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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
#1
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
#2
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
#3
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/28423649/stellettin-b-induces-apoptosis-in-human-chronic-myeloid-leukemia-cells-via-targeting-pi3k-and-stat5
#4
Yali Chen, Qianxiang Zhou, Lei Zhang, Yuxu Zhong, Guanwei Fan, Zhe Zhang, Ran Wang, Meihua Jin, Yuling Qiu, Dexin Kong
Novel agents are still urgently expected for therapy of chronic myeloid leukemia (CML). The in vitro anti-leukemia activity of Stellettin B (Stel B), a triterpenoid we isolated from marine sponge Jaspis stellifera, on human CML K562 and KU812 cells was recently investigated. Stel B inhibited K562 and KU812 cell proliferation with IC50 as 0.035 μM and 0.95 μM respectively. While no obvious cell cycle arrest was observed, apoptosis was induced in K562 cells after Stel B treatment. The Stel B-induced apoptosis might be in mitochondrial pathway, with increase of Bad and Bax, decrease of Bcl-2 and activation of caspase-9...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421151/extramedullary-relapse-in-a-cml-patient-after-allogeneic-stem-cell-transplantation
#5
Asu Fergun Yilmaz, Nur Soyer, Nazan Ozsan, Seckin Cagirgan, Ajda Gunes, Melda Comert, Fahri Sahin, Guray Saydam, Nur Selvi Gunel, Filiz Vural
Myeloid or granulocytic sarcoma (GS) is a tumoral lesion consisting of immature granulocytic cells. It is a rare entity during the course of CML patients especially after allogeneic stem cell transplantation (SCT). Relapse without bone marrow involvement is much rarer. We report a case of CML patient who relapsed with isolated granulocytic sarcoma after allogeneic SCT during cytogenetic and molecular remission. 28-year-old male was diagnosed as CML and allogeneic SCT was performed because of refractory disease to tyrosine kinase inhibitors...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28420426/genotypes-of-slc22a4-and-slc22a5-regulatory-loci-are-predictive-of-the-response-of-chronic-myeloid-leukemia-patients-to-imatinib-treatment
#6
Monika Jaruskova, Nikola Curik, Rajna Hercog, Vaclava Polivkova, Eliska Motlova, Vladimir Benes, Hana Klamova, Pavla Pecherkova, Petra Belohlavkova, Filip Vrbacky, Katerina Machova Polakova
BACKGROUND: Through high-throughput next-generation sequencing of promoters of solute carrier and ATP-binding cassette genes, which encode drug transporters, we aimed to identify SNPs associated with the response to imatinib administered for first-line treatment of patients with chronic myeloid leukemia. METHODS: In silico analysis using publicly available databases was done to select the SLC and ABC genes and their promoters for the next-generation sequencing. SNPs associated with the imatinib response were identified using Fisher's exact probability tests and subjected to the linkage disequilibrium analyses with regulatory loci of concerned genes...
April 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28420292/neuroendocrine-tumor-of-cecum-in-patient-treated-with-imatinib-mesylate-for-blastic-phase-of-chronic-myeloid-leukemia
#7
Sabina Novaković, Anamarija Kovač Peić, Hrvoje Holik, Božena Coha
Imatinib mesylate (IM), a tyrosine kinase inhibitor, is the treatment of choice in patients with chronic myeloid leukemia (CML). It is considered a very safe drug, with mostly mild and reversible side effects. Lately, it has been suggested that adverse events may occur after a long term. We report a case of a 72-year-old woman diagnosed with blastic phase of Philadelphia chromosome positive CML treated with IM for 28 months. The patient presented first with ascites as a side effect of the drug. When the ascites re-occurred, it was caused by neuroendocrine tumor (NET) with peritoneal carcinomatosis...
April 19, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28420097/synthesis-of-curcuminoids-and-evaluation-of-their-cytotoxic-and-antioxidant-properties
#8
María Concepción Lozada-García, Raúl G Enríquez, Teresa O Ramírez-Apán, Antonio Nieto-Camacho, Juan Francisco Palacios-Espinosa, Zeltzin Custodio-Galván, Olivia Soria-Arteche, Jaime Pérez-Villanueva
Curcumin (1) and ten derivatives (2-11) were synthesized and evaluated as cytotoxic and antioxidant agents. The results of primary screening by Sulforhodamine B assay against five human cancer cell lines (U-251 MG, glioblastoma; PC-3, human prostatic; HCT-15, human colorectal; K562, human chronic myelogenous leukemia; and SKLU-1, non-small cell lung cancer) allowed us to calculate the half maximal inhibitory concentration (IC50) values for the more active compounds against HCT-15 and K562 cell lines. Compounds 2 and 10 were the most active against both cell lines and were more active than curcumin itself...
April 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28418880/contributions-of-met-activation-to-bcr-abl1-tyrosine-kinase-inhibitor-resistance-in-chronic-myeloid-leukemia-cells
#9
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
#10
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
https://www.readbyqxmd.com/read/28416154/a-comparison-of-dicarbonyl-stress-and-advanced-glycation-endproducts-in-lifelong-endurance-athletes-vs-sedentary-controls
#11
Martijn F H Maessen, Casper G Schalkwijk, Rebecca J H M Verheggen, Vincent L Aengevaeren, Maria T E Hopman, Thijs M H Eijsvogels
OBJECTIVES: Dicarbonyl stress and high concentrations of advanced glycation endproducts (AGEs) relate to an elevated risk for cardiovascular diseases (CVD). Exercise training lowers the risk for future CVD. We tested the hypothesis that lifelong endurance athletes have lower dicarbonyl stress and AGEs compared to sedentary controls and that these differences relate to a better cardiovascular health profile. DESIGN: Cross-sectional study. METHODS: We included 18 lifelong endurance athletes (ATH, 61±7years) and 18 sedentary controls (SED, 58±7years) and measured circulating glyoxal (GO), methylglyoxal (MGO) and 3-deoxyglucosone (3DG) as markers of dicarbonyl stress...
March 23, 2017: Journal of Science and Medicine in Sport
https://www.readbyqxmd.com/read/28415816/targeting-the-pim-protein-kinases-for-the-treatment-of-a-t-cell-acute-lymphoblastic-leukemia-subset
#12
Sathish K R Padi, Libia A Luevano, Ningfei An, Ritu Pandey, Neha Singh, Jin H Song, Jon C Aster, Xue-Zhong Yu, Shikhar Mehrotra, Andrew S Kraft
New approaches are needed for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) who fail to achieve remission with chemotherapy. Analysis of the effects of pan-PIM protein kinase inhibitors on human T-ALL cell lines demonstrated that the sensitive cell lines expressed higher PIM1 protein kinase levels, whereas T-ALL cell lines with NOTCH mutations tended to have lower levels of PIM1 kinase and were insensitive to these inhibitors. NOTCH-mutant cells selected for resistance to gamma secretase inhibitors developed elevated PIM1 kinase levels and increased sensitivity to PIM inhibitors...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411847/the-molecular-revolution-in-cutaneous-biology-era%C3%A2-of-cytogenetics-and-copy-number%C3%A2-analysis
#13
REVIEW
Jürgen Bauer
Development of karyotyping techniques in the 1950s sparked groundbreaking reports of chromosomal aberrations in cancer, such as the Philadelphia chromosome in chronic myelogenous leukemia in 1960, followed by a number of others. Spatial resolution of karyotyping is limited and vital tumor cells are required for metaphase preparation. To overcome these limitations, DNA hybridization techniques were developed. In situ hybridization of radioactively or fluorescence labeled RNA probes onto tumor samples allowed the identification of specific genomic regions, translocations and copy number alterations...
May 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28410239/homoharringtonine-suppresses-imatinib-resistance-via-the-bcl-6-p53-pathway-in-chronic-myeloid-leukemia-cell-lines
#14
Qian Wang, Wei Ding, Yihan Ding, Jingjing Ma, Zhaoye Qian, Jingxian Shao, Yufeng Li
BACKGROUND: The anti-leukemic mechanism of homoharringtonine (HHT) differs from that of IM, and HHT is one of the most useful agents for use in patients with IM resistance or intolerance. The Bcl-6/p53 pathway has been shown to regulate the sensitivity of tumor cells to antitumor drugs. We tested whether HHT blocked the Bcl-6/p53 pathway in order to promote the apoptosis of IM-resistant cells in vitro and in vivo. RESULTS: Ph+ acute lymphoblastic leukemia (ALL) cells and IM-resistant chronic myeloid leukemia (CML) cells showed high expression of Bcl-6 protein...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409295/metal-chelator-tpen-selectively-induces-apoptosis-in-k562-cells-through-reactive-oxygen-species-signaling-mechanism-implications-for-chronic-myeloid-leukemia
#15
Luisa Rojas-Valencia, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio
Chronic myeloid leukemia (CML) is a hematologic disorder characterized by the constitutive expression of BCR-ABL tyrosine kinase. Although successful implementation of tyrosine kinase inhibitors for the treatment of CML remain a traditional choice for molecularly targeted therapy, some patients present primary or secondary resistance to such therapy. Therefore, alternative therapeutic strategies are required to treat resistant CML cells. Accordingly, new anti-proliferative and/or pro-apoptotic compounds would be needed for clinical treatment...
April 13, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28405921/the-role-of-early-molecular-response-in-the-management-of-chronic-phase-cml
#16
REVIEW
Patrick Harrington, Aytug Kizilors, Hugues de Lavallade
PURPOSE OF REVIEW: Although tyrosine kinase inhibitors (TKIs) spectacularly improve the disease burden and the overall survival of chronic myeloid leukemia patients, early identification of a subset of poor TKI responders has been recognized as a critical goal to prevent disease progression in these patients. We herein review the past and recent evidence on the impact of early response. RECENT FINDINGS: In the recent years, the achievement of an early molecular response (EMR, defined as 3-month BCR-ABL1 transcript <10% IS) has emerged as a useful tool to identify poor-risk patients...
April 12, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28405516/assessment-of-tumor-infiltrating-tcrv%C3%AE-9v%C3%AE-2-%C3%AE-%C3%AE-lymphocyte-abundance-by-deconvolution-of-human-cancers-microarrays
#17
Marie Tosolini, Frédéric Pont, Mary Poupot, François Vergez, Marie-Laure Nicolau-Travers, David Vermijlen, Jean-Emmanuel Sarry, Francesco Dieli, Jean-Jacques Fournié
Most human blood γδ cells are cytolytic TCRVγ9Vδ2(+) lymphocytes with antitumor activity. They are currently investigated in several clinical trials of cancer immunotherapy but so far, their tumor infiltration has not been systematically explored across human cancers. Novel algorithms allowing the deconvolution of bulk tumor transcriptomes to find the relative proportions of infiltrating leucocytes, such as CIBERSORT, should be appropriate for this aim but in practice they fail to accurately recognize γδ T lymphocytes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28404889/cryptic-bcr-abl-fusion-gene-as-variant-rearrangement-in-chronic-myeloid-leukemia-molecular-cytogenetic-characterization-and-influence-on-tkis-therapy
#18
Simona Luatti, Carmen Baldazzi, Giulia Marzocchi, Gaia Ameli, Maria Teresa Bochicchio, Simona Soverini, Fausto Castagnetti, Mario Tiribelli, Gabriele Gugliotta, Giovanni Martinelli, Michele Baccarani, Michele Cavo, Gianantonio Rosti, Nicoletta Testoni
At diagnosis, about 5% of Chronic Myeloid Leukemia (CML) patients lacks Philadelphia chromosome (Ph), despite the presence of the BCR/ABL rearrangement. Two mechanisms have been proposed about the occurrence of this rearrangement: the first one is a cryptic insertion between chromosomes 9 and 22; the second one involves two sequential translocations: a classic t(9;22) followed by a reverse translocation, which reconstitutes the normal morphology of the partner chromosomes. Out of 398 newly diagnosed CML patients, we selected 12 Ph-negative cases...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403949/racial-differences-in-circulating-levels-of-the-soluble-receptor-for-advanced-glycation-endproducts-in-middle-aged-and-older-adults
#19
Tina E Brinkley, Xiaoyan Leng, Barbara J Nicklas, Stephen B Kritchevsky, Jingzhong Ding, Dalane W Kitzman, W Gregory Hundley
BACKGROUND: Low levels of the soluble receptor for advanced glycation endproducts (sRAGE) have been implicated in a number of chronic diseases. Previous studies indicate that sRAGE levels are ~30% lower in Blacks compared to Whites. However, the reasons for these differences are unclear. PURPOSE: We aimed to identify predictors of circulating sRAGE biomarkers among Black and White adults at high cardiac risk. METHODS: Serum levels of total sRAGE, endogenous secretory RAGE (esRAGE), carboxymethyl-lysine (CML, a major RAGE ligand), and their ratios were measured in 99 Blacks and 454 Whites...
May 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28403785/apoptotic-effects-of-some-tetrahydronaphthalene-derivatives-on-k562-human-chronic-myelogenous-leukemia-cell-line
#20
Aslı Koç, Tulin Ozkan, Arzu Zeynep Karabay, Yalda Hekmatshoar, Ayse Selen Gurkan-Alp, Fugen Aktan, Zeliha Buyukbingol, Asuman Sunguroglu, Erdem Buyukbingol
BACKGROUND: Retinoids are synthetic and naturally occurring derivatives of vitamin A (retinol) which have been suggested to mediate inhibition of cancer cell growth and apoptosis. It has been reported that all trans retinoic acid (ATRA) exhibited suppressive effects on different types of leukemia including chronic myelogenous leukemia. OBJECTIVE: In the present study, we aim to find out the effects of 6 synthetic N-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-yl)-carboxamide derivatives (compound 6-12) on cell viability and apoptotic pathways in K562 human chronic myelogenous leukemia cell line...
April 12, 2017: Anti-cancer Agents in Medicinal Chemistry
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