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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/28924290/a-case-report-of-acute-myelogenous-leukemia-with-turner-syndrome
#2
Nadir Siddiqui, Mirza Faris Ali Baig, Bilal Ahmed Khan
Turner Syndrome was diagnosed in a 45 years old female, known case of Acute Myeloid Leukaemia (AML) with maturation, on Bone Marrow biopsy. She presented with blurred vision, vertigo, exertional dyspnoea and insomnia. She did not show the typical features of Turner syndrome, but her cytogenetis confirmed the diagnosis. Bone marrow biopsy showed diffuse infiltration of blast cells with cellularity around 80-85% and haematopoietic suppression. Karyotype analysis showed: 45 X, -X, t (8; 21) (q22; q22) [According to The International System for Human Cytogenetic Nomenclature (ISCN)]...
September 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/28919910/chloroma-of-the-testis-in-a-patient-with-a-history-of-acute-myeloid-leukemia
#3
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/28918688/role-and-regulation-of-micrornas-targeting-btk-in-acute-myelogenous-leukemia
#4
Lara Rizzotto, Tzung-Huei Lai, Arianna Bottoni, Jennifer A Woyach, Rosa Lapalombella, Clara D Bloomfield, John C Byrd, Deepa Sampath
No abstract text is available yet for this article.
September 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28892146/murine-retrovirally-transduced-bone-marrow-engraftment-models-of-mll-fusion-driven-acute-myelogenous-leukemias-aml
#5
Matthew C Stubbs, Andrei V Krivtsov
MLL-rearranged leukemia represents approximately 5% to 10% of adult acute myelogenous leukemia (AML) and nearly half of all infant/pediatric acute leukemia cases. These leukemias have a poor prognosis, and there are no approved therapeutic options. The rearrangement in the MLL gene leads to aberrant expression of MLL-fusion proteins. These are transforming in murine bone marrow and, in particular, on stem cells and myeloid progenitors derived from bone marrow or fetal liver. The commonality of the MLL fusions is the in-frame fusion of 8 to 11 N-terminal exons of MLL1 (KMT2a) with the C-terminus of a partner fusion gene...
September 11, 2017: Current Protocols in Pharmacology
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
#6
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/28869816/timed-sequential-therapy-for-acute-myelogenous-leukemia-results-of-a-retrospective-study-of-301-patients-and-review-of-the-literature
#7
Kelly J Norsworthy, Amy E DeZern, Hua-Ling Tsai, Wesley A Hand, Ravi Varadhan, Steven D Gore, Ivana Gojo, Keith Pratz, Hetty E Carraway, Margaret Showel, Michael A McDevitt, Douglas Gladstone, Gabriel Ghiaur, Gabrielle Prince, Amy H Seung, Dina Benani, Mark J Levis, Judith E Karp, B Douglas Smith
Timed sequential therapy (TST) aims to improve outcomes in acute myelogenous leukemia (AML) by harnessing drug-induced cell cycle kinetics of AML, where a second drug is timed to coincide with peak leukemia proliferation induced by the first drugs. We analyzed outcomes in 301 newly diagnosed AML patients treated from 2004-2013 with cytarabine, anthracycline, and etoposide TST induction. Median age was 52 (range 20-74) and complete remission rate 68%. With median follow-up 5.8 years, 5-year DFS and overall survival (OS) were 37% (95% CI 31-45%) and 32% (95% CI 27-38%), respectively...
August 30, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28868277/extramedullary-relapse-of-acute-myelogenous-leukemia-presenting-as-a-large-serous-retinal-detachment
#8
Wesley Green, P Kumar Rao, George J Harocopos
BACKGROUND/AIMS: To describe the rare presentation of a large, unilateral, serous retinal detachment as an extramedullary manifestation of acute myelogenous leukemia (AML) recurrence without bone marrow or central nervous system involvement after more than 1 year of follow-up. METHODS: Case report. RESULTS: A teenage patient with AML, previously treated with multiple courses of systemic chemotherapy, radiation, and bone marrow transplant, presented with acute vision loss...
July 2017: Ocular Oncology and Pathology
https://www.readbyqxmd.com/read/28859112/mathematical-modelling-as-a-proof-of-concept-for-mpns-as-a-human-inflammation-model-for-cancer-development
#9
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/28841879/an-integrative-multi-lineage-model-of-variation-in-leukopoiesis-and-acute-myelogenous-leukemia
#10
Joyatee M Sarker, Serena M Pearce, Robert P Nelson, Tamara L Kinzer-Ursem, David M Umulis, Ann E Rundell
BACKGROUND: Acute myelogenous leukemia (AML) progresses uniquely in each patient. However, patients are typically treated with the same types of chemotherapy, despite biological differences that lead to differential responses to treatment. RESULTS: Here we present a multi-lineage multi-compartment model of the hematopoietic system that captures patient-to-patient variation in both the concentration and rates of change of hematopoietic cell populations. By constraining the model against clinical hematopoietic cell recovery data derived from patients who have received induction chemotherapy, we identified trends for parameters that must be met by the model; for example, the mitosis rates and the probability of self-renewal of progenitor cells are inversely related...
August 25, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28834593/characterization-of-purine-rich-element-binding-protein-b-as-a-novel-biomarker-in-acute-myelogenous-leukemia-prognostication
#11
Robert J Kelm, Gurpreet S Lamba, Jamie E Levis, Chris E Holmes
Acute myelogenous leukemia (AML)(1) is an aggressive hematologic cancer characterized by infiltration of proliferative, clonal, abnormally differentiated cells of myeloid lineage in the bone marrow and blood. Malignant cells in AML often exhibit chromosomal and other genetic or epigenetic abnormalities that are useful in prognostic risk assessment. In this study, the relative expression and novel single-stranded DNA (ssDNA) binding function of purine-rich element binding proteins A and B (Purα and Purβ) were systematically evaluated in established leukemia cell lines and in lineage committed myeloid cells isolated from patients diagnosed with a hematologic malignancy...
August 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28830803/acute-promyelocytic-leukemia-in-a-patient-with-chronic-lymphocytic-leukemia-a-case-report
#12
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/28825596/ultrasensitive-mutation-detection-identifies-rare-residual-cells-causing-acute-myelogenous-leukemia-relapse
#13
Brian Parkin, Angelina Londoño-Joshi, Qing Kang, Muneesh Tewari, Andrew D Rhim, Sami N Malek
Acute myelogenous leukemia (AML) frequently relapses after complete remission (CR), necessitating improved detection and phenotypic characterization of treatment-resistant residual disease. In this work, we have optimized droplet digital PCR to broadly measure mutated alleles of recurrently mutated genes in CR marrows of AML patients at levels as low as 0.002% variant allele frequency. Most gene mutations persisted in CR, albeit at highly variable and gene-dependent levels. The majority of AML cases demonstrated residual aberrant oligoclonal hematopoiesis...
August 21, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28822152/-preparation-of-cd123-mono-antibody-modified-tanshinone-%C3%A2-a-loaded-immunoliposome-and-its-in-vitro-evaluation
#14
Yin Wang, Fu-Rong Liu, Hong-Lin Xiang, Hong Qing, Chen Chen, Sheng-Jun Mao, Hui Li
In the study, we developed a novel formulation, CD123 mono-antibody (mAb) modified tanshinone ⅡA loaded immunoliposome (CD123-TanⅡA-ILP) to achieve the targeted drug delivery for leukemia cells. Orthogonal test was used to optimize liposome preparation, and the TanⅡA-loaded PEGylated liposomes (TanⅡA-LP) of S100PC-Chol-(mPEG2000-DSPE)-TanⅡA at 19∶5∶1∶1 molar ratio were prepared by the thin film hydration-probe ultrasonic method. A post-insertion method was applied to prepare CD123-TanⅡA-ILP via thiolated mAb conjugated to the terminal of maleimide-PEG2000-DSPE...
June 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28811020/peanut-agglutinin-and-%C3%AE-cyclodextrin-functionalized-polymer-monolith-microextraction-of-igg-galactosylation-coupled-with-online-ms-detection
#15
Haijiao Zheng, Tenggao Zhu, Xiqian Li, Jiutong Ma, Qiong Jia
A facile online method coupling polymer monolithic microextraction (PMME) with mass spectrometry (MS) was developed for the detection of Immunoglobulin G (IgG) galactosylation glycopeptides. A peanut agglutinin-β-cyclodextrin (PNA-β-CD) functionalized poly(hydroxyethyl methylacrylate-ethyleneglycol dimethacrylate) monolith was designed via a click reaction. Thanking to the specificity of PNA-β-CD for the targets, the material exhibited enhanced enrichment selectivity and extraction efficiency for IgG galactosylation glycopeptides...
August 29, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28808915/cost-effectiveness-of-posaconazole-tablets-for-invasive-fungal-infections-prevention-in-acute-myelogenous-leukemia-or-myelodysplastic-syndrome-patients-in-spain
#16
Rafael Cámara, Irmina Gozalbo, Manuel Jurado, Jaime Sanz, Belén Aragón, Santiago Grau
INTRODUCTION: Posaconazole is superior to fluconazole (FLU) and itraconazole (ITRA) in the prevention of invasive fungal diseases (IFDs) in neutropenic patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). A new tablet formulation of posaconazole with improved pharmacokinetic and pharmacodynamic properties compared to posaconazole oral solution has recently been approved. The objective of this study is to estimate the cost-effectiveness of the newly developed posaconazole tablets versus FLU oral suspension or ITRA oral solution for preventing IFDs in high-risk neutropenic patients with AML or MDS and from the perspective of the Spanish National Health System (NHS)...
August 14, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28802907/the-who-how-and-why-allogeneic-transplant-for-acute-myeloid-leukemia-in-patients-older-than-60years
#17
REVIEW
Sarah A Wall, Steven Devine, Sumithira Vasu
Acute myelogenous leukemia (AML) is primarily a disease of the elderly, and as such, our approach to treatment needs to be tailored to address an aging population. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative treatment for intermediate and high risk AML, and until recently, its use had been limited to a younger population and dependent on availability of a donor. Advances in conditioning regimens, supportive care, and the use of alternative donor sources have greatly expanded access to this therapy...
July 15, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28797620/extended-follow-up-of-patients-treated-with-bendamustine-for-lymphoid-malignancies
#18
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/28782395/myeloablative-busulfan-cytoxan-conditioning-versus-reduced-intensity-fludarabine-melphalan-conditioning-for-allogeneic-hematopoietic-stem-cell-transplant-in-patients-with-acute-myelogenous-leukemia
#19
Vishal Dhere, Scott Edelman, Edmund K Waller, Amelia Langston, Michael Graiser, Erin C Connolly, Jeffrey M Switchenko, Natia Esiashvili, Mohammad K Khan
Fludarabine and melphalan (Flu/Mel) has emerged as a more tolerable chemotherapy-based conditioning regimen compared with busulfan and cyclophosphamide (Bu/Cy) for allogeneic stem cell transplant (allo-hematopoietic stem cell transplantation (HSCT)) patients with acute myelogenous leukemia (AML). We conducted a retrospective review of a single-institution database including patients with AML who received allo-HSCT following conditioning with Mel/Flu or Bu/Cy-based regimens. We performed descriptive statistical analysis to examine patient demographics and clinical outcomes...
August 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28765013/structure-based-design-synthesis-and-in-vitro-antiproliferative-effects-studies-of-novel-dual-brd4-hdac-inhibitors
#20
Mingfeng Shao, Linhong He, Li Zheng, Lingxiao Huang, Yuanyuan Zhou, Taijing Wang, Yong Chen, Mingsheng Shen, Fang Wang, Zhuang Yang, Lijuan Chen
Histone acetylation marks play important roles in controlling gene expressions and are removed by histone deacetylases (HDACs). These marks are read by bromodomain and extra-terminal (BET) proteins, whose targeted inhibitors are under clinical investigation. BET and HDAC inhibitors have been demonstrated to be synergistically killing in Mycinduced murine lymphoma. Herein, we combine the inhibitory activities of BET and HDAC into one molecule through structure-based design method and evaluate its function. The majority of these synthesized compounds showed inhibitory activity against second bromdomains(BRD) of BRD4 and HDAC1...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
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