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https://www.readbyqxmd.com/read/28937371/npm1-and-flt3-mutations-in-acute-myeloid-leukemia-with-normal-karyotype-indian-perspective
#1
Sudha Sazawal, Neha Singh, Sonal Jain, Sunita Chhikara, Rekha Chaubey, Jina Bhattacharyya, Kandarpa Kr Saikia, Manoranjan Mahapatra, Renu Saxena
BACKGROUND: FLT3-ITD and NPM1 mutations are considered to be the major determinants of the patient response to therapy and outcome. The primary aim of this study was to establish the correlation between these molecular mutations and the clinico-hematologic parameters as well as the prognostic outcome of the Indian acute myeloid leukemia (AML) patients. MATERIALS AND METHODS: This prospective study involved newly diagnosed nonpromyelocytic AML patients who had undergone complete diagnostic workup, including immunophenotyping, conventional cytogenetics and molecular analysis for NPM1 and FLT3-ITD mutation by reverse transcriptase polymerase chain reaction at presentation...
July 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28935849/acute-myeloid-leukemia-with-mutated-nucleophosmin-1-an-immunogenic-aml-subtype-and-potential-candidate-for-immune-checkpoint-inhibition
#2
Jochen Greiner, Susanne Hofmann, Michael Schmitt, Marlies Götz, Markus Wiesneth, Hubert Schrezenmeier, Donald Bunjes, Hartmut Döhner, Lars Bullinger
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September 21, 2017: Haematologica
https://www.readbyqxmd.com/read/28935132/acute-leukemia-patients-needs-qualitative-findings-and-opportunities-for-early-palliative-care
#3
Nathan A Boucher, Kimberly S Johnson, Thomas W LeBlanc
BACKGROUND AND OBJECTIVE: Patients with acute leukemias likely have needs that palliative care can respond to, yet little is known about specific challenges they face, particularly during active treatment. We examined acute myeloid leukemia (AML) patients' expressed challenges and supports following intensive induction chemotherapy. We aimed to understand opportunities for palliative care interventions in this population. METHODS: A qualitative study of AML patients with high-risk disease at Duke University Hospital, Durham, NC...
September 18, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28934678/establishment-of-cell-line-with-nk-nkt-phenotype-from-myeloid-nk-cell-acute-leukemia
#4
A Darji, N Desai, R Modi, B Khamar, S Rajkumar
Acute Myeloid Leukemia (AML) is the most common malignancy in adults with a 5-year survival rate of 27% of the total affected population. For effective treatment and new drug discovery, cell lines are considered as a very important tool. Here we report an establishment of a continuous human cell line AML-004 with a hypo-diploid chromosome 44 and presence of both NK/NKT phenotypes. The cell line was isolated from the blood sample of myeloid NK cell acute leukemia patients and extensively characterized by flow cytometery, morphology, and cytogentic analysis...
September 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28933777/generation-and-use-of-a-humanized-bone-marrow-ossicle-niche-for-hematopoietic-xenotransplantation-into-mice
#5
Andreas Reinisch, David Cruz Hernandez, Katharina Schallmoser, Ravindra Majeti
Xenotransplantation is frequently used to study normal and malignant hematopoiesis of human cells. However, conventional mouse xenotransplantation models lack essential human-specific bone-marrow (BM)-microenvironment-derived survival, proliferation, and self-renewal signals for engraftment of normal and malignant blood cells. As a consequence, many human leukemias and other hematologic disorders do not robustly engraft in these conventional models. Here, we describe a complete workflow for the generation of humanized ossicles with an accessible BM microenvironment that faithfully recapitulates normal BM niche morphology and function...
October 2017: Nature Protocols
https://www.readbyqxmd.com/read/28933735/clinical-outcomes-and-co-occurring-mutations-in-patients-with-runx1-mutated-acute-myeloid-leukemia
#6
Maliha Khan, Jorge Cortes, Tapan Kadia, Kiran Naqvi, Mark Brandt, Sherry Pierce, Keyur P Patel, Gautam Borthakur, Farhad Ravandi, Marina Konopleva, Steven Kornblau, Hagop Kantarjian, Kapil Bhalla, Courtney D DiNardo
(1) Runt-related transcription factor 1 (RUNX1) mutations in acute myeloid leukemia (AML) are often associated with worse prognosis. We assessed co-occurring mutations, response to therapy, and clinical outcomes in patients with and without mutant RUNX1 (mRUNX1); (2) We analyzed 328 AML patients, including 177 patients younger than 65 years who received intensive chemotherapy and 151 patients >65 years who received hypomethylating agents. RUNX1 and co-existing mutations were identified using next-generation sequencing; (3) RUNX1 mutations were identified in 5...
July 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28931762/emerging-therapies-for-acute-myeloid-leukemia-translating-biology-into-the-clinic
#7
REVIEW
Simon Kavanagh, Tracy Murphy, Arjun Law, Dana Yehudai, Jenny M Ho, Steve Chan, Aaron D Schimmer
Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor outcome; overall survival is approximately 35% at two years and some subgroups have a less than 5% two-year survival. Recently, significant improvements have been made in our understanding of AML biology and genetics. These fundamental discoveries are now being translated into new therapies for this disease. This review will discuss recent advances in AML biology and the emerging treatments that are arising from biological studies...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931515/gemtuzumab-ozogamicin-makes-a-comeback
#8
(no author information available yet)
After being pulled from the market 7 years ago, gemtuzumab ozogamicin has been reapproved by the FDA, this time for adults newly diagnosed with acute myeloid leukemia, as well as patients 2 years of age and older with relapsed/refractory disease. The CD33-targeting antibody-drug conjugate can be given as a single agent or in combination with chemotherapy.
September 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28930710/at-the-intersection-of-faith-culture-and-family-dynamics-a-complex-case-of-refusal-of-treatment-for-childhood-cancer
#9
Amy E Caruso Brown
Refusing treatment for potentially curable childhood cancers engenders much discussion and debate. I present a case in which the competent parents of a young Amish child with acute myeloid leukemia deferred authority for decision making to the child's maternal grandfather, who was vocal in his opposition to treatment. I analyze three related concerns that distinguish this case from other accounts of refused treatment. First, I place deference to grandparents as decision makers in the context of surrogate decision making more generally...
2017: Journal of Clinical Ethics
https://www.readbyqxmd.com/read/28930663/the-trem2-apoe-pathway-drives-the-transcriptional-phenotype-of-dysfunctional-microglia-in-neurodegenerative-diseases
#10
Susanne Krasemann, Charlotte Madore, Ron Cialic, Caroline Baufeld, Narghes Calcagno, Rachid El Fatimy, Lien Beckers, Elaine O'Loughlin, Yang Xu, Zain Fanek, David J Greco, Scott T Smith, George Tweet, Zachary Humulock, Tobias Zrzavy, Patricia Conde-Sanroman, Mar Gacias, Zhiping Weng, Hao Chen, Emily Tjon, Fargol Mazaheri, Kristin Hartmann, Asaf Madi, Jason D Ulrich, Markus Glatzel, Anna Worthmann, Joerg Heeren, Bogdan Budnik, Cynthia Lemere, Tsuneya Ikezu, Frank L Heppner, Vladimir Litvak, David M Holtzman, Hans Lassmann, Howard L Weiner, Jordi Ochando, Christian Haass, Oleg Butovsky
Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. We identified a specific apolipoprotein E (APOE)-dependent molecular signature in microglia from models of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer's disease (AD) and in microglia surrounding neuritic β-amyloid (Aβ)-plaques in the brains of people with AD. The APOE pathway mediated a switch from a homeostatic to a neurodegenerative microglia phenotype after phagocytosis of apoptotic neurons...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28928996/immune-mediated-autonomic-neuropathies-following-allogeneic-stem-cell-transplantation-in-acute-myeloid-leukemia
#11
Abhishek Mangaonkar, Hassan Al Khateeb, Narjust Duma, Erik K St Louis, Andrew McKeon, Mrinal Patnaik, William Hogan, Mark Litzow, Taxiarchis Kourelis
BACKGROUND/AIMS: Autonomic dysfunction (AD) after allogeneic stem cell transplant (SCT) is a rare occurrence and likely immune-mediated in etiology. There is limited literature on this topic and hence, we wish to briefly describe management of two cases at our institution and their outcomes. METHODS: We retrospectively identified two patients with immune-mediated AD after SCT from our database. Immune-mediated AD was defined as AD secondary to an immune-mediated etiology without an alternative cause and responding to immunosuppression...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28928972/screening-of-mutations-in-the-additional-sex-combs-like-1-transcriptional-regulator-tumor-protein-p53-and-kras-proto-oncogene-gtpase-nras-proto-oncogene-gtpase-genes-of-patients-with-myelodysplastic-syndrome
#12
Carolina Leite, Lucas Delmonico, Gilda Alves, Romario José Gomes, Mariana Rodrigues Martino, Aline Rodrigues da Silva, Aline Dos Santos Moreira, Maria Christina Maioli, Luciano Rios Scherrer, Elenice Ferreira Bastos, Roberto Irineu, Maria Helena Ornellas
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis, different degrees of cellular dysplasia, and increased risk of progression to acute myeloid leukemia. International Prognostic Scoring System is the gold standard for MDS classification; however, patients exhibiting different clinical behaviors often coexist in the same group, indicating that the currently available scoring systems are insufficient. The genes that have recently been identified as mutated in MDS, including additional sex combs like 1, transcriptional regulator (ASXL1), tumor protein p53 (TP53), and KRAS proto-oncogene and GTPase (KRAS)/NRAS proto-oncogene, GTPase (NRAS), may contribute to a more comprehensive classification, as well as to the prognosis and progression of the disease...
October 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28928446/tumour-derived-pgd2-and-nkp30-b7h6-engagement-drives-an-immunosuppressive-ilc2-mdsc-axis
#13
Sara Trabanelli, Mathieu F Chevalier, Amaia Martinez-Usatorre, Alejandra Gomez-Cadena, Bérengère Salomé, Mariangela Lecciso, Valentina Salvestrini, Grégory Verdeil, Julien Racle, Cristina Papayannidis, Hideaki Morita, Irene Pizzitola, Camille Grandclément, Perrine Bohner, Elena Bruni, Mukul Girotra, Rani Pallavi, Paolo Falvo, Elisabeth Oppliger Leibundgut, Gabriela M Baerlocher, Carmelo Carlo-Stella, Daniela Taurino, Armando Santoro, Orietta Spinelli, Alessandro Rambaldi, Emanuela Giarin, Giuseppe Basso, Cristina Tresoldi, Fabio Ciceri, David Gfeller, Cezmi A Akdis, Luca Mazzarella, Saverio Minucci, Pier Giuseppe Pelicci, Emanuela Marcenaro, Andrew N J McKenzie, Dominique Vanhecke, George Coukos, Domenico Mavilio, Antonio Curti, Laurent Derré, Camilla Jandus
Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28927796/development-and-evaluation-of-4-pyrrolidin-3-yl-benzonitrile-derivatives-as-inhibitors-of-lysine-specific-demethylase-1
#14
Daniel P Mould, Ulf Bremberg, Allan M Jordan, Matthis Geitmann, Alison E McGonagle, Tim C P Somervaille, Gary J Spencer, Donald J Ogilvie
As part of our ongoing efforts to develop reversible inhibitors of LSD1, we identified a series of 4-(pyrrolidin-3-yl)benzonitrile derivatives that act as successful scaffold-hops of the literature inhibitor GSK-690. The most active compound, 21g, demonstrated a Kd value of 22nM and a biochemical IC50 of 57nM. In addition, this compound displayed improved selectivity over the hERG ion channel compared to GSK-690, and no activity against the related enzymes MAO-A and B. In human THP-1 acute myeloid leukaemia cells, 21g was found to increase the expression of the surrogate cellular biomarker CD86...
August 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28927784/safety-and-efficacy-of-blinatumomab-in-combination-with-a-tyrosine-kinase-inhibitor-for-the-treatment-of-relapsed-philadelphia-chromosome-positive-leukemia
#15
Rita Assi, Hagop Kantarjian, Nicholas J Short, Naval Daver, Koichi Takahashi, Guillermo Garcia-Manero, Courtney DiNardo, Jan Burger, Jorge Cortes, Nitin Jain, William Wierda, Salim Chamoun, Marina Konopleva, Elias Jabbour
OBJECTIVE: The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy...
August 18, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28927163/frequency-and-clinicopathologic-features-of-runx1-mutations-in-patients-with-acute-myeloid-leukemia-not-otherwise-specified
#16
Eunkyoung You, Young-Uk Cho, Seongsoo Jang, Eul-Ju Seo, Jung-Hee Lee, Je-Hwan Lee, Kyoo-Hyung Lee, Kyung-Nam Koh, Ho Joon Im, Jong Jin Seo, Young-Mi Park, Jong-Keuk Lee, Chan-Jeoung Park
Objectives: To evaluate the frequency and clinicopathologic characteristics of RUNX1 mutations, focusing on patients with acute myeloid leukemia not otherwise specified (AML NOS). Methods: Diagnostic samples from 219 patients with AML NOS were analyzed for RUNX1 mutations using standard polymerase chain reaction and direct sequencing. Results: Thirty-one RUNX1 mutations were detected in 33 (15.1%) patients. Mutations clustered in the Runt homology (61...
July 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28927162/myelodysplastic-syndrome-unclassifiable-mds-u-with-1-blasts-is-a-distinct-subgroup-of-mds-u-with-a-poor-prognosis
#17
Elizabeth Margolskee, Robert P Hasserjian, Duane Hassane, Wayne Tam, Susan Mathew, Chi Young Ok, Sa A Wang, Jean Oak, Daniel A Arber, Attilio Orazi
Objectives: Three situations qualify as myelodysplastic syndrome, unclassifiable (MDS-U): (1) refractory cytopenia with dysplasia and 1% blasts in peripheral blood (BL), (2) pancytopenia with unilineage dysplasia (Pan), and (3) persistent cytopenia, less than 5% bone marrow blasts, and less than 10% dysplastic cells and presence of MDS-defining cytogenetic abnormalities (CG). We compared the clinicopathologic features and mutational profiles for these three groups. Methods: MDS-U cases were reviewed at four major academic institutions...
July 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28927153/clinicoradiological-characteristics-management-and-prognosis-of-primary-myeloid-sarcoma-of-the-central-nervous-system-a-report-of-four-cases
#18
Bao Yang, Chenlong Yang, Jingyi Fang, Jun Yang, Yulun Xu
Myeloid sarcoma (MS) is a localized tumor composed of premature precursors of granulocytic cells, which may occur in any organ and most commonly involves the soft tissue and musculoskeletal system. This malignancy may occur in the presence or absence of hematological disorders. Primary MS involving the central nervous system (CNS-MS) is rare, and has only been described in a small number of isolated case reports. The diagnosis of CNS-MS is challenging and strategies for its management are undefined. The present study describes 4 cases of CNS-MS...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927052/synergistic-effects-of-phenylhexyl-isothiocyanate-and-ly294002-on-the-pi3k-akt-signaling-pathway-in-hl-60-cells
#19
Huicong Yang, Yiqun Huang, Yong Zou, Xudong Ma
The aim of the present study was to investigate the synergistic effect of phenylhexyl isothiocyanate (PHI) and LY294002 [an inhibitor of phosphoinositide 3-kinase (PI3K)] on the PI3K/protein kinase B (Akt) signaling pathway, modulating histone acetylation, inhibiting cell viability and inducing apoptosis in HL-60 cells. The inhibition of HL-60 cell viability was monitored using an MTT assay. Cell apoptosis was measured using flow cytometry. Expression of acetylated histone H3 and histone H4, and the Akt signaling pathway proteins phosphorylated Akt (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR) and phosphorylated ribosomal protein S6 kinase (p-p70S6K) was detected using western blotting...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925935/technical-advances-in-the-measurement-of-residual-disease-in-acute-myeloid-leukemia
#20
REVIEW
Gregory W Roloff, Catherine Lai, Christopher S Hourigan, Laura W Dillon
Outcomes for those diagnosed with acute myeloid leukemia (AML) remain poor. It has been widely established that persistent residual leukemic burden, often referred to as measurable or minimal residual disease (MRD), after induction therapy or at the time of hematopoietic stem cell transplant (HSCT) is highly predictive for adverse clinical outcomes and can be used to identify patients likely to experience clinically evident relapse. As a result of inherent genetic and molecular heterogeneity in AML, there is no uniform method or protocol for MRD measurement to encompass all cases...
September 19, 2017: Journal of Clinical Medicine
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