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https://www.readbyqxmd.com/read/29780814/targeting-chronic-myeloid-leukemia-stem-cells-can-transcriptional-program-be-a-druggable-target-for-cancers
#1
REVIEW
Yosuke Masamoto, Mineo Kurokawa
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from acquisition of constitutively active BCR-ABL protein tyrosine kinase in a hematopoietic stem cell (HSC). Though tyrosine kinase inhibitors (TKIs) have changed a fatal disease into manageable disease, most patients cannot discontinue TKI treatment due to persistence of TKI-resistant leukemia stem cells (LSCs). Much effort has been made to find out factors or pathways specifically operating in LSCs to selectively target LSCs, with some promising results at least in preclinical models...
2018: Stem Cell Investigation
https://www.readbyqxmd.com/read/29755704/breastfeeding-in-patients-with-chronic-myeloid-leukaemia-case-series-with-measurements-of-drug-concentrations-in-maternal-milk-and-literature-review
#2
Ekaterina Chelysheva, Sergey Aleshin, Evgenia Polushkina, Roman Shmakov, Igor Shokhin, Ghermes Chilov, Anna Turkina
Breastfeeding in patients with chronic myeloid leukaemia (CML) during tyrosine kinase inhibitors (TKIs) therapy is not recommended but interruption of TKI treatment may cause the loss of remission. We studied the 3 cases of pregnancy and breastfeeding in women with CML and observed that stopping treatment without major molecular response may end in haematological relapse. The concentrations of nilotinib and imatinib in maternal milk were measured and nilotinib distribution in human breast milk was demonstrated for the first time...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29734071/the-rising-prevalence-of-chronic-myeloid-leukemia-in-france
#3
Marc Delord, Stéphanie Foulon, Jean-Michel Cayuela, Philippe Rousselot, Julia Bonastre
Outcomes in chronic myeloid leukemia (CML) have been dramatically improved since the emergence of imatinib and the subsequent generation of tyrosine kinase inhibitors (TKI) in the early 2000s. Indeed, CML is now associated with near-normal life expectancy for the majority of patients, provided they adhere to lifelong TKI-based treatment. This paradigm, in which CML can be regarded as a chronic disease, has inherent consequences on the prevalence of the disease. Our objective was to study CML prevalence trend in the French population from 1960 to 2060...
April 17, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29733872/experimental-and-integrative-analyses-identify-an-ets1-network-downstream-bcr-abl-in-chronic-myeloid-leukemia-cml
#4
Christophe Desterke, Maud Voldoire, Marie-Laure Bonnet, Nathalie Sorel, Sarah Pagliaro, Hind Rahban, Annelise Bennaceur Griscelli, Emilie Cayssials, Jean-Claude Chomel, Ali G Turhan
The BCR-ABL oncogene, hallmark of chronic myeloid leukemia (CML), has been shown to activate several signaling pathways in leukemic cells. The natural history of this disease has been radically modified by tyrosine kinase inhibitors (TKIs). However, resistance to several lines of TKI therapies and progression to blast crisis (BC) remain significant concerns. In order to identify novel signaling pathways induced by BCR-ABL, we performed a transcriptome analysis in BCR-ABL-expressing UT-7 cell line. More than 2000 genes differentially expressed between BCR-ABL-expressing and parental UT-7 cells were identified, and ETS1 was found to be the most up-regulated...
May 4, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29724897/targeting-hsp90-dimerization-via-the-c-terminus-is-effective-in-imatinib-resistant-cml-and-lacks-heat-shock-response
#5
Sanil Bhatia, Daniela Diedrich, Benedikt Frieg, Heinz Ahlert, Stefan Stein, Bertan Bopp, Franziska Lang, Tao Zang, Tobias Kröger, Thomas Ernst, Gesine Kögler, Andreas Krieg, Steffen Lüdeke, Hana Kunkel, Ana J Rodrigues Moita, Matthias U Kassack, Viktoria Marquardt, Friederike V Opitz, Marina Oldenburg, Marc Remke, Florian Babor, Manuel Grez, Andreas Hochhaus, Arndt Borkhardt, Georg Groth, Luitgard Nagel-Steger, Joachim Jose, Thomas Kurz, Holger Gohlke, Finn K Hansen, Julia Hauer
Heat shock protein 90 (HSP90) stabilizes many client proteins including BCR-ABL1 oncoprotein. BCR-ABL1 is the hallmark of CML in which treatment-free remission (TFR) is limited with clinical and economic consequences. Thus, there is an urgent need for novel therapeutics, which synergize with current treatment approaches. Several inhibitors targeting the N-terminal domain (NTD) of HSP90 are under investigation; however, side effects such as induction of heat shock response (HSR) and toxicity have so far precluded their FDA approval...
May 3, 2018: Blood
https://www.readbyqxmd.com/read/29719934/pre-treatment-evaluation-of-fret-based-drug-sensitivity-test-for-patients-with-cml-treated-with-dasatinib
#6
Takeshi Kondo, Mari Fujioka, Masumi Tsuda, Kazunori Murai, Kohei Yamaguchi, Takuto Miyagishima, Motohiro Shindo, Takahiro Nagashima, Kentaro Wakasa, Nozomu Fujimoto, Satoshi Yamamoto, Masakatsu Yonezumi, Souichi Saito, Shinji Sato, Kazuei Ogawa, Takaaki Chou, Reiko Watanabe, Yuichi Kato, Shuichiro Takahashi, Yoshiaki Okano, Joji Yamamoto, Masatsugu Ohta, Hiroaki Iijima, Koji Oba, Satoshi Kishino, Junichi Sakamoto, Yoji Ishida, Yusuke Ohba, Takanori Teshima
Tyrosine kinase inhibitors (TKIs) are used for primary therapy in patients with newly diagnosed chronic myeloid leukemia (CML). However, a reliable method for optimal selection of a TKI from the viewpoint of drug sensitivity of CML cells has not been established. We have developed a fluorescence resonance energy transfer (FRET)-based drug sensitivity test in which a CrkL-derived fluorescent biosensor efficiently quantifies the kinase activity of BCR-ABL of living cells and sensitively evaluates the inhibitory activity of a TKI against BCR-ABL...
May 2, 2018: Cancer Science
https://www.readbyqxmd.com/read/29703870/the-epidemiology-of-chronic-myeloid-leukaemia-in-southern-sarawak-borneo-island
#7
J W Kuan, S Melaine Michael
OBJECTIVES: There are very few published chronic myeloid leukaemia (CML) epidemiology studies in South-East Asia and no representative from Malaysia. METHODS: This is a cross-sectional study of adult CML patients (citizen) in a single but representative centre in southern Sarawak. RESULTS: Total 79 patients (Malay 39%, Chinese 30.4%, Iban 17.7%, Bidayuh 12.7%) were identified from the databases. Median age at diagnosis was younger, 40, compared to developed countries due to population structure...
April 2018: Medical Journal of Malaysia
https://www.readbyqxmd.com/read/29695943/bosutinib-in-chronic-myeloid-leukemia-patient-selection-and-perspectives
#8
REVIEW
Susanne Isfort, Tim H Brümmendorf
During recent years, the therapeutic landscape in chronic myeloid leukemia (CML) has changed significantly. Since the clinical introduction of tyrosine kinase inhibitors (TKIs) approximately 15 years ago, patients' concerns have shifted from reduced life expectancy toward long-term toxicities of TKI, depth of remission, and the probability of successful treatment discontinuation. Patients with newly diagnosed CML in chronic phase (at least with a Sokal score not exceeding intermediate) may now expect an almost normal life expectancy...
2018: Journal of Blood Medicine
https://www.readbyqxmd.com/read/29695383/allelic-polymorphisms-of-kirs-and-hlas-predict-favorable-responses-to-tyrosine-kinase-inhibitors-in-cml
#9
Hiroshi Ureshino, Takero Shindo, Hiroto Kojima, Yasushi Kusunoki, Yuki Miyazaki, Hidenori Tanaka, Hiroh Saji, Atsushi Kawaguchi, Shinya Kimura
Response to tyrosine kinase inhibitors (TKIs) is variable in chronic myeloid leukemia (CML), and elevated natural killer (NK) cells during TKI therapy are positively correlated with superior outcomes. NK cell function involves interactions of their killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I on target cells, and the avidity of KIR-HLA interactions depends on the combination of KIR and HLA alleles. We hypothesized that KIR and HLA polymorphisms may influence response to TKIs...
April 25, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29687320/tyrosine-kinase-inhibitors-in-the-treatment-of-chronic-phase-cml-strategies-for-frontline-decision-making
#10
REVIEW
James A Kennedy, Gabriela Hobbs
PURPOSE OF REVIEW: Over the past two decades, the introduction of tyrosine kinase inhibitors (TKIs) has transformed the treatment of chronic myeloid leukemia (CML). With four agents currently approved for frontline use in chronic-phase (CP) disease, it follows that treatment decision-making has been rendered more challenging. Here we will review recent advances that help inform the selection of a first-line TKI. RECENT FINDINGS: Extended follow-up of the seminal CML trials has demonstrated the long-term efficacy of TKIs, while also highlighting significant differences in their respective toxicity profiles and potency...
April 23, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29675611/ponatinib-as-second-line-treatment-in-chronic-phase-chronic-myeloid-leukemia-patients-in-real-life-practice
#11
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/29665902/-mean-corpuscular-volume-can-be-a-predictor-for-therapeutic-response-of-patients-with-chronic-myeloid-leukemia
#12
Luo Lu, Chun Qiao, Ming Hong, Yan-Ru Li, Liang-Qin Pan, Si-Xuan Qian, Yu Zhu, Jian-Yong Li
OBJECTIVE: The past studies found that the treatment of chronic myeloid leukemia (CML) with imatinib can induce the macrocytic anemia, moreover the incidence of anemia increases along with enhancement of imatinib concentration. This study was aimed to evaluate the potential relation of erythrocyte mean corpuscular volume (MCV) increase after the treatment with tyrosine kinase inhibitors (TKI) with the therapeutic response in patients with CML-chronic phase (CML-CP). METHODS: The clinical and hematologic data including MCV, molecular and cytogenetic response of 119 patients with CML-CP were collected after treatment with TKIs, and the relation of MCV changes after treatment with the clinical characteristics and therapeutic efficacy for patients with CML-CP was analyzed...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
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
#13
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/29660177/severe-adverse-events-by-tyrosine-kinase-inhibitors-decrease-survival-rates-in-patients-with-newly-diagnosed-chronic-phase-chronic-myeloid-leukemia
#14
Shuichi Ota, Toshihiro Matsukawa, Satoshi Yamamoto, Ito Shinichi, Motohiro Shindo, Kazuya Sato, Takeshi Kondo, Kyuhei Kohda, Hajime Sakai, Akio Mori, Tohru Takahashi, Hiroshi Ikeda, Hiroyuki Kuroda, Yoshihito Haseyama, Masaki Yamamoto, Takeo Sarashina, Makoto Yoshida, Ryoji Kobayashi, Mitsufumi Nishio, Toshimichi Ishihara, Yasuo Hirayama, Yasutaka Kakinoki, Hajime Kobayashi, Takashi Fukuhara, Masahiro Imamura, Mitsutoshi Kurosawa
OBJECTIVE: This multicenter cooperative study aimed to analyze the adverse events (AEs) associated with tyrosine kinase inhibitors (TKIs) used as initial treatment for chronic-phase chronic myeloid leukemia (CML-CP) and their impact on outcome. METHODS: We retrospectively evaluated 450 patients with CML-CP who received TKIs between 2004 and 2014. RESULTS: The 5-year overall survival (OS) and event-free survival (EFS) rates were 95.1% and 89...
April 16, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29651584/anxiety-and-depression-associated-with-tyrosine-kinase-inhibitor-discontinuation-in-patients-with-chronic-myeloid-leukemia
#15
Rintaro Sogawa, Sakiko Kimura, Ryota Yakabe, Yasuhito Mizokami, Masanobu Tasaki, Naoko Sueoka-Aragane, Yutaka Narisawa, Shinya Kimura
BACKGROUND: ABL tyrosine kinase inhibitors (TKIs) significantly changed the prognosis of patients with chronic myeloid leukemia (CML), and clinical trials demonstrated that TKIs can be discontinued in approximately 50% of patients after a period of deep molecular response (DMR). However, in some patients, TKI discontinuation leads to anxiety and depression. Here, we analysed the incidence of anxiety and depression in patients who stop TKI therapy. METHODS: Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS) in 32 patients with CML...
April 12, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29627787/tyrosine-kinase-inhibitor-induced-rapidly-progressive-vasculopathy-after-intracranial-stent-placement
#16
Ching-Jen Chen, Brian J Sorace, Aria Shakeri, Min S Park, Andrew M Southerland, Bradford B Worrall, M Yashar S Kalani
Tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) has been associated with progressive peripheral arterial disease and, more recently, rare cases of intracranial vascular stenosis have been reported. We report the fourth case of TKI treatment associated intracranial vasculopathy and rapid progression of intracranial vascular stenosis following intracranial stent placement. This was a 49-year-old woman who developed right-sided weakness, paresthesias, numbness, and speech difficulties 7 years following TKI treatment for CML...
April 7, 2018: Journal of Neurointerventional Surgery
https://www.readbyqxmd.com/read/29622860/laboratory-monitoring-of-chronic-myeloid-leukemia-in-patients-on-tyrosine-kinase-inhibitors
#17
REVIEW
Richa Chauhan, Sudha Sazawal, H P Pati
Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by translocation of genetic material from chromosome 9 to chromosome 22 to form a fusion gene (BCR-ABL1) that is responsible for abnormal tyrosine kinase activity and alteration of various downstream signaling pathways. In addition to morphological diagnosis of CML phase, it is essential to detect BCR-ABL1 fusion by either metaphase cytogenetics or reverse transcriptase polymerase chain reaction that also determines type of mRNA transcript...
April 2018: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29615434/tyrosine-kinase-inhibitor-induced-rapidly-progressive-vasculopathy-after-intracranial-stent-placement
#18
Ching-Jen Chen, Brian J Sorace, Aria Shakeri, Min S Park, Andrew M Southerland, Bradford B Worrall, M Yashar S Kalani
Tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) has been associated with progressive peripheral arterial disease and, more recently, rare cases of intracranial vascular stenosis have been reported. We report the fourth case of TKI treatment associated intracranial vasculopathy and rapid progression of intracranial vascular stenosis following intracranial stent placement. This was a 49-year-old woman who developed right-sided weakness, paresthesias, numbness, and speech difficulties 7 years following TKI treatment for CML...
April 3, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29593936/oral-effects-and-early-implant-survival-results-after-imatinib-discontinuation-therapy-for-chronic-myelogenous-leukemia-a-case-report
#19
Douglas R Dixon, Alaa Yassin
Introduction: Little is known regarding the success, failure, or complication rates of advanced implant procedures in patients after discontinuation therapy of long-term medications for the treatment of chronic myelogenous leukemia (CML). This case report presents initial results of a case involving implant placement in the mandible and maxilla as well as reduction of palatal oral pigmentation in a patient discontinuing long-term tyrosine kinase inhibitor (TKI) therapy for CML. Case Presentation: A 57-year-old male was referred to the Department of Periodontics, University of Washington, Seattle, Washington, for an assessment of edentulous areas (tooth sites #3 and #14) and failing tooth #19...
August 2017: Clinical Advances in Periodontics
https://www.readbyqxmd.com/read/29581839/excellent-outcomes-of-2g-tki-therapy-after-imatinib-failure-in-chronic-phase-cml-patients
#20
Mario Tiribelli, Massimiliano Bonifacio, Gianni Binotto, Alessandra Iurlo, Francesca Cibien, Elena Maino, Anna Guella, Gianluca Festini, Claudia Minotto, Ercole De Biasi, Federico De Marchi, Luigi Scaffidi, Luca Frison, Cristina Bucelli, Marta Medeot, Elisabetta Calistri, Rosaria Sancetta, Manuela Stulle, Nicola Orofino, Mauro Krampera, Filippo Gherlinzoni, Gianpietro Semenzato, Giovanni Pizzolo, Achille Ambrosetti, Renato Fanin
Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing imatinib. Direct comparisons between dasatinib and nilotinib are lacking, and few studies addressed the dynamics of deep molecular response (DMR) in a "real-life" setting. We retrospectively analyzed 163 patients receiving dasatinib ( n = 95) or nilotinib ( n = 68) as second-line therapy after imatinib...
March 6, 2018: Oncotarget
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