keyword
MENU ▼
Read by QxMD icon Read
search

TKI CML

keyword
https://www.readbyqxmd.com/read/28533818/a-novel-bcr-abl1-fusion-gene-with-genetic-heterogeneity-indicates-a-good-prognosis-in-a-chronic-myeloid-leukemia-case
#1
Fen Zhou, Runming Jin, Yu Hu, Heng Mei
BACKGROUND: Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28533480/deregulated-expression-of-mir-29a-3p-mir-494-3p-and-mir-660-5p-affects-sensitivity-to-tyrosine-kinase-inhibitors-in-cml-leukemic-stem-cells
#2
Simona Salati, Valentina Salvestrini, Chiara Carretta, Elena Genovese, Sebastiano Rontauroli, Roberta Zini, Chiara Rossi, Samantha Ruberti, Elisa Bianchi, Greta Barbieri, Antonio Curti, Fausto Castagnetti, Gabriele Gugliotta, Gianantonio Rosti, Micaela Bergamaschi, Agostino Tafuri, Enrico Tagliafico, Roberto Lemoli, Rossella Manfredini
The development of Imatinib mesylate (IM), which targets the oncogenic BCR-ABL fusion protein, has greatly improved the outcome of Chronic Myeloid Leukemia (CML) patients. However, BCR-ABL-positive progenitors can be detected in CML patients in complete cytogenetic response. Several evidence suggests that CML stem cells are intrinsically resistant to Tyrosine Kinase Inhibitors (TKI), and therefore they represent the most likely candidate responsible for disease relapse.In this work, we investigated the microRNA (miRNA) expression profile of different subpopulations of CML Leukemic Stem Cells (LSCs): Lin-CD34+CD38- and Lin-CD34-CD38- cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521421/an-unusual-translocation-t-1-11-q21-q23-in-a-case-of-chronic-myeloid-leukemia-with-a-cryptic-philadelphia-chromosome
#3
Leandro Germán Gutiérrez, María Fernanda Noriega, Alejandro Laudicina, Mariana Quatrin, Raquel María Bengió, Irene Larripa
Chronic myeloid leukemia (CML) is characterized by the translocation t(9;22)(q34;q11) [Philadelphia (Ph) chromosome). Although not frequently occurring, additional chromosome abnormalities (ACAs) can be detected at diagnosis and a number have been associated with an adverse cytogenetic and molecular outcome. The present study reports a case of CML presenting with the translocation t(1;11)(q21;q23) and a cryptic Ph chromosome. The presence of ACAs could generate greater genetic instability, promoting the emergence of further alterations...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28511567/treating-the-chronic-phase-chronic-myeloid-leukemia-patient-which-tki-when-to-switch-and-when-to-stop
#4
Ami B Patel, Brandon W Wilds, Michael W Deininger
With the discovery of imatinib mesylate nearly 20 years ago, tyrosine kinase inhibitors (TKIs) were found to be effective in chronic myeloid leukemia (CML). TKI therapy has since revolutionized the treatment of CML and has served as a paradigm of success for targeted drug therapy in cancer. Several new TKIs for CML have been approved over the last two decades that exhibit improved potency over imatinib and have different off-target profiles, providing options for individualized therapy selection. Areas covered: Current management of chronic phase CML, including guidance on the sequential use of imatinib and newer-generation TKIs and evolving treatment strategies such as TKI discontinuation...
May 22, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28508322/use-patterns-of-first-line-inhibitors-of-tyrosine-kinase-and-time-to-change-to-second-line-therapy-in-chronic-myeloid-leukemia
#5
Jorge Enrique Machado-Alba, Manuel Enrique Machado-Duque
Background Chronic myeloid leukemia (CML) has a low incidence but a high burden of disease, and is treated with high-cost tyrosine kinase inhibitors (TKI). Objective To determine the time from the start of a first-line TKI until it passes to second-line, and to establish the reasons for the change of therapy time. Setting Patients with Philadelphia-positive CML treated with some TKI. Methods Retrospective cohort study, between January 1 2007 and July 31 2015, with information obtained from medical records, the time to change initial drugs to secondline therapy, and the reasons for change, were identified...
May 15, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28501913/chronic-myeloid-leukemia-immunobiology-and-novel-immunotherapeutic-approaches
#6
Emilie Cayssials, Francois Guilhot
Imatinib has revolutionized the treatment and prognosis of chronic myeloid leukemia (CML) with survival rates now approaching those of the age-matched healthy population. To be able to discontinue tyrosine kinase inhibitor (TKI) treatment, it is necessary to develop complementary therapies to target minimal residual disease. Recent findings by a number of investigators in both CML mouse models and CML patients offer evidence that many factors in the leukemic microenvironment can collectively contribute to immune escape, including expansion of myeloid-derived suppressor cells, programmed death-1/programmed death-1 ligand interactions resulting in T-cell impairment, expression of soluble suppressive factors such as soluble CD25, and down-regulation of MHC molecules by CML cells...
May 13, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28501737/the-bcr-abl-tyrosine-kinase-inhibitor-nilotinib-stimulates-expression-of-il-1%C3%AE-in-vascular-endothelium-in-association-with-downregulation-of-mir-3p
#7
Masumi Sukegawa, Xiangmin Wang, Chie Nishioka, Bin Pan, Kailin Xu, Hiroshi Ohkawara, Yoichi Hamasaki, Masayuki Mita, Kenichi Nakamura, Masatoshi Okamoto, Hiromi Shimura, Masatsugu Ohta, Takayuki Ikezoe
BCR/ABL tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis for in dividuals with chronic myeloid leukemia (CML). However, many patients treated with TKIs suffer from TKI-related complications. In particular, vascular events such as peripheral artery occlusive disease have become aserious clinical problem for patients who receive the TKI, nilotinib. At present, the molecular mechanisms by which TKIs cause vascular endothelial cell insults remain unknown.This study explored the effects of the TKIs, imatinib, nilotinib and dasatinib, on vascular endothelial cells in vitro, and found that only nilotinib induced expression of interleukin-1β (IL-1β) by vascular endothelial cells...
May 5, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28484463/immune-effector-recovery-in-chronic-myeloid-leukemia-and-treatment-free-remission
#8
REVIEW
Amy Hughes, Agnes S M Yong
Chronic myeloid leukemia (CML) is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors (TKIs) represent the standard of care for CML patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy. TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (DMR, BCR-ABL1 ≤ 0...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28484170/chronic-myeloid-leukemia-and-nk-cell-immunity
#9
Hiroshi Ureshino, Takero Shindo, Hidenori Tanaka, Shinaya Kimura
BCR-ABL1 tyrosine kinase inhibitors (TKIs) have dramatically improved the long-term outcomes of patients with chronic myelogenous leukemia (CML). Notably, approximately half of patients with a sustained deep molecular response experienced treatment free remission (TFR) even after discontinuation of TKI. Although antitumor immunity by natural killer (NK) cells might contribute to the effects of TKI and TFR in CML, the details of their actions have not as yet been elucidated. Recently, several reports have raised the possibility that the killer immunoglobulin-like receptor (KIR), a highly polymorphic NK cell receptor, may play important roles, because polymorphic patterns of KIR were shown to be associated with the intensity of clinical responses and outcomes in TKI-treated CML patients...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28454362/growth-of-tyrosine-kinase-inhibitor-resistant-philadelphia-positive-acute-lymphoblastic-leukemia-role-of-bone-marrow-stromal-cells
#10
Cheng Zhang, Xi Zhang, Shi-Jie Yang, Xing-Hua Chen
Human bone marrow stromal cells (hBMSCs) may contribute to the growth of tyrosine kinase inhibitor (TKI)-resistant chronic myelogenous leukemia (CML). However, there are certain differences in biology between CML and Philadelphia-positive acute lymphoblastic leukemia (Ph(+) ALL). Little is known about the role and mechanism of hBMSCs on the growth of TKI-resistant Ph(+) ALL. The current study co-cultured hBMSCs with the TKI-resistant SUP-B15. Next, the proliferation of SUP-B15 was detected using a Cell Counting Kit-8...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28452984/frequent-somatic-mutations-in-epigenetic-regulators-in-newly-diagnosed-chronic-myeloid-leukemia
#11
E Togasaki, J Takeda, K Yoshida, Y Shiozawa, M Takeuchi, M Oshima, A Saraya, A Iwama, K Yokote, E Sakaida, C Hirase, A Takeshita, K Imai, H Okumura, Y Morishita, N Usui, N Takahashi, S Fujisawa, Y Shiraishi, K Chiba, H Tanaka, H Kiyoi, K Ohnishi, S Ohtake, N Asou, Y Kobayashi, Y Miyazaki, S Miyano, S Ogawa, I Matsumura, C Nakaseko, T Naoe
Although tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing to identify somatic mutations in 24 patients with newly diagnosed chronic phase CML who were registered in the JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1 fusion gene (median 8, range 1-17)...
April 28, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28446318/-research-progress-of-homoharringtonine-effect-on-im-resistant-chronic-myelogenous-leukemia-review
#12
Qian Wang, Yu-Feng Li
Homoharringtonine(HHT) is an alkaloid with anti-tumor activity, having a good therapeutic effect on chronic myeloid leukemia(CML), and its toxicity is much lower than other anti-cancer drugs. However, the remarkable therapeutic efficacy of imatinib on CML treatment made HHT to be forgotten gradually. Today, the omacetaxine mepesuccinate, a semisynthetic form of HHT, display a good clinical response to TKI-resistant CML patients. Therefore, the HHT again attracts more attention from the medical field. Here, the clinical effects of HHT on IM-resistant CML patients and its mechanism are briefly reviewed...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446278/-clinical-analysis-for-42-imatinib-resistant-patients-with-chronic-myelogenous-leukemia
#13
Xi Liu, Si-Lin Gan, Jie Ma, Yan-Fang Liu, Xin-Sheng Xie, Zhong-Xing Jiang, Yuan-Dong Cheng, Hui Sun
OBJECTIVE: To analyze the kinase mutation ratio, related factors, effectiveness and safety of the second generation drugs for imatinib-resistant patients with chronic myeloid leukemia(CML). METHODS: COX proportional hazard regression model was used for unvariate and multvariate analysis of various factors affecting the kinase mutation and for evaluating the effectiveness and safety of second generation tyrosine kinase inhibitor(TKI). RESULTS: 13 kinds of mutation were detected in 19 out of 42 cases for 22 times, including 4 times of F359V, 3 times of E255K, 2 time for F359C, F317L, T315I, Y253H, 1 time for D256R, C250R, D276G, F486S, M244V, Y256H and G250E, 3 cases with mixed mutations...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28444644/ponatinib-in-japanese-patients-with-philadelphia-chromosome-positive-leukemia-a-phase-1-2-study
#14
Arinobu Tojo, Taiichi Kyo, Kazuhito Yamamoto, Hirohisa Nakamae, Naoto Takahashi, Yukio Kobayashi, Tetsuzo Tauchi, Shinichiro Okamoto, Koichi Miyamura, Kiyohiko Hatake, Hiromi Iwasaki, Itaru Matsumura, Noriko Usui, Tomoki Naoe, Meera Tugnait, Narayana I Narasimhan, Stephanie Lustgarten, Heinrich Farin, Frank Haluska, Kazuma Ohyashiki
In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2)...
April 25, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28444623/treatment-adherence-in-chronic-myeloid-leukaemia-patients-receiving-tyrosine-kinase-inhibitors
#15
Anna Rychter, Piotr Jerzmanowski, Adam Hołub, Zofia Specht-Szwoch, Violetta Kalinowska, Urszula Tęgowska, Ilona Seferyńska, Agnieszka Kołkowska-Leśniak, Ewa Lech-Marańda, Joanna Góra-Tybor
Failure to comply with treatment recommendations is very common in patients, but still poorly recognised by doctors. The current practice of using oral therapy on a large scale has been increasingly adopted for cancer patients. Chronic myeloid leukaemia (CML) is just such an example, where the introduction of taking new oral medications, the tyrosine kinase BCR-ABL inhibitors (TKI), has now revolutionised the treatment. The aim of our study was to assess treatment adherence in a group of Polish CML patients (a survey was conducted on 140 patient aged ≥18 years) treated with oral TKI (imatinib, dasatinib and nilotinib) taking into account the following variables: gender, age, education, place of residence, family circumstances and duration of therapy...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28431398/decreased-calpain-activity-in-chronic-myeloid-leukemia-impairs-apoptosis-by-increasing-survivin-in-myeloid-progenitors-and-xiap1-in-differentiating-granulocytes
#16
Weiqi Huang, Ling Bei, Elizabeth E Hjort, Elizabeth A Eklund
Chronic Myeloid Leukemia (CML) is characterized by translocations between chromosomes 9 and 22, resulting in expression of Bcr-abl oncogenes. Although the clinical course of CML was revolutionized by development of Bcr-abl-directed tyrosine kinase inhibitors (TKIs), CML is not cured by these agents. Specifically, the majority of subjects relapsed in clinical trials attempting TKI discontinuation, suggesting persistence of leukemia stem cells (LSCs) even in molecular remission. Identifying mechanisms of CML-LSC persistence may suggest rationale therapeutic targets to augment TKI efficacy and lead to cure...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424749/development-of-asymmetric-facial-depigmentation-in-a-patient-treated-with-dasatinib-with-new-onset-hypovitaminosis-d-case-report-and-review-of-the-literature
#17
Kirsten C Webb, Magdalena Harasimowicz, Monica Janeczek, Jodi Speiser, James Swan, Rebecca Tung
Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) used to treat imatinib-resistant chronic myelogenous leukemia (CML), as well as other Philadelphia chromosome-positive lymphoproliferative disorders. While the most commonly reported cutaneous side effects with this therapy include a morbilliform eruption, skin exfoliation, and skin irritation, pigmentary abnormalities have also been observed, albeit much more rarely. We present the case of a 72-year-old South Asian male with CML who presented with new-onset hypopigmentation of his face and scalp three years after a dose increase of dasatinib therapy, in the setting of newly discovered borderline hypovitaminosis D...
2017: Case Reports in Dermatological Medicine
https://www.readbyqxmd.com/read/28423730/the-sclttaxbcr-abl-transgenic-mouse-model-closely-reflects-the-differential-effects-of-dasatinib-on-normal-and-malignant-hematopoiesis-in-chronic-phase-cml-patients
#18
Claudia Schubert, Nicolas Chatain, Till Braunschweig, Mirle Schemionek, Kristina Feldberg, Melanie Hoffmann, Olli Dufva, Satu Mustjoki, Tim H Brümmendorf, Steffen Koschmieder
The second generation tyrosine kinase inhibitor (TKI) dasatinib is a clinically approved drug for chronic myeloid leukemia (CML) as well as Ph+ acute lymphoblastic leukemia. In addition to its antileukemic effects, dasatinib was shown to impact on normal hematopoiesis and cells of the immune system.Due to the fact that the murine in vivo studies so far have not been performed in a chronic-phase CML model under steady-state conditions, our aim was to study the hematopoietic effects of dasatinib (20 mg/kg p.o...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418880/contributions-of-met-activation-to-bcr-abl1-tyrosine-kinase-inhibitor-resistance-in-chronic-myeloid-leukemia-cells
#19
Masanobu Tsubaki, Tomoya Takeda, Toshiki Kino, Kazuko Sakai, Tatsuki Itoh, Motohiro Imano, Takashi Nakayama, Kazuto Nishio, Takao Satou, Shozo Nishida
Resistance to the breakpoint cluster region-abelson 1 (BCR-ABL1) tyrosine kinase inhibitor (TKI) imatinib poses a major problem when treating chronic myeloid leukemia (CML). Imatinib resistance often results from a secondary mutation in BCR-ABL1. However, in the absence of a mutation in BCR-ABL1, the basis of BCR-ABL1-independent resistance must be elucidated. To gain insight into the mechanisms of BCR-ABL1-independent imatinib resistance, we performed an array-based comparative genomic hybridization. We identified various resistance-related genes, and focused on MET...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416739/tki-rotation-induced-persistent-deep-molecular-response-in-multi-resistant-blast-crisis-of-ph-cml
#20
Peter Valent, Susanne Herndlhofer, Mathias Schneeweiß, Bernd Boidol, Anna Ringler, Stefan Kubicek, Karoline V Gleixner, Gregor Hoermann, Emir Hadzijusufovic, Leonhard Müllauer, Wolfgang R Sperr, Giulio Superti-Furga, Christine Mannhalter
In chronic myeloid leukemia (CML) resistance against one or more BCR-ABL1 tyrosine kinase inhibitors (TKI) remains a clinical challenge. Preclinical data suggest that TKI combinations may overcome resistance. We report on a heavily pre-treated 78 year-old female patient with CML who developed multi-resistant blast crisis with bone marrow fibrosis and a Ph- clone. Treatment with ponatinib resulted in blast cell clearance, decrease in fibrosis, and disappearance of BCR-ABL1, but also in severe thrombocytopenia with bleedings requiring platelet transfusions...
April 4, 2017: Oncotarget
keyword
keyword
104047
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"