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Acute myeloid leukaemia

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https://www.readbyqxmd.com/read/28928446/tumour-derived-pgd2-and-nkp30-b7h6-engagement-drives-an-immunosuppressive-ilc2-mdsc-axis
#1
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
#2
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/28924290/a-case-report-of-acute-myelogenous-leukemia-with-turner-syndrome
#3
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/28906004/acute-myeloid-leukaemia-fab-aml-m4eo-with-cryptic-insertion-of-cbfb-resulting-in-cbfb-myh11-fusion
#4
Nathalie Douet-Guilbert, Aurelie Chauveau, Nadia Gueganic, Gaëlle Guillerm, Corine Tous, Marie-Josee Le Bris, Audrey Basinko, Frederic Morel, Valerie Ugo, Marc De Braekeleer
Inv(16)(p13q22) and t(16;16)(p13;q22) are cytogenetic hallmarks of acute myelomonoblastic leukaemia, most of them associated with abnormal bone marrow eosinophils [acute myeloid leukaemia French-American-British classification M4 with eosinophilia (FAB AML-M4Eo)] and a relatively favourable clinical course. They generate a 5'CBFB-3'MYH11 fusion gene. However, in a few cases, although RT-PCR identified a CBFB-MYH11 transcript, normal karyotype and/or fluorescent in situ hybridization (FISH) analyses using commercially available probes are found...
September 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28901021/optimisation-of-chemotherapy-and-radiotherapy-for-untreated-hodgkin-lymphoma-patients-with-respect-to-second-malignant-neoplasms-overall-and-progression-free-survival-individual-participant-data-analysis
#5
REVIEW
Jeremy Franklin, Dennis A Eichenauer, Ingrid Becker, Ina Monsef, Andreas Engert
BACKGROUND: Efficacy and the risk of severe late effects have to be well-balanced in treatment of Hodgkin lymphoma (HL). Late adverse effects include secondary malignancies which often have a poor prognosis. To synthesise evidence on the risk of secondary malignancies after current treatment approaches comprising chemotherapy and/or radiotherapy, we performed a meta-analysis based on individual patient data (IPD) from patients treated for newly diagnosed HL. OBJECTIVES: We investigated several questions concerning possible changes in the risk of secondary malignancies when modifying chemotherapy or radiotherapy (omission of radiotherapy, reduction of the radiation field, reduction of the radiation dose, use of fewer chemotherapy cycles, intensification of chemotherapy)...
September 13, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28898234/circulating-cytokines-and-small-molecules-follow-distinct-expression-patterns-in-acute-myeloid-leukaemia
#6
Mirazul Islam, Elsa Haniffah Mohamed, Ezalia Esa, Nor Rizan Kamaluddin, Shamsul Mohd Zain, Yuslina Mat Yusoff, Yassen Assenov, Zahurin Mohamed, Zubaidah Zakaria
BACKGROUND: Although aberrant expression of cytokines and small molecules (analytes) is well documented in acute myeloid leukaemia (AML), their co-expression patterns are not yet identified. In addition, plasma baselines for some analytes that are biomarkers for other cancers have not been previously reported in AML. METHODS: We used multiplex array technology to simultaneously detect and quantify 32 plasma analyte (22 reported analytes and 10 novel analytes) levels in 38 patients...
September 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28894287/prognostic-significance-of-high-gfi1-expression-in-aml-of-normal-karyotype-and-its-association-with-a-flt3-itd-signature
#7
Giacomo Volpe, David S Walton, David E Grainger, Carl Ward, Pierre Cauchy, Daniel Blakemore, Daniel J L Coleman, Peter N Cockerill, Paloma Garcia, Jon Frampton
Growth Factor Independence 1 (GFI1) is a transcriptional repressor that plays a critical role during both myeloid and lymphoid haematopoietic lineage commitment. Several studies have demonstrated the involvement of GFI1 in haematological malignancies and have suggested that low expression of GFI1 is a negative indicator of disease progression for both myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). In this study, we have stratified AML patients into those defined as having a normal karyotype (CN-AML)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28892915/myeloid-sarcoma-presenting-as-nasal-and-orbital-mass-an-initial-manifestation-of-an-acute-myeloid-leukaemia
#8
Amita Jain Gupta, Shramana Mandal, Richa Gupta, Nita Khurana, Achal Gulati
Myeloid sarcoma is an extramedullary manifestation of Acute Myeloid Leukaemia and sometimes is the only indicator of the disease. The incidence varies between 3-9.1% of acute leukaemia cases. The blast infiltration is seen most commonly in skin, lymph node, gastrointestinal tract, bone, soft tissue though can involve any body site usually as a solitary lesion and is rarely seen in nasal cavity. We present two cases of myeloid sarcoma presenting as a nasal mass in a six year old girl and other as orbital mass in 32-year-old as an initial manifestation of acute myeloid leukaemia...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28892629/development-of-4-cyanophenyl-glycine-derivatives-as-reversible-inhibitors-of-lysine-specific-demethylase-1
#9
Daniel P Mould, Cristina Alli, Ulf Bremberg, Sharon Cartic, Allan M Jordan, Matthis Geitmann, Alba Maiques-Diaz, Alison E McGonagle, Tim C P Somervaille, Gary J Spencer, Fabrice Turlais, Donald Ogilvie
Inhibition of lysine specific demethylase 1 (LSD1) has been shown to induce the differentiation of leukemia stem cells in acute myeloid leukemia (AML). Irreversible inhibitors developed from the nonspecific inhibitor tranylcypromine have entered clinical trials; however, the development of effective reversible inhibitors has proved more challenging. Herein, we describe our efforts to identify reversible inhibitors of LSD1 from a high throughput screen and subsequent in silico modeling approaches. From a single hit (12) validated by biochemical and biophysical assays, we describe our efforts to develop acyclic scaffold-hops from GSK-690 (1)...
September 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28879716/concomitant-occurrence-of-blastic-plasmacytoid-dendritic-cell-neoplasm-and-acute-myeloid-leukaemia-after-lenalidomide-treatment-for
#10
Nicola S Fracchiolla, Alessanda Iurlo, Valeria Ferla, Bruno Fattizzo, Alessandra Freyrie, Gianluigi Reda, Agostino Cortelezzi
BACKGROUND: Myelodysplastic syndromes with chromosome 5 long arm deletion (5q-mds) may benefit from lenalidomide treatment. However, unresponsive patients have a high risk for clonal evolution and progression to acute myeloid leukemia. Case: We describe a 5q-patient treated with lenalidomide, who concomitantly developed acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm, a rare and highly aggressive lymphoma. CONCLUSIONS: Evolution of 5q- syndrome to acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm may have occurred through various mechanisms, including persistence of neoplastic lenalidomide-resistant stem cells and selection of a more aggressive clone via lenalidomide augmentation of the ARPC1B gene, or because of lenalidomide stimulation on dendritic cells...
September 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28879540/enasidenib-first-global-approval
#11
Esther S Kim
Enasidenib (Idhifa(®)) is an oral isocitrate dehydrogenase-2 (IDH2) inhibitor developed by Celgene Corporation under a global, exclusive license from Agios Pharmaceuticals. Enasidenib has been approved in the USA for the treatment of adults with relapsed or refractory acute myeloid leukaemia (AML) and an IDH2 mutation as detected by an FDA-approved test. It is at various stages of development in other countries for AML, myelodysplastic syndromes and solid tumours. This article summarizes the milestones in the development of enasidenib leading to this first global approval in the USA for the treatment of adults with relapsed or refractory IDH2-mutated AML...
September 6, 2017: Drugs
https://www.readbyqxmd.com/read/28868017/natural-killer-cell-lymphoblastic-leukaemia-lymphoma-case-report-and-review-of-the-recent-literature
#12
Qanita Sedick, Sultan Alotaibi, Saeed Alshieban, Khalid Ben Naheet, Ghaleb Elyamany
Natural killer (NK) cell lymphoblastic leukaemia/lymphoma is a rare haemopoietic tumour currently defined in the 2008 WHO classification under the category of acute leukaemias of ambiguous lineage. A diagnosis of this type of leukaemia is considered in cases expressing CD56 along with immature T-cell-associated markers such as CD2 and CD7 with absence of B-cell and myeloid markers; in addition, blastic plasmacytoid dendritic cell leukaemia should be excluded. Prior to 2008, these precursor NK cell lymphoblastic leukaemias/lymphomas were categorized as myeloid/NK cell acute leukaemia with a phenotype identical to acute myeloid leukaemia with minimal differentiation...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28866704/unexpected-infant-death-secondary-to-a-pulmonary-infiltration-due-to-acute-myelocytic-leukaemia
#13
M Ben Khelil, Y Chkirbene, M Mlika, S Haouet, M Hamdoun
Acute myeloid leukaemia (AML) often presents with non-specific symptoms such as fatigue, anaemia or infection. Pulmonary involvement is uncommon in AML during the course of the disease and is usually caused by infection, haemorrhage, leukaemic pulmonary infiltrates and leukostasis. Lung localization of AML is very uncommon and potentially life threatening if not diagnosed and treated rapidly. The authors describe the sudden death of an asymptomatic five-month-infant because of a misdiagnosed lung localization of AML...
August 2017: Malaysian Journal of Pathology
https://www.readbyqxmd.com/read/28866328/splicing-dysfunction-and-disease-the-case-of-granulopoiesis
#14
REVIEW
Maria-Cristina Keightley, Graham J Lieschke
Splicing is a ubiquitous process in eukaryotic cells, long recognised as contributing to diversity of the transcriptome. More specifically, splicing fine-tunes the transcriptome output for highly individual outcomes at different stages of cell development, in specific timeframes, which when perturbed result in significant human diseases. Granulopoiesis provides a particularly well studied example of how splicing can be a highly flexible but tightly regulated process. Focusing on the specific case of granulopoiesis, this review surveys the contribution of cis-splicing variations in individual genes and the trans-regulation of global splicing outcomes during the normal development of neutrophils...
August 30, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28863357/dual-inhibition-of-mnk2-and-flt3-for-potential-treatment-of-acute-myeloid-leukaemia
#15
Sarah Diab, Ahmad M Abdelaziz, Peng Li, Theodosia Teo, Sunita K C Basnet, Ben Noll, Muhammed H Rahaman, Jingfeng Lu, Jinqiang Hou, Mingfeng Yu, Bich T Le, Hugo Albrecht, Robert W Milne, Shudong Wang
The discovery of novel anti-AML therapeutic agents is urgently needed, but the complex heterogeneity of the disease has so far hampered the development of a curative treatment. FLT3 inhibitors have shown therapeutic potential in clinical trials; but a monotherapy regimen has been associated with resistance mediated by the activation of parallel signalling circuitry, including MAPK and mTOR. Therefore, inhibiting a nexus of the two signalling pathways along with inhibition of FLT3 might be advantageous. Herein, we propose that a dual inhibition of FLT3 and Mnk would provide a better clinical option for AML patients compared to targeting FLT3 alone...
August 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28861128/pyrosequencing-quantified-methylation-level-of-mir-124-predicts-shorter-survival-for-patients-with-myelodysplastic-syndrome
#16
Hong Wang, Tong-Tong Zhang, Song Jin, Hong Liu, Xiang Zhang, Chang-Geng Ruan, De-Pei Wu, Yue Han, Xiao-Qin Wang
BACKGROUND: Aberrant CpG island methylation has been increasingly recognized as a common event in myelodysplastic syndrome (MDS). To date, most of the previous studies of miR-124 in MDS have focused on epigenetic changes and little is known about the underlying mechanism through which miR-124 regulates CDK6 expression. RESULTS: In the present study, we employed pyrosequencing analysis to quantify the methylation levels of upstream regions of the miR-124 genes (miR-124-1, miR-124-2 and miR-124-3) in 56 primary MDS patients...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28844818/guadecitabine-a-new-therapeutic-option-for-acute-myeloid-leukaemia
#17
Felicetto Ferrara
No abstract text is available yet for this article.
August 24, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28844816/guadecitabine-sgi-110-in-treatment-naive-patients-with-acute-myeloid-leukaemia-phase-2-results-from-a-multicentre-randomised-phase-1-2-trial
#18
Hagop M Kantarjian, Gail J Roboz, Patricia L Kropf, Karen W L Yee, Casey L O'Connell, Raoul Tibes, Katherine J Walsh, Nikolai A Podoltsev, Elizabeth A Griffiths, Elias Jabbour, Guillermo Garcia-Manero, David Rizzieri, Wendy Stock, Michael R Savona, Todd L Rosenblat, Jesus G Berdeja, Farhad Ravandi, Edwin P Rock, Yong Hao, Mohammad Azab, Jean-Pierre J Issa
BACKGROUND: The hypomethylating drugs azacitidine and decitabine have shown efficacy in myelodysplastic syndromes and acute myeloid leukaemia, but complete tumour responses are infrequent and of short duration, possibly because of the short half-lives and suboptimal bone marrow exposure of the drugs. Guadecitabine, a next-generation hypomethylating drug, has a longer half-life and exposure than its active metabolite decitabine. A phase 1 study established 60 mg/m(2) guadecitabine for 5 days as an effective treatment schedule...
August 24, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28835214/ageing-exposure-to-pollution-and-interactions-between-climate-change-and-local-seasons-as-oxidant-conditions-predicting-incident-hematologic-malignancy-at-kinshasa-university-clinics-democratic-republic-of-congo-drc
#19
Mireille Solange Nganga Nkanga, Benjamin Longo-Mbenza, Oladele Vincent Adeniyi, Jacques Bikaula Ngwidiwo, Antoine Lufimbo Katawandja, Paul Roger Beia Kazadi, Alain Nganga Nzonzila
BACKGROUND: The global burden of hematologic malignancy (HM) is rapidly rising with aging, exposure to polluted environments, and global and local climate variability all being well-established conditions of oxidative stress. However, there is currently no information on the extent and predictors of HM at Kinshasa University Clinics (KUC), DR Congo (DRC). This study evaluated the impact of bio-clinical factors, exposure to polluted environments, and interactions between global climate changes (EL Nino and La Nina) and local climate (dry and rainy seasons) on the incidence of HM...
August 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28821995/expression-of-the-pol-gene-of-human-endogenous-retroviruses-herv-k-and-w-in-leukemia-patients
#20
Massimiliano Bergallo, Paola Montanari, Katia Mareschi, Chiara Merlino, Massimo Berger, Ilaria Bini, Valentina Daprà, Ilaria Galliano, Franca Fagioli
The human endogenous retroviruses (HERVs) are a family of endogenous retroviruses that integrated into the germ cell DNA of primates over 30 million years ago. HERV expression seems impaired in several diseases, ranging from autoimmune to neoplastic disorders. The purpose of this study was to evaluate the overall endogenous retroviral transcription profile in bone marrow (BM) samples. A total of 30 paediatric high-risk leukaemia patients (lymphoid and myeloid malignancies) were tested for HERVs virus gene expression...
August 18, 2017: Archives of Virology
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