph+ ALL patient who was treated with ponatinib 15 mg/day, as maintenance therapy, and developed a BCR-ABL T315I mutation leading to ALL relapse. This clonal evolution was reversed, without adverse effects, by increasing ponatinib to 45 mg/day. To our knowledge, we have been confronted with the first clinical case of a T315I clonal selection of ALL caused by subeffective therapeutic level of the drug. This single patient experience highlights the risk of T315I clone selection in Ph+ ALL treated with reduced dose ponatinib...
August 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28776669/hypomethylation-mediated-h19-overexpression-increases-the-risk-of-disease-evolution-through-the-association-with-bcr-abl-transcript-in-chronic-myeloid-leukemia
#8
Jing-Dong Zhou, Jiang Lin, Ting-Juan Zhang, Ji-Chun Ma, Xi-Xi Li, Xiang-Mei Wen, Hong Guo, Zi-Jun Xu, Zhao-Qun Deng, Wei Zhang, Jun Qian
Previous study has revealed that H19 expression is required for efficient tumor growth induced by BCR-ABL in chronic myeloid leukemia (CML). Herein, we further determined H19 expression and its clinical implication in patients with CML. H19 expression and methylation were detected by real-time quantitative PCR and real-time quantitative methylation-specific PCR, and then clinical implication of H19 expression was further analyzed. H19 expression was significantly up-regulated in CML patients (P < 0.001)...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28767619/women-administered-standard-dose-imatinib-for-chronic-myeloid-leukemia-have-higher-dose-adjusted-plasma-imatinib-and-norimatinib-concentrations-than-men
#9
Sarah L Belsey, Robin Ireland, Kathryn Lang, Aytug Kizilors, Aloysius Ho, Ghulam J Mufti, Alessandra Bisquera, Hugues De Lavallade, Robert J Flanagan
BACKGROUND: The standard dose of imatinib for the treatment of chronic-phase chronic myeloid leukemia (CML) is 400 mg d. A pre-dose plasma imatinib concentration of >1 mg L is associated with improved clinical response. This study aimed to assess the plasma imatinib and norimatinib concentrations attained in patients with CML administered standard doses of imatinib adjusted for dose, age, sex, body weight, and response. METHODS: We evaluated data from a cohort of patients treated between 2008-2014 with respect to dose, age, sex, body weight, and response...
July 31, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28760296/analysis-of-survival-of-patients-with-chronic-myeloid-leukemia-treated-with-imatinib-in-the-last-15-years-in-lebanon
#10
Marcel Massoud, Riwa Sakr, Fouad Kerbage, Joseph Makdissi, Jenny Hawi, Layale Rached, Fady Nasr, Georges Chahine
BACKGROUND: In the 2000s, the introduction of the tyrosine kinase inhibitor (TKI), imatinib, improved the survival outcomes of patients with chronic myeloid leukemia (CML). In Lebanon, we rapidly adopted this treatment strategy. To the best of our knowledge, this is the first study reporting the survival rates of Lebanese CML patients. We examined the rates of major molecular response (MMR) and complete cytogenetic response (CCyR) and analyzed the overall survival, progression-free survival, and event-free survival of CML patients treated with front-line imatinib in 3 university hospitals in Lebanon...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28757066/design-synthesis-and-biological-evaluation-of-lenalidomide-derivatives-as-tumor-angiogenesis-inhibitor
#11
Shengquan Hu, Libin Yuan, Hong Yan, Zhigang Li
Lenalidomide is a type of immunomodulatory agent with anti-tumor activity by mainly expressed in the anti-angiogenesis. In order to enhance the pharmacological activity of Lenalidomide, a series of Lenalidomide derivatives were designed as tumor angiogenesis inhibitors. The potential anti-angiogenesis targets of Lenalidomide derivatives were virtual screened on Auto-Dock 4.0 by using reverse docking method. The six target proteins, such as vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, BCR-ABL tyrosine kinase, p38 mitogen activated protein kinase and metal protein kinase, were chosen as the targets...
July 19, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28753604/socs1-function-in-bcr-abl-mediated-myeloproliferative-disease-is-dependent-on-the-cytokine-environment
#12
Özlem Demirel, Olivier Balló, Pavankumar N G Reddy, Olesya Vakhrusheva, Jing Zhang, Astrid Eichler, Ramona Fernandes, Susanne Badura, Hubert Serve, Christian Brandts
Treatment with tyrosine kinase inhibitors is the standard of care for Philadelphia chromosome positive leukemias. However the eradication of leukemia initiating cells remains a challenge. Circumstantial evidence suggests that the cytokine microenvironment may play a role in BCR-ABL mediated leukemogenesis and in imatinib resistance. Gene expression analyses of BCR-ABL positive ALL long-term cultured cells revealed strong reduction of SOCS mRNA expression after imatinib treatment, thereby demonstrating a strong inhibition of cytokine signaling...
2017: PloS One
https://www.readbyqxmd.com/read/28752075/mir-155-effectively-induces-apoptosis-in-k562-philadelphia-positive-cell-line-through-upregulation-of-p27kip1
#13
Mahdi Edalati Fathabad, Morteza Karimipoor, Shaban Alizadeh, Asghar Abdoli, Amir Atashi, Mahtab Sayadi
Introduction: Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by the Philadelphia chromosome translocation, at (9; 22), which results in BCR-ABL fusion tyrosine kinase oncoprotein. This fusion induces down-regulation of miR-155. Upregulation of miR-155 can influence cell fate via the effect on p27kip1 and apoptosis. The aim of this study was to induce apoptosis in K562 CML cell line by overexpression of miR-155. Methods: The K562 cell line was transfected with pLenti-III-pre mir155-GFP constructs through electroporation...
2017: BioImpacts: BI
https://www.readbyqxmd.com/read/28751559/loss-of-function-but-not-dominant-negative-intragenic-ikzf1-deletions-are-associated-with-an-adverse-prognosis-in-adult-bcr-abl-negative-acute-lymphoblastic-leukemia
#14
Benjamin Kobitzsch, Nicola Gökbuget, Stefan Schwartz, Richard Reinhardt, Monika Brüggemann, Andreas Viardot, Ralph Wäsch, Michael Starck, Eckhard Thiel, Dieter Hoelzer, Thomas Burmeister
Genetic alterations of the transcription factor IKZF1 ("IKAROS") are detected in around 15-30% of cases of BCR-ABL-negative B-cell precursor acute lymphoblastic leukemia (ALL). Different types of intragenic deletions have been observed, resulting in a functionally inactivated allele ("loss-of-function") or in "dominant-negative" isoforms. The prognostic impact of these alterations especially in adult acute lymphoblastic leukemia is not well defined. We analyzed 482 well-characterized cases of adult BCR-ABL-negative B-precursor acute lymphoblastic leukemia uniformly treated in the framework of the GMALL studies and detected IKZF1 alterations in 128 cases (27%)...
July 27, 2017: Haematologica
https://www.readbyqxmd.com/read/28751509/giant-oesophageal-gastrointestinal-stromal-tumour-presenting-with-dyspnoea-and-clubbed-fingers
#15
Yurie Yamamoto, Yosuke Sasaki, Michio Kougame, Naobumi Tochigi
Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms of the gastrointestinal tract originating from the interstitial cells of Cajal. Giant oesophageal GISTs are rare since the oesophagus is rarely the primary site of GISTs, and they are usually diagnosed early due to complaints such as dysphagia. We present the case of a giant oesophageal GIST presenting with prominent clubbing. The case underlined the diagnostic importance of clubbing and the careful consideration of chemotherapy. Although clubbed fingers associated with GISTs are rare, our experience demonstrates the importance of physicians' recognition of clubbing as a paraneoplastic phenomenon for early diagnosis of malignancies since patients seldom notice their own clubbing by themselves...
July 26, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28743118/disappearance-of-bone-marrow-fibrosis-in-a-patient-with-chronic-myeloid-leukemia-treated-with-dasatinib
#16
Ernesto Vigna, Bruno Martino, Francesco Bacci, Anna Grazia Recchia, Francesco Mendicino, Rosellina Morelli, Francesca Romana Mauro, Caterina Musolino, Rosa Greco, Eugenio Lucia, Elena Sabattini, Fortunato Morabito, Massimo Gentile
We report a case of a chronic myeloid leukemia patient showing progressive bone marrow fibrosis and anemia during imatinib therapy. Given the loss of major molecular response, we switched treatment to dasatinib 100 mg daily, observing a reduction in BCR-ABL transcript, a significant improvement of anemia, and a gradual disappearance of fibrosis. After 7 years of dasatinib therapy the patient maintains a complete cytogenetic response and a deep molecular response; the last bone biopsy confirmed the absence of fibrosis...
July 26, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28730479/analysis-of-drug-resistance-using-kinome-wide-functional-screens
#17
Katherine R Singleton, Keith T Earley, Lynn E Heasley
The clinical success of tyrosine kinase inhibitors specific for BCR-ABL-, EGFR-, ALK-, and ROS1-driven cancers continues to spur the quest to match specific oncogene-defined tumor types with an appropriate molecularly targeted therapy. Unfortunately, responses to these agents are not durable with intrinsic or acquired resistance limiting benefit. Additionally, efforts to identify the appropriate targets of new drugs have focused on nonfunctional assays such as large-scale sequencing for somatic mutations or analysis of gene copy number...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730166/impact-of-chromosomal-rearrangement-upon-dna-methylation-patterns-in-leukemia
#18
Hyang-Min Byun, Shahrooz Eshaghian, Dan Douer, Jonathen Trent, Guillermo Garcia-Manero, Ravi Bhatia, Kim Siegmund, Allen S Yang
Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the BCR-ABL translocation t(9:22), in establishing DNA methylation profiles in cancer. Materials and methods We compared DNA methylation of 1,505 selected promoter CpGs in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34+ hematopoietic stem cells transfected with BCR-ABL, and other tumors without BCR-ABL (acute promyelocytic leukemia (APL) and gastrointestinal stromal tumors (GIST)...
2017: Open Medicine (Warsaw, Poland)
https://www.readbyqxmd.com/read/28726645/chronic-myeloid-leukemia-expected-relapse-s-clinical-laboratory-indexes
#19
T Kirtava, D Ghirdaladze, T Vatsadze
Today Chronic Myeloid Leukemia (CML) relapse's final assessment and monitoring in the whole world is implemented by BCR-ABL gene quantitative detection - during the polymerase chain reaction (by PSR means). Implementation of this monitoring materially and technically is not often available and remission during years is being assessed using monthly clinical-laboratory data. Proceeding from this, the goal of our work was to find the clinical-laboratory features, indicating the expected relapse and require the urgent molecular research carry out...
June 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28719608/cholesterol-esterification-inhibition-and-imatinib-treatment-synergistically-inhibit-growth-of-bcr-abl-mutation-independent-resistant-chronic-myelogenous-leukemia
#20
Shovik Bandyopadhyay, Junjie Li, Elie Traer, Jeffrey W Tyner, Amy Zhou, Stephen T Oh, Ji-Xin Cheng
Since the advent of tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, and dasatinib, chronic myelogenous leukemia (CML) prognosis has improved greatly. However, ~30-40% of patients develop resistance to imatinib therapy. Although most resistance is caused by mutations in the BCR-ABL kinase domain, 50-85% of these patients develop resistance in the absence of new mutations. In these cases, targeting other pathways may be needed to regain clinical response. Using label-free Raman spectromicroscopy, we evaluated a number of leukemia cell lines and discovered an aberrant accumulation of cholesteryl ester (CE) in CML, which was found to be a result of BCR-ABL kinase activity...
2017: PloS One
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