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https://www.readbyqxmd.com/read/29316665/towards-comprehension-of-the-abcb1-p-glycoprotein-role-in-chronic-myeloid-leukemia
#1
REVIEW
Raquel C Maia, Flavia C Vasconcelos, Paloma S Souza, Vivian M Rumjanek
Abstract: The introduction of imatinib (IM), a BCR-ABL1 tyrosine kinase inhibitor (TKI), has represented a significant advance in the first-line treatment of chronic myeloid leukemia (CML). However, approximately 30% of patients need to discontinue IM due to resistance or intolerance to this drug. Both resistance and intolerance have also been observed in treatment with the second-generation TKIs-dasatinib, nilotinib, and bosutinib-and the third-generation TKI-ponatinib. The mechanisms of resistance to TKIs may be BCR-ABL1-dependent and/or BCR-ABL1-independent...
January 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29316075/monitoring-tki-therapeutic-responses-with-the-panel-of-metabolic-biomarkers-in-the-chronic-myeloid-leukemia-patients
#2
Bingyu Yang, Chang Wang, Yiyu Xie, Liangjing Xu, Xiaojin Wu, Depei Wu
To investigate the potential biomarkers associated with Chronic Myeloid Leukemia (CML), reveal the metabolite changes related to the continuous phases of tyrosine kinase inhibitors (TKI) and find the potential biomarkers associated with treatment effects. 52 patients with CML and matched 26 healthy people were enrolled as discovery set. Another 194 randomly selected CML patients treated with TKI were chosen as external validation set. Plasma samples from the patients and controls were profiled by using gas chromatography-mass spectrometry (GC-MS) based metabonomic approach...
January 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29305630/chronic-myeloid-leukemia-patients-in-tunisia-epidemiology-and-outcome-in-the-imatinib-era-a-multicentric-experience
#3
Raihane Ben Lakhal, Hela Ghedira, Hatem Bellaaj, Yosra Ben Youssef, Samia Menif, Zeineb Manai, Manel Bedoui, Amel Lakhal, Fehmi M'Sadek, Moez Elloumi, Abderrahmane Khélif, Neila Ben Romdhane, Mohamed Adnène Laatiri, Tarek Ben Othmen, Balkis Meddeb
Data are limited in developing countries regarding the clinicopathologic features and response to therapy of chronic myeloid leukemia (CML) in the era of imatinib (IM). The objective of this study is to report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400 mg daily as frontline therapy, and to determine imatinib's efficacy and safety. From October 2002 to December 2014, 410 CML patients were treated with IM in six Tunisian departments of hematology...
January 6, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29299123/inhibition-of-sdf-1-induced-migration-of-oncogene-driven-myeloid-leukemia-by-the-l-rna-aptamer-spiegelmer-nox-a12-and-potentiation-of-tyrosine-kinase-inhibition
#4
Ellen L Weisberg, Martin Sattler, Abdel Kareem Azab, Dirk Eulberg, Anna Kruschinski, Paul W Manley, Richard Stone, James D Griffin
Resistance to targeted tyrosine kinase inhibitors (TKI) remains a challenge for the treatment of myeloid leukemias. Following treatment with TKIs, the bone marrow microenvironment has been found to harbor a small pool of surviving leukemic CD34+ progenitor cells. The long-term survival of these leukemic cells has been attributed, at least in part, to the protective effects of bone marrow stroma. We found that the NOX-A12 'Spiegelmer', an L-enantiomeric RNA oligonucleotide that inhibits SDF-1α, showed in vitro and in vivo activity against BCR-ABL- and FLT3-ITD-dependent leukemia cells...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296906/cytogenetics-based-risk-prediction-of-blastic-transformation-of-chronic-myeloid-leukemia-in-the-era-of-tki-therapy
#5
Zimu Gong, L Jeffrey Medeiros, Jorge E Cortes, Zi Chen, Lan Zheng, Yan Li, Shi Bai, Pei Lin, Roberto N Miranda, Jeffrey L Jorgensen, Timothy J McDonnell, Wei Wang, Hagop M Kantarjian, Shimin Hu
The high fatality of patients with blast phase (BP) chronic myeloid leukemia (CML) necessitates identification of high-risk (HR) patients to prevent onset of BP. Here, we investigated the risk of BP based on additional chromosomal abnormality (ACA) profiles in a cohort of 2326 CML patients treated with tyrosine kinase inhibitors (TKIs). We examined the time intervals from initial diagnosis to ACA emergence (interval 1), from ACA emergence to onset of BP (interval 2), and survival after onset of BP (interval 3)...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288559/omitting-cytogenetic-assessment-from-routine-treatment-response-monitoring-in-cml-is-safe
#6
Inge G P Geelen, Noortje Thielen, Jeroen J W M Janssen, Mels Hoogendoorn, Tanja J A Roosma, Peter J M Valk, Otto Visser, Jan J Cornelissen, Peter E Westerweel
OBJECTIVES: The monitoring of response in chronic myeloid leukemia (CML) is of great importance to identify patients failing their treatment in order to adjust TKI choice and thereby prevent progression to advanced stage disease. Cytogenetic monitoring has a lower sensitivity, is expensive, and requires invasive bone marrow sampling. Nevertheless, chronic myeloid leukemia guidelines continue to recommend performing routine cytogenetic response assessments, even when adequate molecular diagnostics are available...
December 29, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29284347/real-world-treatment-patterns-in-chronic-myeloid-leukemia-patients-newly-initiated-on-tyrosine-kinase-inhibitors-in-an-u-s-integrated-healthcare-system
#7
Nazia Rashid, Han A Koh, Kathy J Lin, Brian Stwalley, Eugene Felber
Purpose To evaluate treatment patterns in patients diagnosed with incident chronic myelogenous leukemia (CML) newly initiating therapy with imatinib, dasatinib, or nilotinib. Patients were followed to determine switching and discontinuation rates. Factors associated with switching or discontinuation from index TKI therapy, reasons for discontinuation based on electronic chart notes, and frequency of laboratory monitoring were assessed during the follow-up period. Methods A retrospective cohort study was conducted in chronic myelogenous leukemia patients aged ≥ 18 years who were identified from the Kaiser Permanente Southern California (KPSC) Cancer Registry database during the study time period of 1 January 2007 to 12 December 2013...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29242991/mechanisms-of-resistance-to-targeted-therapies-in-chronic-myeloid-leukemia
#8
Federico Lussana, Tamara Intermesoli, Paola Stefanoni, Alessandro Rambaldi
Patients with newly diagnosed chronic myeloid leukemia (CML) usually received as first-line treatment a first- or second-generation tyrosine kinase inhibitor (TKI). Although initial responses are high, therapy fails in up to 40% of patients and initial response is lost within 2 years in approximately 25% of patients. In the last few years, intensive efforts have been spent to explain treatment failure, and different mechanisms of resistance have been identified, ranging from BCR-ABL1 kinase domain mutations to lack of adherence to therapy...
December 15, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29228749/the-bcl2l11-deletion-polymorphism-is-not-associated-with-imatinib-resistance-in-chronic-myeloid-leukemia-patients-meta-analysis
#9
Jinyun Xu, Jiaowei Gu, Yan Zhao, Huihua Meng, Li'an Du, Ruibo Zhang, Hao Jiang, Jianming Luo
A common deletion polymorphism of the gene Bcl-2 like protein 11 (BCL2L11, BIM) has been reported to cause tyrosine kinase inhibitors (TKIs) resistance in several malignant tumors. However, the conclusions were not consistent in chronic myeloid leukemia (CML) individuals. In order to obtain a reliable conclusion, we systematically searched PubMed, Embase, Web of Science, Chinese Biomedical Database, and China National Knowledge Infrastructure and performed the meta-analysis. Six published articles contain 760 East Asian patients were identified from these electronic databases...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29224320/-comparative-study-of-cytogenetic-response-evaluated-by-conventional-banding-analysis-and-fluorescence-in-situ-hybridization-in-chronic-myeloid-leukemia-patients-during-tyrosine-kinase-inhibitor-treatment
#10
Z Wang, N Li, L Gao, L Feng, Y Z Qin, H Dang, Y Shi, Q He, Q Jiang, H Jiang, Y Y Lai
Objective: To compare the cytogenetic response detected by conventional banding analysis (CBA) and fluorescence in situ hybridization (FISH) and to explore the correlation between the cytogenetic and molecular response in chronic myeloid leukemia (CML) patients during tyrosine kinase inhibitor (TKI) treatment. Methods: CBA, FISH and real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) methods were performed to detect the cytogenetic and molecular response simultaneously in 504 bone marrow samples from 367 CML patients who received TKI treatment...
November 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29222245/novel-approaches-to-therapy-in-cml
#11
REVIEW
Ravi Bhatia
Treatment with tyrosine kinase inhibitors (TKIs) results in remission and prolongation of survival in most chronic myeloid leukemia (CML) patients but fails to eliminate the leukemia stem cells (LSCs) responsible for disease development and propagation. This accounts for the clinical observation that TKI discontinuation leads to rapid leukemia relapse. Most patients require continued treatment to prevent relapse, with associated risk of relapse, toxicity, teratogenic effects, financial burden, and noncompliance...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222244/cardiovascular-care-of-patients-with-chronic-myeloid-leukemia-cml-on-tyrosine-kinase-inhibitor-tki-therapy
#12
REVIEW
Mary C Barber, Michael J Mauro, Javid Moslehi
Cardiovascular (CV) health has emerged as an important consideration in patients with chronic myeloid leukemia (CML) because of improved prognosis. Indeed, the success of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has increased the focus on survivorship and late toxicity in oncological care. Survivorship issues in this population include CV disease prevention, given its prevalence in the general population. The introduction of BCR-ABL1 TKIs represented a unique concept of indefinite cancer therapy, only recently evolving to include "treatment-free remission...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222243/treatment-free-remission-in-cml-who-how-and-why
#13
REVIEW
Francois-Xavier Mahon
Chronic myeloid leukemia (CML) is the best example of successful targeted therapy. Today, the overall survival of patients with CML treated by using tyrosine kinase inhibitors (TKIs) is very close to that of the healthy population. The current question is: how can we further ameliorate the clinical outcome of patients with CML? Clinical trials have shown that some patients with CML in the chronic phase who achieve sustained deep molecular responses on TKI therapy can safely suspend therapy with no evidence of relapse...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29218828/monocytic-myeloid-derived-suppressor-cells-as-prognostic-factor-in-chronic-myeloid-leukaemia-patients-treated-with-dasatinib
#14
Cesarina Giallongo, Nunziatina L Parrinello, Piera La Cava, Giuseppina Camiolo, Alessandra Romano, Marina Scalia, Fabio Stagno, Giuseppe A Palumbo, Roberto Avola, Giovanni Li Volti, Daniele Tibullo, Francesco Di Raimondo
Myeloid suppressor cells are a heterogeneous group of myeloid cells that are increased in patients with chronic myeloid leukaemia (CML) inducing T cell tolerance. In this study, we found that therapy with tyrosine kinase inhibitors (TKI) decreased the percentage of granulocytic MDSC, but only patients treated with dasatinib showed a significant reduction in the monocytic subset (M-MDSC). Moreover, a positive correlation was observed between number of persistent M-MDSC and the value of major molecular response in dasatinib-treated patients...
December 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29212733/successful-ovarian-stimulation-for-fertility-preservation-in-a-patient-with-chronic-myeloid-leukemia-switch-from-nilotinib-to-interferon-%C3%AE
#15
Smaranda Gazdaru, Lucien Perey, Anne Rosselet, Patrice Mathevet, Yves Chalandon, Nicolas Vulliemoz
The development of tyrosine-kinase inhibitors (TKIs) has improved survival of patients with chronic myeloid leukemia (CML). Some patients may become resistant to TKIs and require hematopoietic stem cell transplant (HSCT) that is highly gonadotoxic. Fertility preservation with ovarian stimulation might be indicated but is challenging if patients need to remain on TKIs until HSCT because TKIs may compromise follicular development and response to ovarian stimulation. We report the case of a patient with CML resistant to TKI and planned for an HSCT, in which treatment by TKI was replaced by interferon-α before and during ovarian stimulation for fertility preservation...
December 6, 2017: Oncologist
https://www.readbyqxmd.com/read/29200684/the-role-of-mutation-testing-in-patients-with-chronic-myeloid-leukemia-in-chronic-phase-after-imatinib-failure-and-their-outcomes-after-treatment-modification-single-institutional-experience-over-13-years
#16
Puligundla Krishna Chaitanya, Karnam Ashok Kumar, Bala Stalin, Gundeti Sadashivudu, Maddali Lakshmi Srinivas
Introduction: BCR-ABL1 kinase domain mutations represent the most frequent mechanism of resistance to tyrosine kinase inhibitor (TKI) therapy, being detected in 40%-50% of imatinib-resistant patients with chronic myeloid leukemia in chronic phase (CML-CP). Over 100 BCR-ABL1 single-point mutations have been reported in patients with imatinib-resistant CML. There were few studies reported from India on BCR-ABL kinase mutations in imatinib failure patients. We present our data on imatinib resistance mutation analysis (IRMA) and use of imatinib dose hike and 2nd-generation TKI at our institute...
July 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29198338/ponatinib-in-chronic-myeloid-leukemia-cml-consensus-on-patient-treatment-and-management-from-a-european-expert-panel
#17
REVIEW
Martin C Müller, Francisco Cervantes, Henrik Hjorth-Hansen, Jeroen J W M Janssen, Dragana Milojkovic, Delphine Rea, Gianantonio Rosti
Five tyrosine kinase inhibitors (TKIs) are currently approved in the European Union for treatment of chronic myeloid leukemia (CML) and all have considerable overlap in their indications. While disease-specific factors such as CML phase, mutational status, and line of treatment are key to TKI selection, other important features must be considered, such as patient-specific comorbidities and TKI safety profiles. Ponatinib, the TKI most recently approved, has demonstrated efficacy in patients with refractory CML, but is associated with an increased risk of arterial hypertension, sometimes severe, and serious arterial occlusive and venous thromboembolic events...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29179634/azacytidine-in-combination-with-tyrosine-kinase-inhibitors-induced-durable-responses-in-patients-with-advanced-phase-chronic-myelogenous-leukemia
#18
Mathilde Ruggiu, Florence Oberkampf, David Ghez, Pascale Cony-Makhoul, Florence Beckeriche, Isabelle Cano, Anne L Taksin, Omar Benbrahim, Stéphanie Ghez, Hassan Farhat, Sophie Rigaudeau, Noémie de Gunzburg, Diane Lara, Christine Terre, Victoria Raggueneau, Isabel Garcia, Marc Spentchian, Stéphane De Botton, Philippe Rousselot
Although the tyrosine kinase inhibitor (TKI) era has brought great improvement in outcome in chronic myelogenous leukemia (CML), prognosis of accelerated phase or myeloid blast crisis patients or of de novo Philadelphia chromosome-positive acute myeloid leukemia remains poor. We conducted a retrospective study on patients with advanced phase disease treated with a TKI and azacytidine. Sixteen patients were eligible. Median age was 64.9 years, the median number of previous therapies was 2.5 lines, and median follow-up was 23...
November 28, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29165716/targeting-bcr-abl-independent-tki-resistance-in-chronic-myeloid-leukemia-by-mtor-and-autophagy-inhibition
#19
Rebecca Mitchell, Lisa E M Hopcroft, Pablo Baquero, Elaine K Allan, Kay Hewit, Daniel James, Graham Hamilton, Arunima Mukhopadhyay, Jim O'Prey, Alan Hair, Junia V Melo, Edmond Chan, Kevin M Ryan, Véronique Maguer-Satta, Brian J Druker, Richard E Clark, Subir Mitra, Pawel Herzyk, Franck E Nicolini, Paolo Salomoni, G Vignir Helgason
Background: Imatinib and second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib have statistically significantly improved the life expectancy of chronic myeloid leukemia (CML) patients; however, resistance to TKIs remains a major clinical challenge. Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment...
November 20, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29151902/coexistence-of-p210bcr-abl-and-cbf%C3%AE-myh11-fusion-genes-in-myeloid-leukemia-a-report-of-4-cases
#20
Yuan-Yuan Wang, Wen-Jing Ding, Feng Jiang, Zi-Xing Chen, Jian-Nong Cen, Xiao-Fei Qi, Jian-Ying Liang, Dan-Dan Liu, Jin-Lan Pan, Su-Ning Chen
Numerous acquired molecular and cytogenetic abnormalities are strongly associated with hematological malignancies. The breakpoint cluster region-ABL proto-oncogene 1 (BCR-ABL) rearrangement leads to a p210 chimeric protein in typical chronic myeloid leukemia (CML), whereas 17-25% of patients with acute lymphocytic leukemia and 0.9-3% patients with de novo acute myeloid leukemia (AML) carry a p190BCR-ABL fusion protein. Cases of patients with AML/CML carrying two specific primary molecular changes, BCR-ABL and core binding factor-β-myosin heavy chain 11 (CBFβ-MYH11) fusion genes have been rarely reported...
November 2017: Oncology Letters
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