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Acute myeloid leukaemia

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https://www.readbyqxmd.com/read/28528711/clinical-impact-of-colonization-with-multidrug-resistant-organisms-on-outcome-after-autologous-stem-cell-transplantation-a-retrospective-single-center-study
#1
Sebastian Scheich, Claudia Reinheimer, Christian Brandt, Thomas A Wichelhaus, Michael Hogardt, Volkhard A J Kempf, Uta Brunnberg, Christian Brandts, Olivier Ballo, Ivana von Metzler, Johanna Kessel, Hubert Serve, Björn Steffen
During the last years, a significant increase in infections caused by multidrug-resistant organisms (MDRO) has been noticed, resulting in an increase of mortality in all fields of healthcare. Hematological patients are particularly affected by MDRO infections due to disease- and therapy-related immunosuppression. To determine the impact of colonization with MDRO on overall survival, we retrospectively analyzed data from patients undergoing autologous hematopoietic stem cell transplantation at our institution...
May 18, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28526536/trastuzumab-emtansine-versus-capecitabine-plus-lapatinib-in-patients-with-previously-treated-her2-positive-advanced-breast-cancer-emilia-a-descriptive-analysis-of-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#2
Véronique Diéras, David Miles, Sunil Verma, Mark Pegram, Manfred Welslau, José Baselga, Ian E Krop, Kim Blackwell, Silke Hoersch, Jin Xu, Marjorie Green, Luca Gianni
BACKGROUND: The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. METHODS: EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane...
May 16, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28514443/cancer-progression-by-reprogrammed-bcaa-metabolism-in-myeloid-leukaemia
#3
Ayuna Hattori, Makoto Tsunoda, Takaaki Konuma, Masayuki Kobayashi, Tamas Nagy, John Glushka, Fariba Tayyari, Daniel McSkimming, Natarajan Kannan, Arinobu Tojo, Arthur S Edison, Takahiro Ito
Reprogrammed cellular metabolism is a common characteristic observed in various cancers. However, whether metabolic changes directly regulate cancer development and progression remains poorly understood. Here we show that BCAT1, a cytosolic aminotransferase for branched-chain amino acids (BCAAs), is aberrantly activated and functionally required for chronic myeloid leukaemia (CML) in humans and in mouse models of CML. BCAT1 is upregulated during progression of CML and promotes BCAA production in leukaemia cells by aminating the branched-chain keto acids...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28506782/the-misleading-effect-of-serum-galactomannan-testing-in-high-risk-hematology-patients-receiving-prophylaxis-with-micafungin
#4
A Vena, E Bouza, A Álvarez-Uría, J Gayoso, P Martin-Rabadan, F Cajuste, J Guinea, J Gómez Castellá, R Alonso, P Munoz
OBJECTIVES: To investigate the performance of the routine serum galactomannan (sGM) assay in the diagnosis of invasive aspergillosis (IA) in high-risk hematology patients receiving prophylaxis with micafungin. METHODS: Retrospective study including all hematological patients who received prophylaxis with micafungin during high-risk IA episodes (neutropenic patients after chemotherapy for acute myeloid leukaemia/myelodysplastic syndrome; allogeneic HSCT during early neutropenic phase or graft-versus-host disease requiring high prednisone doses)...
May 12, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28492285/prolonged-intracellular-accumulation-of-light-inducible-nanoparticles-in-leukemia-cells-allows-their-remote-activation
#5
Carlos Boto, Emanuel Quartin, Yijun Cai, Alberto Martín-Lorenzo, María Begoña García Cenador, Sandra Pinto, Rajeev Gupta, Tariq Enver, Isidro Sánchez-García, Dengli Hong, Ricardo Pires das Neves, Lino Ferreira
Leukaemia cells that are resistant to conventional therapies are thought to reside in protective niches. Here, we describe light-inducible polymeric retinoic acid (RA)-containing nanoparticles (NPs) with the capacity to accumulate in the cytoplasm of leukaemia cells for several days and release their RA payloads within a few minutes upon exposure to blue/UV light. Compared to NPs that are not activated by light exposure, these NPs more efficiently reduce the clonogenicity of bone marrow cancer cells from patients with acute myeloid leukaemia (AML) and induce the differentiation of RA-low sensitive leukaemia cells...
May 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28491265/experience-with-ruxolitinib-in-the-treatment-of-polycythaemia-vera
#6
REVIEW
Samah Alimam, Claire Harrison
Polycythaemia vera (PV) is a myeloproliferative neoplasm classically characterized by an erythrocytosis and is associated with a high risk of thromboembolic events, constitutional symptoms burden and risk of transformation to myelofibrosis and acute myeloid leukaemia. Therapy is directed at the haematocrit (HCT) to reduce the risk of thrombotic events and usually comprises low-dose aspirin and phlebotomy to maintain HCT at >45%. Frequently in addition, cytoreductive therapy is indicated in high-risk patients for normalizing haematological parameters to mitigate the occurrence of thromboembolic events...
April 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28490659/runx-transcription-factors-at-the-interface-of-stem-cells-and-cancer
#7
REVIEW
Elitza Deltcheva, Rachael Nimmo
The RUNX1 transcription factor is a critical regulator of normal haematopoiesis and its functional disruption by point mutations, deletions or translocations is a major causative factor leading to leukaemia. In the majority of cases, genetic changes in RUNX1 are linked to loss of function classifying it broadly as a tumour suppressor. Despite this, several recent studies have reported the need for a certain level of active RUNX1 for the maintenance and propagation of acute myeloid leukaemia and acute lymphoblastic leukaemia cells, suggesting an oncosupportive role of RUNX1...
May 10, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28486748/telomere-length-is-an-independent-prognostic-marker-in-mds-but-not-in-de-novo-aml
#8
Jenna Williams, Nicole H Heppel, Bethan Britt-Compton, Julia W Grimstead, Rhiannon E Jones, Sudhir Tauro, David T Bowen, Steven Knapper, Michael Groves, Robert K Hills, Chris Pepper, Duncan M Baird, Chris Fegan
Telomere dysfunction is implicated in the generation of large-scale genomic rearrangements that drive progression to malignancy. In this study we used high-resolution single telomere length analysis (STELA) to examine the potential role of telomere dysfunction in 80 myelodysplastic syndrome (MDS) and 95 de novo acute myeloid leukaemia (AML) patients. Despite the MDS cohort being older, they had significantly longer telomeres than the AML cohort (P < 0·0001) where telomere length was also significantly shorter in younger AML patients (age <60 years) (P = 0·02) and in FLT3 internal tandem duplication-mutated AML patients (P = 0·03)...
May 9, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28476187/early-age-acute-leukemia-revisiting-two-decades-of-the-brazilian-collaborative-study-group
#9
REVIEW
Maria S Pombo-de-Oliveira, Francianne Gomes Andrade
The understanding of leukemogenesis in early-age acute leukemia (EAL) has improved remarkably. Initiating somatic mutations detected in dried neonatal blood spots (DNBS) and in cord blood samples of affected children with leukemia have been proven to be acquired prenatally. However, to date, few epidemiological studies have been carried out exploring EAL that include infants and children 13-24 months of age at the diagnosis. Maternal exposure to transplacental DNA-damaging substances during pregnancy has been suggested to be a risk factor for EAL...
November 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/28474617/diagnostic-prognostic-role-of-micrornas-in-paediatric-acute-myeloid-leukaemia
#10
REVIEW
Sachin Kumar, Sameer Bakhshi
Dysregulation in microRNAs (miRNAs) expression has been observed in distinct acute myeloid leukaemia (AML) subtypes, and their potential as an effective diagnostic and prognostic biomarker is slowly being realized. Certain miRNAs have been found to be associated with various cytogenetic and molecular abnormalities of prognostic significance in AML. Experimental evidences have indicated the potential of modulating miRNA expression as an effective antileukaemic strategy. This has opened a new window for miRNAs-based targeted therapies...
December 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28474100/tumour-genesis-syndrome-severe-hypophosphatemia-and-hypokalemia-may-be-ominous-presenting-findings-in-childhood-acute-myeloid-leukaemia
#11
Winnie Ky Chan, Kai O Chang, Wing Hung Lau
We report a 16-year-old girl who was diagnosed with acute leukaemia and a marked leucocytosis >200 × 10(9)/L. She presented with marked hypophosphatemia, hypokalemia, acute renal failure and acute respiratory failure. These electrolytes disturbances may indicate rapid tumour genesis. These ominous findings required urgent treatment to halt the crises of rapid leukemic cell proliferation. CONCLUSION: Mark hypophosphatemia and hypokalemia may be presenting electrolyte abnormalities in a patient with acute leukaemia, and these may be indicators of aggressive tumour genesis...
May 4, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28470536/flt3-itd-and-its-current-role-in-acute-myeloid-leukaemia
#12
REVIEW
Francisco Alejandro Lagunas-Rangel, Venice Chávez-Valencia
FMS-like tyrosine kinase 3 (FLT3) is a proto-oncogene involved in crucial steps of haematopoiesis such as proliferation, differentiation and survival. In recent years, FLT3 has been an important marker in different haematological malignancies, highlighting in acute myeloid leukaemia, where FLT3 mutations have been associated with the clinical prognosis, treatment and survival of patients. The most common form of FLT3 mutation is an internal tandem duplication (ITD) that promotes ligand-independent auto-phosphorylation and constitutive activation of the receptor...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28466487/risk-of-histological-transformation-and-therapy-related-myelodysplasia-acute-myeloid-leukaemia-in-patients-receiving-radioimmunotherapy-for-follicular-lymphoma
#13
Narendranath Epperla, Anthony Q Pham, Brian L Burnette, Gregory A Wiseman, Thomas M Habermann, William R Macon, Stephen M Ansell, David J Inwards, Ivana N Micallef, Patrick B Johnston, Svetomir N Markovic, Luis F Porrata, Joseph P Colgan, Kay M Ristow, Grzegorz S Nowakowski, Thomas E Witzig
Histological transformation (HT) of follicular lymphoma (FL) to an aggressive lymphoma after chemotherapy remains a key issue. The incidence of HT after radioimmunotherapy (RIT) is unknown. This single institution study analysed the risk of HT in FL after treatment with yttrium-90 ibritumomab tiuxetan in 115 consecutive patients treated during 1987-2012. RIT was administered for progressive FL in 111 (97%) patients and as first-line therapy in the remaining 4. 28% (n = 32) had HT, occurring at a median of 60 months from diagnosis and 20 months after RIT...
May 3, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28452111/epigenetic-dysregulation-of-id4-predicts-disease-progression-and-treatment-outcome-in-myeloid-malignancies
#14
Jing-Dong Zhou, Ting-Juan Zhang, Xi-Xi Li, Ji-Chun Ma, Hong Guo, Xiang-Mei Wen, Wei Zhang, Lei Yang, Yang Yan, Jiang Lin, Jun Qian
Promoter hypermethylation-mediated inactivation of ID4 plays a crucial role in the development of solid tumours. This study aimed to investigate ID4 methylation and its clinical relevance in myeloid malignancies. ID4 hypermethylation was associated with higher IPSS scores, but was not an independent prognostic biomarker affecting overall survival (OS) in myelodysplastic syndrome (MDS). However, ID4 hypermethylation correlated with shorter OS and leukaemia-free survival (LFS) time and acted as an independent risk factor affecting OS in acute myeloid leukaemia (AML)...
April 27, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28443613/corrigendum-intronless-wnt10b-short-variant-underlies-new-recurrent-allele-specific-rearrangement-in-acute-myeloid-leukaemia
#15
Francesca Lazzaroni, Luca Del Giacco, Daniele Biasci, Mauro Turrini, Laura Prosperi, Roberto Brusamolino, Roberto Cairoli, Alessandro Beghini
No abstract text is available yet for this article.
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439893/outcome-after-intensive-reinduction-therapy-and-allogeneic-stem-cell-transplant-in-paediatric-relapsed-acute-myeloid-leukaemia
#16
Lene Karlsson, Erik Forestier, Henrik Hasle, Kirsi Jahnukainen, Ólafur G Jónsson, Birgitte Lausen, Ulrika Norén Nyström, Josefine Palle, Anne Tierens, Bernward Zeller, Jonas Abrahamsson
Given that 30-40% of children with acute myeloid leukaemia (AML) relapse after primary therapy it is important to define prognostic factors and identify optimal therapy. From 1993 to 2012, 543 children from the Nordic countries were treated according to two consecutive protocols: 208 children relapsed. The influence of disease characteristics, first line treatment, relapse therapy and duration of first remission on outcome was analysed. Second complete remission (CR2) was achieved in 146 (70%) patients. Estimated 5-year overall survival (OS5y ) was 39 ± 4% for the whole group and 43 ± 4% for the 190 patients given re-induction therapy, of whom 76% received regimens that included fludarabine, cytarabine (FLA) ± anthracyclines, 18% received Nordic Society for Paediatric Haematology and Oncology (NOPHO) upfront blocks and 5% received other regimens...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28432085/acute-myeloid-leukaemia-in-a-case-with-tatton-brown-rahman-syndrome-the-peculiar-dnmt3a-r882-mutation
#17
Iris H I M Hollink, Ans M W van den Ouweland, H Berna Beverloo, Susan T C J M Arentsen-Peters, C Michel Zwaan, Anja Wagner
BACKGROUND: Recently a novel syndromic form of overgrowth with intellectual disability and distinct facial features was identified caused by constitutional mutations in the epigenetic regulator DNA-methyltransferase 3A (DNMT3A), referred to as Tatton-Brown-Rahman syndrome (TBRS). Somatically acquired mutations in DNMT3A occur in haematological malignancies and are frequently present in acute myeloid leukaemia (AML) affecting in more than 50% the arginine residue at position 882 (R882)...
April 21, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28429049/dysregulation-of-haematopoietic-stem-cell-regulatory-programs-in-acute-myeloid-leukaemia
#18
REVIEW
Silvia Basilico, Berthold Göttgens
Haematopoietic stem cells (HSC) are situated at the apex of the haematopoietic differentiation hierarchy, ensuring the life-long supply of mature haematopoietic cells and forming a reservoir to replenish the haematopoietic system in case of emergency such as acute blood loss. To maintain a balanced production of all mature lineages and at the same time secure a stem cell reservoir, intricate regulatory programs have evolved to control multi-lineage differentiation and self-renewal in haematopoietic stem and progenitor cells (HSPCs)...
April 20, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28428668/prognostic-parameters-of-acute-myeloid-leukaemia-at-presentation
#19
Azra Jahic, Ermina Iljazovic, Samira Hasic, Aida Custovic Arnautovic, Damir Sabitovic, Semir Mesanovic, Haris Sahovic, Vlastimir Simendic
INTRODUCTION: The treatment response and outcome in acute myeloid leukaemia (AML) is heterogeneous. AIM: To analyze the prognostic parameters of AML at presentation. METHODS: The total sample of 44 AML patients was analyzed on the basis of age <55 and ≥55 years, sex, WBC count <50x10/(9)/l and ≥50x10/(9)/l, the Hb concentration <100 g/l and ≥100 g/l, PLT count <100x10/(9)/l and ≥100x10/(9)/l, Karnofsky score <60% and >60%, cytogenetics, CD56 expression, morphological type and types of treatment (standard and reduced induction chemotherapy, high-dose chemotherapy/stem cell transplantation - autologous and HLA matched, related, allogeneic, together and separately)...
February 2017: Medical Archives
https://www.readbyqxmd.com/read/28423659/targeting-hox-pbx-dimers-in-cancer
#20
REVIEW
Richard Morgan, Mohamed El-Tanani, Keith D Hunter, Kevin J Harrington, Hardev S Pandha
The HOX and PBX gene families encode transcription factors that have key roles in establishing the identity of cells and tissues in early development. Over the last 20 years it has become apparent that they are also dysregulated in a wide range of solid and haematological malignancies and have a predominantly pro-oncogenic function. A key mode of transcriptional regulation by HOX and PBX proteins is through their interaction as a heterodimer or larger complex that enhances their binding affinity and specificity for DNA, and there is growing evidence that this interaction is a potential therapeutic target in malignancies that include prostate, breast, renal, ovarian and lung cancer, melanoma, myeloma, and acute myeloid leukaemia...
May 9, 2017: Oncotarget
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