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https://www.readbyqxmd.com/read/28224300/nilotinib-first-line-therapy-in-patients-with-philadelphia-chromosome-negative-bcr-abl-positive-chronic-myeloid-leukemia-in-chronic-phase-enest1st-sub-analysis
#1
Andreas Hochhaus, Franҫois-Xavier Mahon, Philipp le Coutre, Ljubomir Petrov, Jeroen J W M Janssen, Nicholas C P Cross, Delphine Rea, Fausto Castagnetti, Andrzej Hellmann, Gianantonio Rosti, Norbert Gattermann, Maria Liz Paciello Coronel, Maria Asuncion Echeveste Gutierrez, Valentin Garcia-Gutierrez, Beatrice Vincenzi, Luca Dezzani, Francis J Giles
PURPOSE: The ENEST1st sub-analysis presents data based on Philadelphia chromosome (Ph) status, i.e., Ph+ and Ph-/BCR-ABL1 + chronic myeloid leukemia. METHODS: Patients received nilotinib 300 mg twice daily, up to 24 months. RESULTS: At screening, 983 patients were identified as Ph+ and 30 patients as Ph-/BCR-ABL + based on cytogenetic and RT-PCR assessment; 76 patients had unknown karyotype (excluded from this sub-analysis). In the Ph-/BCR-ABL1 + subgroup, no additional chromosomal aberrations were reported...
February 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28218227/p190-bcr-abl-chronic-myeloid-leukemia-following-a-course-of-s-1-plus-oxaliplatin-therapy-for-advanced-gastric-adenocarcinoma
#2
Hua Wang, Zhi-Yong Wang, Chun-Hong Xin, Ying-Hui Shang, Rui Jing, Fa-Hong Yan, Si-Zhou Feng
No abstract text is available yet for this article.
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28214896/the-genomic-landscape-of-pax5-ikzf1-and-cdkn2a-b-alterations-in-b-cell-precursor-acute-lymphoblastic-leukemia
#3
Zhishuo Ou, Maureen Sherer, Jane Casey, Heather A Bakos, Kathleen Vitullo, Jie Hu, Erika Friehling, Susanne M Gollin, Urvashi Surti, Svetlana A Yatsenko
We present a comprehensive comparison of PAX5,IKZF1, and CDKN2A/B abnormalities in 21 B-cell precursor acute lymphoblastic leukemia (B-ALL) patients studied by aCGH and gene-specific FISH assays. In our cohort of B-ALL patients, alterations of IKZF1, PAX5, and CDKN2A/B were detected by aCGH analysis in 43, 52, and 57% of samples, respectively. Deletions of IKZF1 were present in 9 samples, including 5 cases positive for both PAX5 and IKZF1 deletions, implying digenic impairment. Furthermore, all cases with IKZF1 deletions also had additional genomic alterations, including BCR-ABL1 gene fusions, PAX5 deletions, CDKN2A/B deletions, and FLT3 amplification...
February 18, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28212528/the-crispr-cas9%C3%A2-system-efficiently-reverts-the-tumorigenic-ability-of-bcr-abl-in-vitro-and-in-a-xenograft-model-of-chronic-myeloid-leukemia
#4
Ignacio García-Tuñón, María Hernández-Sánchez, José Luis Ordoñez, Veronica Alonso-Pérez, Miguel Álamo-Quijada, Rocio Benito, Carmen Guerrero, Jesús María Hernández-Rivas, Manuel Sánchez-Martín
CRISPR/Cas9 technology was used to abrogate p210 oncoprotein expression in the Boff-p210 cell line, a pro-B line derived from interlukin-3-dependent Baf/3, that shows IL-3-independence arising from the constitutive expression of BCR-ABL p210. Using this approach, pools of Boff-p210-edited cells and single edited cell-derived clones were obtained and functionally studied in vitro. The loss of p210 expression in Boff-p210 cells resulted in the loss of ability to grow in the absence of IL-3, as the Baf/3 parental line, showing significantly increased apoptosis levels...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28210003/differential-signaling-through-p190-and-p210-bcr-abl-fusion-proteins-revealed-by-interactome-and-phosphoproteome-analysis
#5
J A Cutler, R Tahir, S K Sreenivasamurthy, C Mitchell, S Renuse, R S Nirujogi, A H Patil, M Heydarian, X Wong, X Wu, T-C Huang, M-S Kim, K Reddy, A Pandey
Two major types of leukemogenic BCR-ABL fusion proteins are p190(BCR-ABL) and p210(BCR-ABL). Although the two fusion proteins are closely related, they can lead to different clinical outcomes. A thorough understanding of the signaling programs employed by these two fusion proteins is necessary to explain these clinical differences. We took an integrated approach by coupling protein-protein interaction analysis using biotinylation identification (BioID) with global phosphorylation analysis to investigate the differences in signaling between these two fusion proteins...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28196667/stress-granules-assembly-affects-detection-of-mrna-in-living-cells-by-the-nanoflares-an-important-aspect-of-the-technology
#6
Magdalena Wolczyk, Paulina Podszywalow-Bartnicka, Lukasz Bugajski, Katarzyna Piwocka
The recently announced new methodologies to detect mRNA molecules in single cells offer opportunities for research, medicine and molecular diagnostics. The NanoFlare RNA Detection Probes are tools for characterizing RNA content (not localization) using fluorescence-based approaches in living cells. Combined with flow cytometry NanoFlares have expanded the available possibilities of quantitative analysis of mRNA level in a single cell. Herein we present, that the specific NanoFlare probes (SmartFlares), in some cases detect different amounts of mRNA compared to qPCR...
February 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28195814/in-response-to-bcr-abl-testing-by-polymerase-chain-reaction-in-patients-with-neutrophilia-the-william-beaumont-hospital-experience-and-the-case-for-rational-laboratory-test-requests
#7
https://www.readbyqxmd.com/read/28186602/-analysis-of-isodicentric-ph-chromosomes-in-chronic-myeloid-leukemia-blast-crisis
#8
Qian Li, Xiaoji Lin, Ying Lin, Rongxin Yao, Wu Huang, Handong Mei, Jian Gong, Hui Chen, Ningyan Teng
OBJECTIVE: To explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC). METHODS: Bone marrow aspirates of 2 patients with CML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations (CNV) were analyzed by single nucleotide polymorphism array (SNP array) in case 1. The results were confirmed with fluorescence in situ hybridization (FISH)...
February 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28184964/absorption-metabolism-and-excretion-of-14-c-ponatinib-after-a-single-oral-dose-in-humans
#9
Yihua E Ye, Caroline N Woodward, Narayana I Narasimhan
PURPOSE: Ponatinib is a novel tyrosine kinase inhibitor (TKI) specifically designed to inhibit native and mutated BCR-ABL. In the United States, ponatinib has received accelerated approval for adults with T315I-positive chronic myeloid leukemia (CML) or T315I (gatekeeper mutation)-positive, Philadelphia chromosome-positive, acute lymphoblastic leukemia (Ph + ALL), and patients with CML or Ph + ALL for whom no other TKI therapy is indicated. The objective of this phase 1, mass balance study was to evaluate the absorption, metabolism, and excretion of [(14)C]ponatinib in healthy subjects...
February 9, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28182037/janus-kinase-2-mutations-in-cases-with-bcr-abl-negative-chronic-myeloproliferative-disorders-from-turkey
#10
Ismail Yildiz, Osman Yokuş, Habip Gedik
OBJECTIVE: We aimed to investigate the frequency of Janus kinase 2 (JAK2) mutations in cases with chronic myeloproliferative disorders (CMDs), and the relationship between the presence of JAK2 mutation and leukocytosis and splenomegaly, retrospectively. MATERIALS AND METHODS: Patients, who were diagnosed with BCR-ABL-negative CMDs according to diagnosis criteria of the World Health Organization and followed up at the hematology clinic between 2013 and 2015, were investigated in terms of the frequency of JAK2 mutation in cases with CMDs, and the relationship between the presence of JAK2 mutation and leukocytosis and splenomegaly, retrospectively...
January 2017: Avicenna Journal of Medicine
https://www.readbyqxmd.com/read/28154167/in-vivo-knockdown-of-pathogenic-proteins-via-specific-and-nongenetic-iap-dependent-protein-erasers-snipers
#11
Nobumichi Ohoka, Keiichiro Okuhira, Masahiro Ito, Katsunori Nagai, Norihito Shibata, Takayuki Hattori, Osamu Ujikawa, Kenichiro Shimokawa, Osamu Sano, Ryokichi Koyama, Hisashi Fujita, Mika Teratani, Hirokazu Matsumoto, Yasuhiro Imaeda, Hiroshi Nara, Nobuo Cho, Mikihiko Naito
Many diseases, especially cancers, result from aberrant or over-expression of pathogenic proteins. Specific inhibitors against these proteins have shown remarkable therapeutic effects, but are limited mainly to enzymes. An alternative approach that may have utility in drug development relies on selective degradation of pathogenic proteins via small, chimeric molecules linking an E3 ubiquitin ligase to the targeted protein for proteasomal degradation. To this end, we recently developed a protein-knockdown system based on hybrid small-molecule SNIPERs (Specific and Nongenetic IAP-dependent Protein Erasers) that recruit inhibitor of apoptosis protein (IAP) ubiquitin ligases to specifically degrade targeted proteins...
February 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28154092/increased-peroxisome-proliferator-activated-receptor-gamma-activity-reduces-imatinib-uptake-and-efficacy-in-chronic-myeloid-leukemia-mononuclear-cells
#12
Jueqiong Wang, Liu Lu, Chung H Kok, Verity A Saunders, Jarrad M Goyne, Phuong Dang, Tamara M Leclercq, Timothy P Hughes, Deborah L White
Imatinib is actively transported by OCT-1 influx transporter, and low OCT-1 activity in diagnostic chronic myeloid leukemia blood mononuclear cells is significantly associated with poor molecular response to imatinib. Here we report that, in diagnostic chronic myeloid leukemia mononuclear cells and BCR-ABL1+ cell lines, peroxisome proliferator-activated receptor gamma agonists (GW1929, rosiglitazone, pioglitazone) significantly decrease OCT-1 activity; conversely, peroxisome proliferator-activated receptor gamma antagonists (GW9662, T0070907) increase OCT-1 activity...
February 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28153834/fall-of-the-mutants-t-cells-targeting-bcr-abl
#13
Premal Lulla, Helen E Heslop
No abstract text is available yet for this article.
February 2, 2017: Blood
https://www.readbyqxmd.com/read/28143387/development-of-a-predictive-pharmacophore-model-and-a-3d-qsar-study-for-an-in-silico-screening-of-new-potent-bcr-abl-kinase-inhibitors
#14
Eleni Vrontaki, Georgia Melagraki, Stella Voskou, Marios S Phylactides, Thomas Mavromoustakos, Marina Kleanthous, Antreas Afantitis
Chronic myelogenous leukemia (CML) is a myeloproliferative disorder, characterized, in most cases, by the presence of the Bcr-Abl fusion oncogene. Bcr-Abl is a constitutively active tyrosine kinase that is responsible for the malignant transformation. Targeting the Bcr-Abl kinase is an attractive treatment strategy for CML. First and second generation Bcr-Abl inhibitors have focused on targeting the ATP-binding domain of the kinase. Mutations in that region are relatively resistant to drug manipulation. Therefore, non-ATP-competitive agents have been recently developed and tested...
2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28140712/the-clinical-characteristics-and-prognostic-significance-of-aid-mir-181b-and-mir-155-expression-in-adult-patients-with-de-novo-b-cell-acute-lymphoblastic-leukemia
#15
Guangquan Zhou, Yang Cao, Weimin Dong, Yan Lin, Qi Wang, Wei Wu, Xiaoying Hua, Yun Ling, Xiaobao Xie, Shaoyan Hu, Jiannong Cen, Weiying Gu
This study aimed to investigate clinical characteristics and prognostic significance of activation-induced cytidine deaminase (AID) gene, miR-181b and miR-155 expression in de novo adult B-cell acute lymphoblastic leukemia (B-ALL) patients. Results showed that AID and miR-155 expression were higher in B-ALL patients than healthy controls, while miR-181b expression was lower in B-ALL patients. In addition, Ph(+) B-ALLs had higher AID expression than Ph(-) B-ALLs, and its high expression was associated with BCR-ABL...
January 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28140710/another-tyrosine-kinase-inhibitor-resistance-mutation-within-the-bcr-abl-kinase-domain-chasing-our-tails
#16
Jason B Kaplan, Leonidas C Platanias
No abstract text is available yet for this article.
January 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28128444/suppression-of-carboxylesterases-by-imatinib-mediated-by-the-downregulation-of-pregnane-x-receptor
#17
Wenjing Luo, Yu Xin, Xia Zhao, Feng Zhang, Changqing Liu, Hongwei Fan, Tao Xi, Jing Xiong
BACKGROUND AND PURPOSE: Imatinib mesylate (IM) is first-line anti-chronic myeloid leukemia (CML) therapy as a specific inhibitor of BCR-ABL tyrosine kinase. IM in combination with other drugs has been widely applied in CML treatment, thus the influence of IM on drug metabolism enzymes (DMEs) is crucial to be understood in suggesting rational drug administration. Carboxylesterases (CESs) are important enzymes catalyzing hydrolytic biotransformation and play vital roles in the metabolism of numerous clinical drugs...
January 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28128329/oridonin-triggers-chaperon-mediated-proteasomal-degradation-of-bcr-abl-in-leukemia
#18
Huilin Huang, Hengyou Weng, Bowen Dong, Panpan Zhao, Hui Zhou, Lianghu Qu
Inducing degradation of oncoproteins by small molecule compounds has the potential to avoid drug resistance and therefore deserves to be exploited for new therapies. Oridonin is a natural compound with promising antitumor efficacy that can trigger the degradation of oncoproteins; however, the direct cellular targets and underlying mechanisms remain unclear. Here we report that oridonin depletes BCR-ABL through chaperon-mediated proteasomal degradation in leukemia. Mechanistically, oridonin poses oxidative stress in cancer cells and directly binds to cysteines of HSF1, leading to the activation of this master regulator of the chaperone system...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28111465/differential-signaling-networks-of-bcr-abl-p210-and-p190-kinases-in-leukemia-cells-defined-by-functional-proteomics
#19
S Reckel, R Hamelin, S Georgeon, F Armand, Q Jolliet, D Chiappe, M Moniatte, O Hantschel
The two major isoforms of the oncogenic Bcr-Abl tyrosine kinase, p210 and p190, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p190 occurs in the majority of B-cell acute lymphoblastic leukemia. Differences in protein interactions and activated signaling pathways that may be associated with the different diseases driven by p210 and p190 are unknown. We have performed a quantitative comparative proteomics study of p210 and p190. Strong differences in the interactome and tyrosine phosphoproteome were found and validated...
January 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28103625/phase-ii-study-of-imatinib-based-chemotherapy-for-newly-diagnosed-bcr-abl-positive-acute-lymphoblastic-leukemia
#20
Shin Fujisawa, Shuichi Mizuta, Hideki Akiyama, Yasunori Ueda, Yasutaka Aoyama, Yoshihiro Hatta, Kazuhiko Kakihana, Nobuaki Dobashi, Isamu Sugiura, Yasushi Onishi, Tomoya Maeda, Kiyotoshi Imai, Shigeki Ohtake, Yasushi Miyazaki, Kazunori Ohnishi, Keitaro Matsuo, Tomoki Naoe
This study investigated the efficacy of imatinib based therapy with intensified consolidation therapy in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) to prevent early relapse. We conducted a phase II trial of imatinib-combined chemotherapy for newly diagnosed BCR-ABL-positive ALL in adults. Sixty-eight patients were included in the trial between October 2008 and December 2010. The median age was 49 years, with 28 patients >55 years of age. Sixty-five patients achieved CR (95...
January 19, 2017: American Journal of Hematology
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