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https://www.readbyqxmd.com/read/28926427/dna-methylation-targeted-drugs
#1
Elodie M Da Costa, Gabrielle McInnes, Annie Beaudry, Noël J-M Raynal
Targeting DNA hypermethylation, using nucleoside analogs, is an efficient approach to reprogram cancer cell epigenome leading to reduced proliferation, increased differentiation, recognition by the immune system, and ultimately cancer cell death. DNA methyltransferase inhibitors have been approved for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myelogenous leukemia. To improve clinical efficacy and overcome mechanisms of drug resistance, a second generation of DNA methyltransferase inhibitors has been designed and is currently in clinical trials...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28919910/chloroma-of-the-testis-in-a-patient-with-a-history-of-acute-myeloid-leukemia
#2
Mohammad Hossein Sanei, Matin Shariati
Chloroma, or granulocytic sarcoma, is a rare extramedullary solid hematologic cancer, found concomitant with acute myeloid leukemia. It is infrequently associated with other myeloproliferative disorders or chronic myelogenous leukemia. Chloroma of the testis after allogeneic bone marrow transplantation is particularly sparsely represented in the literature. It is suggested that an appropriate panel of marker studies be performed along with clinical correlation and circumspection to avoid misleading conclusions...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/28892084/validation-of-the-revised-ipss-at-transplant-in-patients-with-myelodysplastic-syndrome-transformed-acute-myelogenous-leukemia-receiving-allogeneic-stem-cell-transplantation-a-retrospective-analysis-of-the-ebmt-chronic-malignancies-working-party
#3
C Scheid, L de Wreede, A van Biezen, C Koenecke, G Göhring, L Volin, J Maertens, J Finke, J Passweg, D Beelen, J J Cornelissen, M Itälä-Remes, P Chevallier, N Russell, E Petersen, N Milpied, C Richard Espiga, A Peniket, J Sierra, G Mufti, C Crawley, J H Veelken, P Ljungman, J Y Cahn, E P Alessandrino, T de Witte, M Robin, N Kröger
The International Prognostic Scoring System has been revised (IPSS-R) to predict prognosis of patients with myelodysplastic syndromes at diagnosis. To validate the use of the IPSS-R assessed before transplant rather than at diagnosis we performed a retrospective analysis of the EBMT database. A total of 579 patients had sufficient information available to calculate IPSS-R at transplant. Median overall survival (OS) from transplant was significantly different according to IPSS-R: very low 23.6 months, low 55...
September 11, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28859112/mathematical-modelling-as-a-proof-of-concept-for-mpns-as-a-human-inflammation-model-for-cancer-development
#4
Morten Andersen, Zamra Sajid, Rasmus K Pedersen, Johanne Gudmand-Hoeyer, Christina Ellervik, Vibe Skov, Lasse Kjær, Niels Pallisgaard, Torben A Kruse, Mads Thomassen, Jesper Troelsen, Hans Carl Hasselbalch, Johnny T Ottesen
The chronic Philadelphia-negative myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms which ultimately may transform to acute myelogenous leukemia. Most recently, chronic inflammation has been described as an important factor for the development and progression of MPNs in the biological continuum from early cancer stage to the advanced myelofibrosis stage, the MPNs being described as "A Human Inflammation Model for Cancer Development". This novel concept has been built upon clinical, experimental, genomic, immunological and not least epidemiological studies...
2017: PloS One
https://www.readbyqxmd.com/read/28844837/prostaglandin-e1-and-its-analog-misoprostol-inhibit-human-cml-stem-cell-self-renewal-via-ep4-receptor-activation-and-repression-of-ap-1
#5
Fengyin Li, Bing He, Xiaoke Ma, Shuyang Yu, Rupali R Bhave, Steven R Lentz, Kai Tan, Monica L Guzman, Chen Zhao, Hai-Hui Xue
Effective treatment of chronic myelogenous leukemia (CML) largely depends on the eradication of CML leukemic stem cells (LSCs). We recently showed that CML LSCs depend on Tcf1 and Lef1 factors for self-renewal. Using a connectivity map, we identified prostaglandin E1 (PGE1) as a small molecule that partly elicited the gene expression changes in LSCs caused by Tcf1/Lef1 deficiency. Although it has little impact on normal hematopoiesis, we found that PGE1 treatment impaired the persistence and activity of LSCs in a pre-clinical murine CML model and a xenograft model of transplanted CML patient CD34(+) stem/progenitor cells...
September 7, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28839396/nilotinib-induced-keratosis-pilaris-associated-with-alopecia-areata-and-eyebrow-thinning
#6
Maya Halabi Tawil, Rana El Khoury, Roland Tomb, Marwan Ghosn
Tyrosine kinase enzymes are an attractive target for anticancer therapies. Tyrosine kinase inhibitors (TKI) are well tolerated; somehow severe systemic side effects are rarely seen during treatment. Toxicities of skin and appendages may lead to poor compliance, psychosocial inconvenience, and drug interruption. Changes of the hair can arise following cures with TKI. Nilotinib, a second-generation TKI, has been responsible for various cutaneous side effects including different clinical presentations of alopecia (scarring and nonscarring forms)...
April 2017: International Journal of Trichology
https://www.readbyqxmd.com/read/28830803/acute-promyelocytic-leukemia-in-a-patient-with-chronic-lymphocytic-leukemia-a-case-report
#7
Prajwal Boddu, Ellen Schlette, Beenu Thakral, Guillin Tang, Naveen Pemmaraju, Tapan Kadia, Alessandra Ferrajoli, Farhad Ravandi, William Wierda, Nitin Jain
Chronic lymphocytic leukemia (CLL) is known to be associated rarely with myeloid malignancies such as acute myelogenous leukemia. In this article, we report an extremely rare occurrence of acute promyelocytic leukemia in a patient with CLL. A 71-year-old man first presented to our clinic with a diagnosis of CLL and worsening motor neuropathy symptoms. It was suspected that his CLL might be contributing to the neuropathy as a paraneoplastic syndrome, and he was treated with rituximab monotherapy in weekly doses for the 1st month and monthly treatments thereafter...
August 16, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28819285/phosphorylation-of-sos1-on-tyrosine-1196-promotes-its-rac-gef-activity-and-contributes-to-bcr-abl-leukemogenesis
#8
S Gerboth, E Frittoli, A Palamidessi, F C Baltanas, S Mogjiborahman, J Rappsilber, C Giuliani, F Troglio, Y Rolland, G Pruneri, S Kreutmair, I Pallavicini, M Zobel, M Cinquanta, S Minucci, C Gomez, E Santos, A L Illert, G Scita
Son of Sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the small GTPases RAC and RAS. While the molecular mechanisms of RAS GEF catalysis have been unveiled, how SOS1 acquires RAC GEF activity and what is the physio-pathological relevance of this activity is much less understood. Here, we show that SOS1 is tyrosine phosphorylated on Y1196 by ABL. Phosphorylation of Y1196 controls SOS1 inter-molecular interaction, is required to promote the exchange of nucleotides on RAC in vitro, and for PDGF activation of RAC and RAC-dependent actin remodeling and cell migration...
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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
#9
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/28808015/a-p53-dependent-response-limits-the-viability-of-mammalian-haploid-cells
#10
Teresa Olbrich, Cristina Mayor-Ruiz, Maria Vega-Sendino, Carmen Gomez, Sagrario Ortega, Sergio Ruiz, Oscar Fernandez-Capetillo
The recent development of haploid cell lines has facilitated forward genetic screenings in mammalian cells. These lines include near-haploid human cell lines isolated from a patient with chronic myelogenous leukemia (KBM7 and HAP1), as well as haploid embryonic stem cells derived from several organisms. In all cases, haploidy was shown to be an unstable state, so that cultures of mammalian haploid cells rapidly become enriched in diploids. Here we show that the observed diploidization is due to a proliferative disadvantage of haploid cells compared with diploid cells...
August 29, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28797620/extended-follow-up-of-patients-treated-with-bendamustine-for-lymphoid-malignancies
#11
Mara Penne, Maryam Sarraf Yazdy, Kruti Sheth Nair, Bruce D Cheson
INTRODUCTION: Bendamustine, typically in combination with rituximab, is an effective treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma. Despite its acceptable short-term toxicity profile, long-term toxicities are less well established. This study investigated the long-term adverse effects of bendamustine and responses to subsequent treatments. PATIENTS AND METHODS: Charts of 194 patients were retrospectively reviewed; 54% had received prior treatment (76% attained complete response [CR] or partial response [PR])...
June 30, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28767087/novel-methylselenoesters-as-antiproliferative-agents
#12
Nuria Díaz-Argelich, Ignacio Encío, Daniel Plano, Aristi P Fernandes, Juan Antonio Palop, Carmen Sanmartín
Selenium (Se) compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH₃SeH) being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH₃SeH. The fifteen compounds follow Lipinski's Rule of Five and with exception of compounds 1 and 14, present better drug-likeness values than the positive control methylseleninic acid...
August 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28752075/mir-155-effectively-induces-apoptosis-in-k562-philadelphia-positive-cell-line-through-upregulation-of-p27kip1
#13
Mahdi Edalati Fathabad, Morteza Karimipoor, Shaban Alizadeh, Asghar Abdoli, Amir Atashi, Mahtab Sayadi
Introduction: Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by the Philadelphia chromosome translocation, at (9; 22), which results in BCR-ABL fusion tyrosine kinase oncoprotein. This fusion induces down-regulation of miR-155. Upregulation of miR-155 can influence cell fate via the effect on p27kip1 and apoptosis. The aim of this study was to induce apoptosis in K562 CML cell line by overexpression of miR-155. Methods: The K562 cell line was transfected with pLenti-III-pre mir155-GFP constructs through electroporation...
2017: BioImpacts: BI
https://www.readbyqxmd.com/read/28744011/nk-cell-dynamics-and-association-with-molecular-response-in-early-chronic-phase-chronic-myelogenous-leukemia-cml-cp-patients-treated-with-nilotinib
#14
S Sopper, S Mustjoki, B T Gjertsen, F Giles, A Hochhaus, J J W M Janssen, K Porkka, D Wolf
No abstract text is available yet for this article.
July 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28730166/impact-of-chromosomal-rearrangement-upon-dna-methylation-patterns-in-leukemia
#15
Hyang-Min Byun, Shahrooz Eshaghian, Dan Douer, Jonathen Trent, Guillermo Garcia-Manero, Ravi Bhatia, Kim Siegmund, Allen S Yang
Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the BCR-ABL translocation t(9:22), in establishing DNA methylation profiles in cancer. Materials and methods We compared DNA methylation of 1,505 selected promoter CpGs in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34+ hematopoietic stem cells transfected with BCR-ABL, and other tumors without BCR-ABL (acute promyelocytic leukemia (APL) and gastrointestinal stromal tumors (GIST)...
2017: Open Medicine (Warsaw, Poland)
https://www.readbyqxmd.com/read/28729178/elevated-cardiovascular-disease-risk-in-patients-with-chronic-myelogenous-leukemia-seen-in-community-based-oncology-practices-in-the-united-states
#16
Anna D Coutinho, Dinara Makenbaeva, Eileen Farrelly, Pamela B Landsman-Blumberg, Daniel Lenihan
INTRODUCTION: Current National Comprehensive Cancer Network guidelines recommend that comorbidities, including cardiovascular disease (CVD), be considered when selecting tyrosine kinase inhibitors for the treatment of chronic myelogenous leukemia (CML). We report here the prevalence of CVD and its risk factors in patients with CML treated by community-based United States (US) oncologists. PATIENTS AND METHODS: Adult patients with a confirmed diagnosis of CML and ≥ 1 encounter after the first date of CML diagnosis in an electronic medical record database between January 1, 2005 and October 31, 2014 were enrolled...
June 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28719608/cholesterol-esterification-inhibition-and-imatinib-treatment-synergistically-inhibit-growth-of-bcr-abl-mutation-independent-resistant-chronic-myelogenous-leukemia
#17
Shovik Bandyopadhyay, Junjie Li, Elie Traer, Jeffrey W Tyner, Amy Zhou, Stephen T Oh, Ji-Xin Cheng
Since the advent of tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, and dasatinib, chronic myelogenous leukemia (CML) prognosis has improved greatly. However, ~30-40% of patients develop resistance to imatinib therapy. Although most resistance is caused by mutations in the BCR-ABL kinase domain, 50-85% of these patients develop resistance in the absence of new mutations. In these cases, targeting other pathways may be needed to regain clinical response. Using label-free Raman spectromicroscopy, we evaluated a number of leukemia cell lines and discovered an aberrant accumulation of cholesteryl ester (CE) in CML, which was found to be a result of BCR-ABL kinase activity...
2017: PloS One
https://www.readbyqxmd.com/read/28716444/thiosemicarbazone-derivatives-thiazolyl-hydrazones-effectively-inhibit-leukemic-tumor-cell-growth-down-regulation-of-ribonucleotide-reductase-activity-and-synergism-with-arabinofuranosylcytosine
#18
Geraldine Graser-Loescher, Agnes Schoenhuber, Caroline Ciglenec, Sabine Eberl, Georg Krupitza, Robert M Mader, Surender S Jadav, Venkatesan Jayaprakash, Monika Fritzer-Szekeres, Thomas Szekeres, Philipp Saiko
Cellular growth inhibition exerted by thiosemicarbazones is mainly attributed to down-regulation of ribonucleotide reductase (RNR) activity, with RNR being responsible for the rate-limiting step of de novo DNA synthesis. In this study, we investigated the antineoplastic effects of three newly synthesized thiosemicarbazone derivatives, thiazolyl hydrazones, in human HL-60 promyelocytic leukemia cells. The cytotoxicity of compounds alone and in combination with arabinofuranosylcytosine (AraC) was determined by growth inhibition assays...
July 14, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28706591/interferon-related-pericarditis-review
#19
Kazuaki Nishio, Tsutomu Arase, Hiroko Tada, Hideaki Tachibana
AIM: To conduct a review of "interferon related pericarditis". METHODS: We searched MEDLINE, EMBASE, Cinahl, and the Cochrane Database from the earliest available date through September 2016. A search strategy using the Medical Subject Headings and text keywords "interferon" and "pericarditis" were used. RESULTS: Nine case reports were eligible for the present study. Six of 8 cases were women and the mean age was 43.8 ± 13.8 years with chronic hepatitis C in 6 cases, malignant melanoma in 2 cases and chronic myelogenous leukemia in 1 case...
June 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28704165/specific-monoclonal-antibody-against-bcr-abl-out-of-frame-alternative-proteins-as-diagnostic-tool-in-chronic-myelogenous-leukemia-patients
#20
Claudia Casnici, Katia Crotta, Gisella Volpe, Cristina Panuzzo, Donatella Lattuada, Giulia Mesiano, Giuseppe Saglio, Ornella Marelli
More recently, alternative splicing of specific genes are investigated for their therapeutic potential. In particular, we reported the existence of BCR-ABL alternative splicing isoforms, in about 80% of Philadelphia-positive patients, which lead to the expression of aberrant proteins. These fusion proteins are characterized by an orphan initial and correct Bcr portion attached to a 112 amino acid sequence, arising from the impairment in the reading frame (reading of ABL exon 4 and 5). We demonstrated that these Abl-out-of-frame (OOF) isoforms could have an immunological role with therapeutic implications...
August 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
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