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Chronic myeloid leukemia

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https://www.readbyqxmd.com/read/28829353/chemokines-as-a-conductor-of-bone-marrow-microenvironment-in-chronic-myeloid-leukemia
#1
REVIEW
Naofumi Mukaida, Yamato Tanabe, Tomohisa Baba
All blood lineage cells are generated from hematopoietic stem cells (HSCs), which reside in bone marrow after birth. HSCs self-renew, proliferate, and differentiate into mature progeny under the control of local microenvironments including hematopoietic niche, which can deliver regulatory signals in the form of bound or secreted molecules and from physical cues such as oxygen tension and shear stress. Among these mediators, accumulating evidence indicates the potential involvement of several chemokines, particularly CXCL12, in the interaction between HSCs and bone marrow microenvironments...
August 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28828991/a-virtual-screening-approach-for-the-identificationof-high-affinity-small-molecules-targeting-bcr-abl1-inhibitors-for-the-treatment-of-chronic-myeloid-leukemia
#2
Saphy Sharda, Palash Sarmandal, Srinivas Bandaru, Pravin Patil, Ruchi Shukla, Amrita Jain, Anudeep Sharma, Tanmay Vyas, Tajamul Hussain, Anuraj Nayarisseri
CML originates due to reciprocal translocation in Philadelphia chromosome leading to formation of fusion product BCR-ABL which constitutively activates tyrosine kinase signaling pathways eventually abnormal proliferation of granulocytic cells. As a therapeutic strategy, BCR-ABL inhibitors have been clinically approved which terminates its phosphorylation activity and retards cancer progression. However,number of patients develops resistance to inhibitors which demand for discovery of new inhibitors. Given the drawbacks of present inhibitors, by high throughput virtual screening approaches, present study pursues to identify high affinity compounds targeting BCR-ABL1 anticipated to have safer pharmacological profiles...
August 21, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28826859/tet2-restrains-inflammatory-gene-expression-in-macrophages
#3
Alyssa H Cull, Brooke Snetsinger, Rena Buckstein, Richard A Wells, Michael J Rauh
Tet methylcytosine dioxygenase 2 (TET2) is one of the earliest and most frequently mutated genes in clonal hematopoiesis of aging (CHIP) and myeloid cancers, including myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). TET2 catalyzes the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, leading to DNA demethylation. TET2 also affects transcription by recruiting histone modifiers. Inactivating TET2 mutations cause epigenetic dysregulation, clonal hematopoietic stem cell dominance and monocytic lineage skewing...
August 18, 2017: Experimental Hematology
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
#4
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/28821556/dasatinib-reversibly-disrupts-endothelial-vascular-integrity-by-increasing-non-muscle-myosin-ii-contractility-in-a-rock-dependent-manner
#5
Anna Kreutzman, Beatriz Colom-Fernández, Ana Marcos Jiménez, Mette Ilander, Carlos Cuesta-Mateos, Yaiza Perez-García, Cristina Delgado Arévalo, Oscar Brück, Henna Hakanen, Jani Saarela, Alvaro Ortega-Carrión, Ana de Rosendo, Alba Juanes-García, Juan Luis Steegmann, Satu Mustjoki, Miguel Vicente-Manzanares, Cecilia Muñoz-Calleja
Purpose: Dasatinib is a short-acting dual ABL/SRC family tyrosine kinase inhibitor (TKI), which is frequently used to treat chronic myeloid leukemia. Although very effective, dasatinib often displays severe adverse effects, including pleural effusions and increased risk of bleeding primarily in the gastrointestinal tract. The actual causes of these side effects are currently undetermined. We hypothesize that endothelial cells (ECs) that line the inner walls of blood vessels and control the traffic to the underlying tissues, might be involved...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28815757/first-line-treatment-selection-and-early-monitoring-patterns-in-chronic-phase-chronic-myeloid-leukemia-in-routine-clinical-practice-simplicity
#6
Stuart L Goldberg, Jorge Cortes, Carlo Gambacorti-Passerini, Rüdiger Hehlmann, H Jean Khoury, Mauricette Michallet, Ron Paquette, Bengt Simonsson, Teresa Zyczynski, Aimee Foreman, Elisabetta Abruzzese, David Andorsky, Aart Beeker, Pascale Cony-Makhoul, Richard Hansen, Elza Lomaia, Eduardo Olavarria, Michael Mauro
Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n=416), dasatinib (n=418) or nilotinib (n=408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1,242 prospective patients (enrolled October 01 2010-September 02 2015) are reported...
August 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28813698/caspase-independent-pathway-is-related-to-nilotinib-cytotoxicity-in-cultured-cardiomyocytes
#7
Qinghui Yang, Chunhui Zhang, Hong Wei, Zenghui Meng, Guangnan Li, Yuanyuan Xu, Yanjun Chen
BACKGROUND/AIMS: Cardiotoxicity is a predominant side-effect of nilotinib during chronic myeloid leukemia treatment. The underlying molecular mechanism remains unclear. The role of autophagy and mitochondrial signaling was investigated in nilotinib-treated cardiac H9C2 cells. METHODS: Cytotoxicity was assessed using Cell Death Detection kit. Immunoblot and immunofluorescence staining was performed, and cathepsin B and caspase3 activity was assessed in nilotinib-treated H9C2 cells with or without distinct pathway inhibitor or specific siRNA...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28813500/telomere-biology-and-telomerase-mutations-in-cirrhotic-patients-with-hepatocellular-carcinoma
#8
Flávia S Donaires, Natália F Scatena, Raquel M Alves-Paiva, Joshua D Podlevsky, Dhenugen Logeswaran, Barbara A Santana, Andreza C Teixeira, Julian J-L Chen, Rodrigo T Calado, Ana L C Martinelli
Telomeres are repetitive DNA sequences at linear chromosome termini, protecting chromosomes against end-to-end fusion and damage, providing chromosomal stability. Telomeres shorten with mitotic cellular division, but are maintained in cells with high proliferative capacity by telomerase. Loss-of-function mutations in telomere-maintenance genes are genetic risk factors for cirrhosis development in humans and murine models. Telomerase deficiency provokes accelerated telomere shortening and dysfunction, facilitating genomic instability and oncogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28812528/acute-leukemia-in-horses
#9
Carina J Cooper, Stefan M Keller, Luis G Arroyo, Joanne Hewson, Daniel Kenney, Dorothee Bienzle
Leukemia is broadly divided into acute and chronic lymphocytic and myeloid types based on the proportion of blasts, morphology of cells, and expression of specific antigens on neoplastic cells. Classifying leukemia in horses can be challenging if blasts predominate and since few antibodies to identify cell types are available. The objective of this study was to describe in detail the clinical and pathologic features of acute leukemia in horses. Twelve horses ranging from 0.2 to 25.9 years of age were diagnosed with acute leukemia...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28810322/-comparison-of-generic-and-original-imatinib-in-the-treatment-of-newly-diagnosed-patients-with-chronic-myelogenous-leukemia-in-chronic-phase-a-multicenter-retrospective-clinical-study
#10
H Jiang, L T Zhi, M Hou, J X Wang, D P Wu, X J Huang
Objective: To evaluate the efficacy and safety of generic imatinib (Genike, Chiatai Tianqing Pharmaceutical Group Co., Ltd.) and imatinib (Glevic, Novartis, Switzerland) in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) . Methods: A retrospective study of 323 CML-CP patients (205 in Glivec treatment group and 118 in Genike group) who were ≥ 18 years old receiving imatinib monotherapy over the period of June 2013 to March 2016 was done to compare the differences of cytogenetics, molecular curative effect, survival, and adverse reactions between the two groups...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#11
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28803825/cardiovascular-events-after-exposure-to-nilotinib-in-chronic-myeloid-leukemia-long-term-follow-up
#12
Nazanin Aghel, Jeffrey Howard Lipton, Eshetu G Atenafu, Dennis Dong Hwan Kim, Diego Hernan Delgado
INTRODUCTION: Nilotinib is a highly effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML). However, reports of cardiovascular toxicities caused by nilotinib have recently raised critical concerns. The aim of the present study was to evaluate the incidence of cardiovascular events (CVEs) and frequency of asymptomatic peripheral arterial disease (PAD) after long-term exposure to nilotinib. PATIENTS AND METHODS: In the present retrospective cohort, we evaluated the incidence of CVEs in 63 CML patients treated with nilotinib...
July 15, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28803005/safety-and-feasibility-of-therapeutic-platelet-depletion-with-spectra-optia-in-a-pregnant-woman
#13
Roman Małachowski, Olga Grzybowska-Izydorczyk, Nelly Besson, Anna Szmigielska-Kapłon, Mateusz Nowicki, Agnieszka Wierzbowska
INTRODUCTION: Thrombocytapheresis is an alternative treatment beneficial in rare circumstances, when cytoreductive agents are contraindicated, drug therapy gave no response or the expected response would be too slow. Here we present a case of a pregnant woman who underwent 5 thrombocytaphereses using Spectra Optia device to reduce circulating platelets (PLT) count and prepare for Cesarian section. PATIENT CHARACTERISTICS AND PERFORMED TREATMENT: A 39-year-old woman with diagnosed chronic myeloid leukemia (CML) was treated with interferon because of too high PLT count...
July 27, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28801986/persistent-detection-of-alternatively-spliced-bcr-abl-variant-results-in-a-failure-to-achieve-deep-molecular-response
#14
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/28796569/cost-effectiveness-of-kinase-inhibitors-for-hematologic-malignancies-a-systematic-and-critical-review
#15
Monia Marchetti
Several genetic disruptions lead to constitutive activation of those kinases leukemic cells depend on for survival and proliferation. Kinase inhibitors (KI) are major therapeutic innovations for chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and myelofibrosis (MF) providing a relevant improvement of quality-adjusted survival in patients with high-risk or refractory disease. CML patients are being treated with first-generation KI imatinib since many years, achieving expected survivals longer than 10 years...
August 10, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28795321/nkg2d-gene-polymorphisms-are-associated-with-disease-control-of-chronic-myeloid-leukemia-by-dasatinib
#16
Ryujiro Hara, Makoto Onizuka, Erika Matsusita, Eri Kikkawa, Yoshihiko Nakamura, Hiromichi Matsushita, Daisuke Ohgiya, Hiromichi Murayama, Shinichiro Machida, Ken Ohmachi, Yukari Shirasugi, Yoshiaki Ogawa, Hiroshi Kawada, Kiyoshi Ando
A recent study reported that treatment-free remission (TFR) of chronic myeloid leukemia (CML) after dasatinib (Das) treatment was significantly associated with natural killer (NK) cell proliferation in the peripheral blood. However, biomarkers to predict lymphocytosis or successful TFR are not well characterized. In order to clarify individual differences in NK cell responses among patients treated with Das, we retrospectively analyzed the association between polymorphisms in the natural killer group 2D receptor [NKG2D; also known as killer cell lectin like receptor K1 (KLRK1)] gene and clinical outcomes in 31 patients treated with Das as first-line treatment for CML...
August 9, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28792265/sustained-molecular-response-in-chronic-myeloid-leukemia-deep-responders-treated-with-low-dose-tyrosine-kinase-inhibitors
#17
Emilie Cayssials, Florence Tartarin, Joëlle Guilhot, Nathalie Sorel, Jean Claude Chomel, Xavier Leleu, François Guilhot
No abstract text is available yet for this article.
August 9, 2017: Leukemia & Lymphoma
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
#18
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/28774214/the-safety-of-bosutinib-for-the-treatment-of-chronic-myeloid-leukemia
#19
Jee Hyun Kong, H J Khoury, Audrey Sunwha Kim, Brittany Gray Hill, Vamsi Kota
Introduction Tyrosine kinase inhibitors (TKIs) are a potentially lifelong treatment for patients with chronic myeloid leukemia (CML). Adverse events (AEs) associated with TKIs are significant impediments in the daily life of patients that can impact compliance, and efficacy. Areas covered This is a review on safety of bosutinib in the treatment of chronic phase CML. Data is extracted from the latest updates of bosutinib phase I/II and III trials. Expert opinion Bosutinib is an effective agent against all phases of CML presently approved for the treatment in patients with resistance or intolerance to prior TKI therapy...
August 3, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28772207/bone-marrow-mesenchymal-stromal-cell-msc-gene-profiling-in-chronic-myeloid-leukemia-cml-patients-at-diagnosis-and-in-deep-molecular-response-induced-by-tyrosine-kinase-inhibitors-tkis
#20
Djamel Aggoune, Nathalie Sorel, Marie-Laure Bonnet, Jean-Michel Goujon, Karin Tarte, Olivier Hérault, Jorge Domenech, Delphine Réa, Laurence Legros, Hyacinthe Johnson-Ansa, Philippe Rousselot, Emilie Cayssials, Agnès Guerci-Bresler, Annelise Bennaceur-Griscelli, Jean-Claude Chomel, Ali G Turhan
Although it has been well-demonstrated that bone marrow mesenchymal stromal cells (MSCs) from CML patients do not belong to the Ph1-positive clone, there is growing evidence that they could play a role in the leukemogenesis process or the protection of leukemic stem cells from the effects of tyrosine kinase inhibitors (TKIs). The aim of the present study was to identify genes differentially expressed in MSCs isolated from CML patients at diagnosis (CML-MSCs) as compared to MSCs from healthy controls. Using a custom gene-profiling assay, we identified six genes over-expressed in CML-MSCs (BMP1, FOXO3, MET, MITF, NANOG, PDPN), with the two highest levels being documented for PDPN (PODOPLANIN) and NANOG...
July 26, 2017: Leukemia Research
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