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Myeloid leukemia

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https://www.readbyqxmd.com/read/28103640/addition-of-cladribine-to-the-standard-induction-treatment-improves-outcomes-in-a-subset-of-elderly-aml-patients-results-of-a-randomized-polish-adult-leukemia-group-palg-phase-ii-trial
#1
Agnieszka Pluta, Tadeusz Robak, Agata Wrzesien-Kus, Bozena Katarzyna Budziszewska, Kazimierz Sulek, Ewa Wawrzyniak, Magdalena Czemerska, Malgorzata Zwolinska, Aleksandra Golos, Aleksandra Holowiecka-Goral, Slawomira Kyrcz-Krzemien, Jaroslaw Piszcz, Janusz Kloczko, Monika Mordak-Domagala, Andrzej Lange, Małgorzata Razny, Krzysztof Madry, Wieslaw Wiktor-Jedrzejczak, Sebastian Grosicki, Aleksandra Butrym, Kazimierz Kuliczkowski, Krzysztof Warzocha, Jerzy Holowiecki, Sebastian Giebel, Richard Szydlo, Agnieszka Wierzbowska
Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients, the present randomized phase II study compares efficacy and toxicity of the DAC (daunorubicin plus cytarabine plus cladribine) regimen with the standard DA (daunorubicin plus cytarabine) regimen in the newly diagnosed AML patients over 60 years of age...
January 19, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28103300/expression-profiling-of-ribosome-biogenesis-factors-reveals-nucleolin-as-a-novel-potential-marker-to-predict-outcome-in-aml-patients
#2
Virginie Marcel, Frédéric Catez, Caroline M Berger, Emeline Perrial, Adriana Plesa, Xavier Thomas, Eve Mattei, Sandrine Hayette, Pierre Saintigny, Philippe Bouvet, Jean-Jacques Diaz, Charles Dumontet
Acute myeloid leukemia (AML) is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28101374/arginine-methylation-of-usp9x-promotes-its-interaction-with-tdrd3-and-its-anti-apoptotic-activities-in-breast-cancer-cells
#3
Nithya Narayanan, Zhihao Wang, Ling Li, Yanzhong Yang
The Tudor domain-containing proteins are characterized by their specific interactions with methylated protein motifs, including methyl-arginines and methyl-lysines. The Tudor domain-containing protein 3 (TDRD3) is one of the major methyl-arginine effector molecules that recognizes methylated arginine residues on histones and the C-terminal domain of RNA polymerase II, and activates transcription. However, majority of the cellular TDRD3 localizes to the cytoplasm and its functions there are still elusive. Here, we have identified ubiquitin-specific protease 9 X-linked (USP9X) as a TDRD3-interacting protein by GST (glutathione S-transferase) pull-down and co-immunoprecipitation...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28100265/allogeneic-stem-cell-transplantation-in-adult-patients-with-acute-myeloid-leukaemia-and-17p-abnormalities-in-first-complete-remission-a-study-from-the-acute-leukemia-working-party-alwp-of-the-european-society-for-blood-and-marrow-transplantation-ebmt
#4
Xavier Poiré, Myriam Labopin, Johan Maertens, Ibrahim Yakoub-Agha, Didier Blaise, Norbert Ifrah, Gérard Socié, Tobias Gedde-Dhal, Nicolaas Schaap, Jan J Cornelissen, Stéphane Vigouroux, Jaime Sanz, Lucienne Michaux, Jordi Esteve, Mohamad Mohty, Arnon Nagler
BACKGROUND: Acute myeloid leukaemia (AML) with 17p abnormalities (abn(17p)) carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT) appears as the only potential curative option. METHODS: To address outcomes after allo-SCT in patients with abn(17p), we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry. RESULTS: One hundred thirty-nine patients with confirmed abn(17p) have been selected...
January 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28099274/can-any-patients-with-chronic-myeloid-leukemia-outside-of-a-clinical-trial-have-their-tyrosine-kinase-inhibitor-discontinued
#5
Michael J Mauro
PURPOSE OF REVIEW: This article critically appraises the state of treatment-free remission as a strategy for patients with chronic myeloid leukemia (CML) in deep remission after therapy with tyrosine kinase inhibitors (TKIs). RECENT FINDINGS: Approximately half of patients with CML defined fairly narrowly by trial criteria - TKI sensitive, in deep molecular remission for a defined period - can successfully maintain protective levels of response after TKI cessation...
January 17, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28099273/making-the-most-of-hypomethylating-agents-in-myelodysplastic-syndrome
#6
Geetika Bhatt, William Blum
PURPOSE OF REVIEW: Hypomethylating agents (HMA) are the preferred therapy for patients with higher risk myelodysplastic syndromes (MDS) and an alternative therapeutic strategy for older patients with acute myeloid leukemia. These agents have improved both survival and quality of life, but results overall remain poor. The purpose of this review is to highlight recent developments in clinical research with HMA in MDS/acute myeloid leukemia over the last year. RECENT FINDINGS: Combination of HMA with B-cell lymphoma-2 inhibitors, hedgehog inhibitors, and a variety of other agents are underway, as are further studies with reformulated HMA that have more favorable pharmacokinetics (including oral bioavailability)...
January 17, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28099272/mixed-phenotype-acute-leukemia-current-challenges-in-diagnosis-and-therapy
#7
Ofir Wolach, Richard M Stone
PURPOSE OF REVIEW: Mixed-phenotype acute leukemia (MPAL) is a rare disease that poses many diagnostic and therapeutic challenges. Patients with MPAL are considered to have poor outcomes. The difficulties in classifying this leukemia, the lack of prospectively collected data concerning therapeutic outcomes, and rare incidence result in much uncertainty as to the best approach for patients with MPAL. RECENT FINDINGS: Recent studies demonstrated that most MPALs are associated with cytogenetic abnormalities; genetic sequencing studies disclose a high frequency of somatic mutations in genes encoding epigenetic regulators, tumor suppressors, and transcription factors...
January 17, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28099271/innovative-strategies-for-adverse-karyotype-acute-myeloid-leukemia
#8
Sabine Blum, Gabriele Greve, Michael Lübbert
PURPOSE OF REVIEW: Adverse karyotype acute myeloid leukemia is a disease particularly of older patients, but also observed in younger patients. Despite all efforts, standard chemotherapy is still generally applied in fit patients, as already for decades, and for nearly all different subtypes of acute myeloid leukemia. Lack of more specifically targeted therapy and the often older age of the patients are complicating treatment, and in the subgroup of patients achieving a complete remission, the strikingly high frequency of relapse is a characteristic of this disease...
January 17, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28098879/cytokines-inducers-and-inhibitors-modulate-mmp-2-and-mmp%C3%A2-9-secretion-by-human-fanconi-anemia-immortalized-fibroblasts
#9
M W Roomi, T Kalinovsky, M Rath, A Niedzwiecki
Acute myeloid leukemia and head and neck squamous cell carcinomas are the major causes of mortality and morbidity in Fanconi anemia (FA) patients. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, have been implicated in tumor invasion and metastasis. Various cytokines, mitogens, growth factors, inducers and inhibitors control MMP activities. We investigated the roles of these in the regulation of MMP-2 and MMP-9 in human immortalized fibroblasts from FA. Human FA immortalized fibroblast cell lines FA-A:PD220 and FA-D2:PD20 were grown in minimum essential medium (MEM) supplemented with 15% fetal bovine serum (FBS) and antibiotics in 24-well tissue culture plates...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098170/targeting-the-pi3k-akt-pathway-via-gli1-inhibition-enhanced-the-drug-sensitivity-of-acute-myeloid-leukemia-cells
#10
Hui Liang, Qi-Li Zheng, Peng Fang, Jian Zhang, Tuo Zhang, Wei Liu, Min Guo, Christopher L Robinson, Shui-Bing Chen, Xiao-Ping Chen, Fang-Ping Chen, Hui Zeng
Combination targeted therapy is commonly used to treat acute myeloid leukemia (AML) patients, particularly in refractory/relapse (RR) population. However, concerns have been raised regarding the safety and patient tolerance of combination chemotherapy. It is critical to choose the appropriate treatment for precision therapy. We performed genome-wide RNA profiling using RNA-Seq to compare the RR group and the complete remission (CR) group (a total of 42 adult AML patients). The Hedgehog (Hh) and PI3K/AKT pathways were upregulated in the RR population, which was further confirmed by western blot and/or qPCR...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097942/cd25-as-an-adverse-prognostic-factor-in-elderly-patients-with-acute-myeloid-leukemia
#11
Shin-Ichiro Fujiwara, Kazuo Muroi, Chihiro Yamamoto, Kaoru Hatano, Kiyoshi Okazuka, Kazuya Sato, Iekuni Oh, Ken Ohmine, Takahiro Suzuki, Keiya Ozawa
OBJECTIVES: CD25 has been reported to be highly expressed in leukemia stem cells and correlated with adverse outcomes in young patients with acute myeloid leukemia (AML). However, the significance of CD25 expression in elderly patients with AML has not yet been investigated. METHODS: We retrospectively analyzed 154 newly diagnosed AML patients aged 60 years or over by flow cytometry. RESULTS: CD25-positive AML was characterized by high white blood cell counts, secondary AML, rare favorable karyotypes, and positivity for CD34 and CD7 antigens, compared with CD25-negative AML...
January 18, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28097863/mitochondria-targeted-protein-ruthenium-photosensitizer-for-efficient-photodynamic-applications
#12
Sabyasachi Chakrabortty, Bikram Keshari Agrawalla, Anne Stumper, Naidu M Vegi, Stephan Fischer, Christian Reichardt, Michael Kögler, Benjamin Dietzek, Michaela Feuring-Buske, Christian Buske, Sven Rau, Tanja Weil
Organelle-targeted photosensitization represents a promising approach in photodynamic therapy where the design of the active photosensitizer (PS) is very crucial. In this work, we developed a macromolecular PS with multiple copies of mitochondria-targeting groups and ruthenium complexes that displays highest phototoxicity towards several cancerous cell lines. In particu-lar, enhanced anti-cancer activity was demonstrated in acute myeloid leukemia cell lines, where significant impairment of proliferation and clonogenicity occurs...
January 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28097792/fish-identifies-a-kat6a-crebbp-fusion-caused-by-a-cryptic-insertional-t-8-16-in-a-case-of-spontaneously-remitting-congenital-acute-myeloid-leukemia-with-a-normal-karyotype
#13
Rachel Barrett, Barbara Morash, David Roback, Chantale Pambrun, Lesley Marfleet, Rhett P Ketterling, Karen Harrison, Jason N Berman
Cytogenetics can inform risk stratification in pediatric acute myeloid leukemia (AML). We describe the first case of a newborn with leukemia cutis found to have AML harboring a cryptic insertional t(8;16)(p11.2;p13.3) with associated KAT6A/CREBBP fusion identified exclusively by fluorescence in situ hybridization (FISH). Expectant management resulted in spontaneous leukemia resolution. The identification of t(8;16)(p11.2;p13.3) may serve as a biomarker for spontaneous remission in congenital AML. FISH for this translocation is warranted in congenital AML with a normal karyotype, and patients with KAT6A/CREBBP fusion should be conservatively managed...
January 18, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28096534/novel-therapeutic-approach-to-improve-hematopoiesis-in-low-risk-mds-by-targeting-mdscs-with-the-fc-engineered-cd33-antibody-bi-836858
#14
E A Eksioglu, X Chen, K-H Heider, B Rueter, K L McGraw, A A Basiorka, M Wei, A Burnette, P Cheng, J Lancet, R Komrokji, J Djeu, A List, S Wei
We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33(+)HLA-DR(-)Lin(-), plays a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it plays an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28096533/impact-of-pretreatment-characteristics-and-salvage-strategy-on-outcome-in-patients-with-relapsed-acute-myeloid-leukemia
#15
R F Schlenk, P Frech, D Weber, P Brossart, H-A Horst, D Kraemer, G Held, M Ringhoffer, A Burchardt, G Kobbe, K Götze, D Nachbaur, T Fischer, M Lübbert, H R Salih, H Salwender, G Wulf, E Koller, M Wattad, W Fiedler, S Kremers, H Kirchen, B Hertenstein, P Paschka, V I Gaidzik, V Teleanu, M Heuser, F Thol, K Döhner, J Krauter, A Ganser, H Döhner
Leukemia accepted article preview online, 18 January 2017. doi:10.1038/leu.2017.22.
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28096272/anti-leukemia-efficacy-and-mechanisms-of-action-of-sl-101-a-novel-anti-cd123-antibody-conjugate-in-acute-myeloid-leukemia
#16
Lina Han, Jeffrey L Jorgensen, Christopher Brooks, Ce Shi, Qi Zhang, Graciela M Nogueras González, Antonio Cavazos, Rongqing Pan, Hong Mu, Sa Wang, Jin Zhou, Gheath Alatrash, Stefan O Ciurea, Michael Rettig, John F DiPersio, Jorge E Cortes, Xuelin Huang, Hagop Kantarjian, Michael Andreeff, Farhad Ravandi-Kashani, Marina Konopleva
PURPOSE: The persistence of leukemia stem cells (LSC)-containing cells after induction therapy may contribute to minimal residual disease (MRD) and relapse in acute myeloid leukemia (AML). We investigated the clinical relevance of CD34+CD123+ LSC-containing cells and anti-leukemia potency of a novel antibody-conjugate SL-101 in targeting CD123+ LSCs. Experimental Methods and Results: In a retrospective study on 86 newly diagnosed AML patients, we demonstrated that a higher proportion of CD34+CD123+ LSC-containing cells in remission was associated with persistent MRD, and predicted shorter relapse-free survival in patients with poor-risk cytogenetics...
January 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28095438/vh1-family-immunoglobulin-repertoire-sequencing-after-allogeneic-hematopoietic-stem-cell-transplantation
#17
Maya K Sethi, Felicitas Thol, Michael Stadler, Michael Heuser, Arnold Ganser, Christian Koenecke, Oliver Pabst
After allogeneic hematopoietic stem cell transplantation (HSCT), recovery of humoral immunity is essential to protect from life-threatening infections. However, monitoring the humoral immune system after transplantation with standard techniques in the clinical routine is imprecise. Here, we performed sequencing of mononuclear bone marrow cells to characterize the VH1-repertoire of switched B cells of healthy volunteers and patients undergoing HSCT. Analysis of healthy bone marrow donors and patients showed virtually no clonally related sequences between individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28095364/acute-myeloid-leukemia-with-myelodysplasia-related-changes-demonstrating-mixed-lineage-phenotype
#18
Babita Kajal, Hong Chang
No abstract text is available yet for this article.
September 22, 2016: Blood
https://www.readbyqxmd.com/read/28095277/long-term-follow-up-of-the-french-stop-imatinib-stim1-study-in-patients-with-chronic-myeloid-leukemia
#19
Gabriel Etienne, Joëlle Guilhot, Delphine Rea, Françoise Rigal-Huguet, Franck Nicolini, Aude Charbonnier, Agnès Guerci-Bresler, Laurence Legros, Bruno Varet, Martine Gardembas, Viviane Dubruille, Michel Tulliez, Marie-Pierre Noel, Jean-Christophe Ianotto, Bruno Villemagne, Martin Carré, François Guilhot, Philippe Rousselot, François-Xavier Mahon
Purpose Imatinib (IM) can safely be discontinued in patients with chronic myeloid leukemia (CML) who have had undetectable minimal residual disease (UMRD) for at least 2 years. We report the final results of the Stop Imatinib (STIM1) study with a long follow-up. Patients and Methods IM was prospectively discontinued in 100 patients with CML with UMRD sustained for at least 2 years. Molecular recurrence (MR) was defined as positivity of BCR-ABL transcript in a quantitative reverse transcriptase polymerase chain reaction assay confirmed by a second analysis point that indicated an increase of one log in relation to the first analysis point at two successive assessments or loss of major molecular response at one point...
January 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28095170/financial-burden-for-patients-with-chronic-myeloid-leukemia-enrolled-in-medicare-part-d-taking-targeted-oral-anticancer-medications
#20
Chan Shen, Bo Zhao, Lei Liu, Ya-Chen Tina Shih
PURPOSE: The number of targeted oral anticancer medications (TOAMs) has grown rapidly in the past decade. The high cost of TOAMs raises concerns about the financial aspect of treatment, especially for patients enrolled in Medicare Part D plans because of the coverage gap. METHODS: We identified patients with chronic myeloid leukemia (CML) who were new TOAM users from the SEER registry data linked with Medicare Part D data, from years 2007 to 2012. We followed these patients throughout the calendar year when they started taking the TOAMs and examined their out-of-pocket (OOP) payments and gross drug costs, taking into account their benefit phase, plan type, and cost share group...
January 17, 2017: Journal of Oncology Practice
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