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Myeloid neoplasia

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https://www.readbyqxmd.com/read/28224211/mechanisms-overseeing-myeloid-derived-suppressor-cell-production-in-neoplastic-disease
#1
REVIEW
Colleen S Netherby, Scott I Abrams
Perturbations in myeloid cell differentiation are common in neoplasia, culminating in immature populations known as myeloid-derived suppressor cells (MDSCs). MDSCs favor tumor progression due to their ability to suppress host immunity or promote invasion and metastasis. They are thought to originate from the bone marrow as a result of exposure to stromal- or circulating tumor-derived factors (TDFs). Although great interest has been placed on understanding how MDSCs function, less is known regarding how MDSCs develop at a transcriptional level...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28212262/molecular-cytogenetic-approach-to-characterize-novel-and-cryptic-chromosome-abnormalities-in-childhood-myeloid-malignances-of-fanconi-anemia
#2
Maria L R Borges, Roberto R Capela de Matos, Bethânia D A Silva Amaral, Eliane M Soares-Ventura, Edinalva P Leite, Mariluze O D Silva, Maria T M Nogueira Cornélio, Maria L M Silva, Thomas Liehr, Terezinha D J Marques-Salles
Myeloid malignancies can be either primary or secondary, whether or not a specific cause can be determined. Fanconi anemia (FA), a rare constitutional bone marrow failure, usually presents an increased possibility of clonal evolution, due to the increase in chromosomal instability, TP53 activation, and cell death. The evolution of FA may include aplastic anemia by the progressive failure of the bone marrow and myelod neoplasias, such as acute myeloid leukemia and myelodysplastic syndrome. Chromosome abnormalities, particularly of chromosomes, 1, 3, and 7, during the aplastic phase of the disease are predictive of evolution to acute myeloid leukemia/myelodysplastic syndrome...
March 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28193998/inhibition-of-serotonin-receptor-type-1-in-acute-myeloid-leukemia-impairs-leukemia-stem-cell-functionality-a-promising-novel-therapeutic-target
#3
A Etxabe, M C Lara-Castillo, J M Cornet-Masana, A Banús-Mulet, M Nomdedeu, M A Torrente, M Pratcorona, M Díaz-Beyá, J Esteve, R M Risueño
Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous neoplasia with poor outcome, organized as a hierarchy initiated and maintained by a subpopulation with differentiation and self-renewal capacities called leukemia stem cells (LSCs). Although currently used chemotherapy is capable of initially reducing the tumor burden producing a complete remission, most patients will ultimately relapse and will succumb to their disease. As such, new therapeutic strategies are needed. AML cells differentially expressed serotonin receptors type 1 (HTR1) compared to healthy blood cells and the most primitive hematopoietic fraction; in fact, HTR1B expression on AML patient samples correlated with clinical outcome...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28108287/antitumor-activity-of-a-novel-and-orally-available-inhibitor-of-serine-palmitoyltransferase
#4
Masahiro Yaguchi, Sachio Shibata, Yoshinori Satomi, Megumi Hirayama, Ryutaro Adachi, Yasutomi Asano, Takuto Kojima, Yasuhiro Hirata, Akio Mizutani, Atsushi Kiba, Yoji Sagiya
Metabolic reprogramming is an essential hallmark of neoplasia. Therefore, targeting cancer metabolism, including lipid synthesis, has attracted much interest in recent years. Serine palmitoyltransferase (SPT) plays a key role in the initial and rate-limiting step of de novo sphingolipid biosynthesis, and inhibiting SPT activity prevents the proliferation of certain cancer cells. Here, we identified a novel and orally available SPT inhibitor, compound-2. Compound-2 showed an anti-proliferative effect in several cancer cell models, reducing the levels of the sphingolipids ceramide and sphingomyelin...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28101592/long-term-safety-and-outcome-of-fludarabine-cyclophosphamide-and-mitoxantrone-fcm-regimen-in-previously-untreated-patients-with-advanced-follicular-lymphoma-12%C3%A2-years-follow-up-of-a-phase-2-trial
#5
Laura Magnano, Silvia Montoto, Eva González-Barca, Javier Briones, Juan Manuel Sancho, Ana Muntañola, Antonio Salar, Joan Besalduch, Lourdes Escoda, Carol Moreno, Eva Domingo-Domenech, Cristina Estany, Albert Oriol, Albert Altés, Carmen Pedro, Santiago Gardella, Antoni Asensio, Pilar Vivancos, Alberto Fernández de Sevilla, Josep María Ribera, Dolors Colomer, Elias Campo, Armando López-Guillermo
Fludarabine combinations are very affective in follicular lymphoma (FL) with high rates of complete response and prolonged survival. However, late toxicities could be a concern. The aim of the present study was to analyze the long-term impact on survival, relapse and late toxicities of a trial of treatment with fludarabine, mitoxantrone and cyclophosphamide (FCM regimen) for untreated patients with advanced stage FL. One hundred and twenty patients enrolled in a phase 2 trial of treatment with FCM regimen between 2000 and 2003 were evaluated...
January 18, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28054944/the-role-of-histone-protein-modifications-and-mutations-in-histone-modifiers-in-pediatric-b-cell-progenitor-acute-lymphoblastic-leukemia
#6
REVIEW
Szymon Janczar, Karolina Janczar, Agata Pastorczak, Hani Harb, Adam J W Paige, Beata Zalewska-Szewczyk, Marian Danilewicz, Wojciech Mlynarski
While cancer has been long recognized as a disease of the genome, the importance of epigenetic mechanisms in neoplasia was acknowledged more recently. The most active epigenetic marks are DNA methylation and histone protein modifications and they are involved in basic biological phenomena in every cell. Their role in tumorigenesis is stressed by recent unbiased large-scale studies providing evidence that several epigenetic modifiers are recurrently mutated or frequently dysregulated in multiple cancers. The interest in epigenetic marks is especially due to the fact that they are potentially reversible and thus druggable...
January 3, 2017: Cancers
https://www.readbyqxmd.com/read/27913464/new-challenges-in-evaluating-anemia-in-older-persons-in-the-era-of-molecular-testing
#7
David P Steensma
Anemia is common in older persons, and often remains unexplained despite a thorough clinical history, physical examination, and focused laboratory testing, including marrow aspiration, biopsy, and karyotyping. The advent of molecular genetic testing panels in hematology clinical practice has complicated the evaluation of older patients with unexplained anemia. While the presence of a somatic mutation provides evidence of clonal hematopoiesis and may support a diagnosis of a hematologic neoplasm such as one of the myelodysplastic syndromes (MDS), with rare exceptions, individual mutations are not strongly associated with one specific diagnosis, nor are they by themselves diagnostic of neoplasia...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913051/erg-expression-in-multiple-myeloma-a-potential-diagnostic-pitfall
#8
Juliana Knief, Katharina Reddemann, Jan Gliemroth, Swantje Brede, Tobias Bartscht, Christoph Thorns
INTRODUCTION: ERG expression has been described as a frequent event in prostate cancer indicating poor prognosis and promoting oncogenesis. It has also been demonstrated in Ewing's sarcoma, acute myeloid leukemia and acute T-lymphoblastic leukemia but could not be found in other epithelial tumors, Hodgkin's or Non-Hodgkin's lymphoma. We aimed to analyze ERG expression in multiple myeloma, following an index case of a patient with metastases of unknown origin in the spine strongly expressing ERG, which were thought to be of prostatic origin but turned out to be plasmacytic lesions...
November 3, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27908931/filling-the-tank-keeping-antitumor-t-cells-metabolically-fit-for-the-long-haul
#9
REVIEW
Greg M Delgoffe
Discoveries in tumor immunology and subsequent clinical advances in cancer immunotherapy have revealed that the immune system is not oblivious to tumor progression but heavily interacts with developing neoplasia and malignancy. A major factor preventing immune destruction is the establishment of a highly immunosuppressive tumor microenvironment (TME), which provides architecture to the tumor, supports indirect means of immunosuppression such as the recruitment of tolerogenic cells like regulatory T cells and myeloid-derived suppressor cells (MDSC), and represents a zone of metabolically dearth conditions...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27822101/the-danish-national-chronic-myeloid-neoplasia-registry
#10
REVIEW
Marie Bak, Else Helene Ibfelt, Thomas Stauffer Larsen, Dorthe Rønnov-Jessen, Niels Pallisgaard, Ann Madelung, Lene Udby, Hans Carl Hasselbalch, Ole Weis Bjerrum, Christen Lykkegaard Andersen
AIM: The Danish National Chronic Myeloid Neoplasia Registry (DCMR) is a population-based clinical quality database, introduced to evaluate diagnosis and treatment of patients with chronic myeloid malignancies. The aim is to monitor the clinical quality at the national, regional, and hospital departmental levels and serve as a platform for research. STUDY POPULATION: The DCMR has nationwide coverage and contains information on patients diagnosed at hematology departments from January 2010 onward, including patients with essential thrombocythemia, polycythemia vera, myelofibrosis, unclassifiable myeloproliferative neoplasms, chronic myelomonocytic leukemia, and chronic myeloid leukemia...
2016: Clinical Epidemiology
https://www.readbyqxmd.com/read/27785447/insights-into-the-pathogenesis-of-langerhans-cell-histiocytosis-the-development-of-targeted-therapies
#11
REVIEW
Caroline Hutter, Milen Minkov
More than a century after its first description, Langerhans cell histiocytosis (LCH) still remains an intriguing disease. Considerable progress in understanding its biology has been achieved recently. Description of the V600E BRAF mutation in samples of LCH tissue in 2010 was followed by description of additional mutations, all leading to constitutive ERK activation. Current experimental data suggest that LCH is a myeloid neoplasia with inflammatory properties, yet the exact pathophysiology remains poorly understood...
2016: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/27776290/good-riddance-to-the-term-refractory-anemia-in-myelodysplastic-syndromes
#12
David P Steensma
The term "refractory anemia" was used in 1937 by Cornelius Parker Rhoads to describe patients whose anemia did not improve after treatment with liver extract or iron salts, and this term has been used to denote patients with certain subtypes of myelodysplastic syndromes (MDS) since the 1976 and 1982 French-American-British (FAB) classifications of acute leukemias and MDS. In 2016, the World Health Organization (WHO) proposed elimination of "refractory anemia" in a more general proposal for reclassification of myeloid neoplasia...
December 2016: Leukemia Research
https://www.readbyqxmd.com/read/27738314/loss-of-uhrf2-expression-is-associated-with-human-neoplasia-promoter-hypermethylation-decreased-5-hydroxymethylcytosine-and-high-proliferative-activity
#13
Huarui Lu, Sweta Bhoopatiraju, Hongbo Wang, Nolan P Schmitz, Xiaohong Wang, Matthew J Freeman, Colleen L Forster, Michael R Verneris, Michael A Linden, Timothy C Hallstrom
Ubiquitin-like with PHD and ring finger domains 2 (UHRF2) binds to 5-hydroxymethylcytosine (5hmC), a DNA base involved in tissue development, but it is unknown how their distribution compares with each other in normal and malignant human tissues. We used IHC on human tumor specimens (160 from 19 tumor types) or normal tissue to determine the expression and distribution of UHRF2, Ki-67, and 5hmC. We also examined UHRF2 expression in cord blood progenitors and compared its expression to methylation status in 6 leukemia cell lines and 15 primary human leukemias...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27642531/cardiac-relapse-of-acute-myeloid-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#14
María Facenda-Lorenzo, Ana Sánchez-Quintana, Alejandro Quijada-Fumero, Ana Laynez-Carnicero, Joaquín Breña-Atienza, Francisco J Poncela-Mireles, Juan M Llanos-Gómez, Ana I Cabello-Rodríguez, María Ramos-López
Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse...
2016: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/27639703/biomarkers-of-angiogenesis-as-prognostic-factors-in-myelodysplastic-syndrome-patients-treated-with-hypomethylating-agents
#15
Chan Kyu Kim, Dong Hoon Han, Young Seok Ji, Min Sung Lee, Chang Wook Min, Seong Kyu Park, Se Hyung Kim, Jina Yun, Hyun Jeung Kim, Kyoung Ha Kim, Kyu Taek Lee, Jong Ho Won, Dae Sik Hong, Hee Kyung Kim
Angiogenesis occurs in response to tissue ischemia and wound healing, and contributes to the pathogenesis of a variety of diseases, such as benign and malignant neoplasia. Several studies have measured bone marrow microvessel density (MVD) in MDS patients and acute myeloid leukemia (AML) patients transformed from MDS, and MVD was higher in MDS patients than controls, but was lower than in AML patients. Vascular endothelial growth factor (VEGF) is expressed in bone marrow blast cells, and an autocrine VEGF signaling mechanism has been established in MDS...
September 5, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27467943/high-risk-oncogenic-hpv-genotype-infection-associates-with-increased-immune-activation-and-t-cell-exhaustion-in-art-suppressed-hiv-1-infected-women
#16
Emmanouil Papasavvas, Lea F Surrey, Deborah K Glencross, Livio Azzoni, Jocelin Joseph, Tanvier Omar, Michael D Feldman, Anna-Lise Williamson, Maureen Siminya, Avril Swarts, Xiangfan Yin, Qin Liu, Cynthia Firnhaber, Luis J Montaner
Persistence of human papillomavirus (HPV) and cervical disease in the context of HIV co-infection can be influenced by introduction of antiretroviral therapy (ART) and sustained immune activation despite ART. We conducted a cross-sectional study in order to evaluate immune activation/exhaustion in ART-suppressed HIV(+) women with or without high-risk (HR) HPV-related cervical intraepithelial neoplasia (CIN). 55 South African women were recruited in three groups: HR (-) (n = 16) and HR (+) (n = 15) HPV with negative cervical histopathology, and HR (+) HPV with CIN grade 1/2/3 (n = 24)...
May 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27459623/-transformation-of-secondary-myelodysplastic-syndrome-to-atypical-chronic-myeloid-leukemia-in-a-female-patient-with-acute-myeloid-leukemia
#17
S V Gritsaev, I I Kostroma, I M Zapreeva, A V Shmidt, S A Tiranova, V A Balashova, I S Martynkevich, Zh V Chubukina, N Yu Semenova, A V Chechetkin
Secondary myeloid neoplasia may be a complication of intensive cytostatic therapy. The most common types of secondary neoplasias are acute myeloid leukemia and myelodysplastic syndrome. The development of secondary atypical chronic myeloid leukemia (aCML) is an extremely rare phenomenon. The paper describes transformation of secondary myelodysplastic syndrome to aCML 6 months after its diagnosis. The development of aCML was accompanied by additional chromosomal aberration as monosomy of chromosome 17. No mutations in the JAK2, MPL, and CalR genes were detected...
2016: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/27454293/rela-a-tale-of-a-stitch-in-time
#18
Murray Korc
Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer in which NF-κB pathways promote biological aggressiveness. In this issue of the JCI, Lesina et al. investigated the role of RelA, the p65 partner of p50 that together form the most common NF-κB complex, in the early stages of pancreatic malignant transformation and in established PDAC. By deleting Rela in the context of an oncogenic Kras-driven autochthonous model of PDAC, the authors demonstrated that RelA is a mediator of oncogene-induced senescence (OIS) and the senescence-associated secretory phenotype (SASP) that attenuates acinar-to-ductal metaplasia, pancreatic intraepithelial neoplasia (PanIN) formation, and PanIN progression to PDAC...
August 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27382093/braf-mutation-correlates-with-high-risk-langerhans-cell-histiocytosis-and-increased-resistance-to-first-line-therapy
#19
Sébastien Héritier, Jean-François Emile, Mohamed-Aziz Barkaoui, Caroline Thomas, Sylvie Fraitag, Sabah Boudjemaa, Florence Renaud, Anne Moreau, Michel Peuchmaur, Catherine Chassagne-Clément, Frédérique Dijoud, Valérie Rigau, Despina Moshous, Anne Lambilliotte, Françoise Mazingue, Kamila Kebaili, Jean Miron, Eric Jeziorski, Geneviève Plat, Nathalie Aladjidi, Alina Ferster, Hélène Pacquement, Claire Galambrun, Laurence Brugières, Guy Leverger, Ludovic Mansuy, Catherine Paillard, Anne Deville, Corinne Armari-Alla, Anne Lutun, Marion Gillibert-Yvert, Jean-Louis Stephan, Fleur Cohen-Aubart, Julien Haroche, Isabelle Pellier, Frédéric Millot, Brigitte Lescoeur, Virginie Gandemer, Christine Bodemer, Roger Lacave, Zofia Hélias-Rodzewicz, Valérie Taly, Frédéric Geissmann, Jean Donadieu
PURPOSE: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAF(V600E) mutation occurs frequently, but clinical significance remains to be determined. PATIENTS AND METHODS: BRAF(V600E) mutation was investigated in a French LCH cohort. We analyzed associations between mutation status and clinical presentation, extent of disease, reactivation rate, response to therapy, and long-term permanent sequelae...
September 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27379866/relevance-of-interferon-regulatory-factor-8-expression-in-myeloid-tumor-interactions
#20
Scott I Abrams, Colleen S Netherby, Danielle Y F Twum, Michelle N Messmer
Perturbations in myelopoiesis are a common feature in solid tumor biology, reflecting the central premise that cancer is not only a localized affliction but also a systemic disease. Because the myeloid compartment is essential for the induction of adaptive immunity, these alterations in myeloid development contribute to the failure of the host to effectively manage tumor progression. These "dysfunctional" myeloid cells have been coined myeloid-derived suppressor cells (MDSCs). Interestingly, such cells not only arise in neoplasia but also are associated with many other inflammatory or pathologic conditions...
July 2016: Journal of Interferon & Cytokine Research
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