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Myeloid neoplasia

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...
October 12, 2016: Oncotarget
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
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
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
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
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
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
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
Adèle De Arcangelis, Hussein Hamade, Fabien Alpy, Sylvain Normand, Emilie Bruyère, Olivier Lefebvre, Agnès Méchine-Neuville, Stéphanie Siebert, Véronique Pfister, Patricia Lepage, Patrice Laquerriere, Doulaye Dembele, Anne Delanoye-Crespin, Sophie Rodius, Sylvie Robine, Michèle Kedinger, Isabelle Van Seuningen, Patricia Simon-Assmann, Mathias Chamaillard, Michel Labouesse, Elisabeth Georges-Labouesse
OBJECTIVE: Epidemiological and clinical data indicate that patients suffering from IBD with long-standing colitis display a higher risk to develop colorectal high-grade dysplasia. Whereas carcinoma invasion and metastasis rely on basement membrane (BM) disruption, experimental evidence is lacking regarding the potential contribution of epithelial cell/BM anchorage on inflammation onset and subsequent neoplastic transformation of inflammatory lesions. Herein, we analyse the role of the α6β4 integrin receptor found in hemidesmosomes that attach intestinal epithelial cells (IECs) to the laminin-containing BM...
July 1, 2016: Gut
Antonella Rigo, Fabrizio Vinante
The sesquiterpene α-bisabolol (α-BSB) has been shown to be an effective cytotoxic agent for a variety of human cancer cells in culture and animal models. However, much of its intracellular action remains elusive. We evaluated the cytotoxic action of α-BSB against CML-T1, Jurkat and HeLa cell lines, as preclinical models for myeloid, lymphoid and epithelial neoplasias. The approach included single cell analysis (flow cytometry, immunocytology) combined with cytotoxicity and proliferation assays to characterize organelle damage, autophagy, cytostatic effect, and apoptosis...
August 2016: Apoptosis: An International Journal on Programmed Cell Death
Julien Haroche, Matthias Papo, Fleur Cohen-Aubart, Frédéric Charlotte, Philippe Maksud, Philippe A Grenier, Philippe Cluzel, Alexis Mathian, Jean-François Emile, Zahir Amoura
In a compatible clinico-radiological setting, the diagnosis of Erdheim-Chester disease (ECD) involves the analysis of histiocytes in tissue biopsies: they are typically foamy and CD68+ CD1a, whereas in Langerhans cell histiocytosis (LCH) they are CD68+ CD1a+. Overlap forms of histiocytoses are frequent. Technetium bone scintigraphy showing nearly constant tracer uptake by the long bones is highly suggestive of ECD and a 'hairy kidney' appearance on abdominal CT scan is observed in more than half ECD cases. CNS involvement is a strong prognostic factor and an independent predictor of death in cases of ECD...
May 24, 2016: La Presse Médicale
Leigh Ellis, ShengYu Ku, Qiuhui Li, Gissou Azabdaftari, Joseph Seliski, Brian Olson, Colleen S Netherby, Dean G Tang, Scott I Abrams, David W Goodrich, Roberto Pili
INTRODUCTION: Transgenic mouse modeling is a favorable tool to reflect human prostate tumorigenesis and interactions between prostate cancer and the microenvironment. The use of GEMMs and derived cell lines represent powerful tools to study prostate cancer initiation and progression with an associated tumor microenvironment. Notably, such models provide the capacity for rapid preclinical therapy studies including immune therapies for prostate cancer treatment. METHODS: Backcrossing FVB Hi-MYC mice with C57BL/6N mice, we established a Hi-MYC transgenic mouse model on a C57BL/6 background (B6MYC)...
September 2016: Prostate
Michael Heuser, Felicitas Thol, Arnold Ganser
BACKGROUND: Patients with cytopenia are increasingly undergoing molecular genetic tests of periperal blood or bone marrow for diagnostic purposes. These tests can detect genetic mutations that do not have any morphological correlate in hematologic neoplasia such as myelo - dysplastic syndrome (MDS). A new entity was recently defined to lessen the risk of incorrect diagnoses of MDS. This new entity is a potential precursor of myeloid diseases, analogously to monoclonal gammopathy of undetermined significance as a potential precursor of multiple myeloma...
May 6, 2016: Deutsches Ärzteblatt International
Silvana Morello, Aldo Pinto, Corrado Blandizzi, Luca Antonioli
Adenosine, deriving from ATP released by dying cancer cells and then degradated in the tumor environment by CD39/CD73 enzyme axis, is linked to the generation of an immunosuppressed niche favoring the onset of neoplasia. The effects of adenosine are mediated by four adenosine receptors, named A1, A2A, A2B and A3 that are widely expressed on several immune cell populations. A critical role of this nucleoside is emerging in the modulation of myeloid cell subsets accumulation and functions into tumor microenvironment, providing new insights that might be useful for the development of novel therapeutic approaches aimed to undermine the immune privileged sites where cancer cells grow and proliferate...
March 2016: Oncoimmunology
Adriana Olar, Razvan Lapadat, Christian J Davidson, Thor D Stein, Sonika Dahiya, Arie Perry, Gabriela Gheorghe
Myeloid sarcoma (MS) is an extramedullary malignancy of myeloid origin. It can occur in any organ. Common sites are skin, bone, lymph nodes, and soft tissue. Central nervous system (CNS) involvement is very uncommon. We report 12 new pathology-confirmed cases of CNS MS with literature review. Median age was 42.5 years (range: 0 - 84 years). Bone marrow involvement by hematologic neoplasia was co-incidental (n = 8) or occurred 8 - 51 months prior to CNS MS (n = 3). Abnormal radiological findings detected in all patients, included hemorrhagic (n = 5) or enhancing (n = 2) lesions, with multiple ring-enhancing dura-based masses in 1 patient...
September 2016: Clinical Neuropathology
Jean E Goasguen, John M Bennett, Barbara J Bain, Richard D Brunning, Maria-Teresa Vallespí, Masao Tomonaga, Gina Zini, Alain Renault
Evaluation of megakaryocyte morphology is difficult but can be essential for the diagnosis of myelodysplastic syndromes (MDS) and other myeloid neoplasms. We agreed upon descriptions and provided images of megakaryoblasts and of normal and dysplastic megakaryocytes, which were used as a basis for assessing the concordance of expert morphologists in their recognition. We showed a high rate of concordance for the recognition of micromegakaryocytes and confirmed their strong association with hematologic neoplasia, including MDS...
June 2016: Leukemia Research
L Dang, K Yen, E C Attar
Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes, converting isocitrate to α-ketoglutarate (αKG).IDH1 and IDH2 mutations have been identified in multiple tumor types, including gliomas and myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Here we provide an overview of the function of normal and mutated IDH, discuss the role of IDH mutations in tumorigenesis and progression and review the key clinical considerations when treating IDH-mutated tumors based on emerging clinical data from mutant IDH1/2 inhibitor trials...
April 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Josep Maria Cornet-Masana, Daniel Moreno-Martínez, María Carmen Lara-Castillo, Meritxell Nomdedeu, Amaia Etxabe, Niccolò Tesi, Marta Pratcorona, Jordi Esteve, Ruth M Risueño
Acute myeloid leukemia (AML) is an hematologic neoplasia characterized by the accumulation of transformed immature myeloid cells in bone marrow. Although the response rate to induction therapy is high, survival rate 5-year after diagnosis is still low, highlighting the necessity of new novel agents. To identify agents with the capability to abolish the self-renewal capacity of AML blasts, an in silico screening was performed to search for small molecules that induce terminal differentiation. Emetine, a hit compound, was validated for its anti-leukemic effect in vitro, ex vivo and in vivo...
April 26, 2016: Oncotarget
Ana Cristina Gonçalves, Raquel Alves, Inês Baldeiras, Emília Cortesão, José Pedro Carda, Claudia C Branco, Bárbara Oliveiros, Luísa Loureiro, Amélia Pereira, José Manuel Nascimento Costa, Ana Bela Sarmento-Ribeiro, Luisa Mota-Vieira
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) share common features: elevated oxidative stress, DNA repair deficiency, and aberrant DNA methylation. We performed a hospital-based case-control study to evaluate the association in variants of genes involved in oxidative stress, folate metabolism, DNA repair, and DNA methylation with susceptibility and prognosis of these malignancies. To that end, 16 SNPs (one per gene: CAT, CYBA, DNMT1, DNMT3A, DNMT3B, GPX1, KEAP1, MPO, MTRR, NEIL1, NFE2F2, OGG1, SLC19A1, SOD1, SOD2, and XRCC1) were genotyped in 191 patients (101 MDS and 90 AML) and 261 controls...
March 7, 2016: Molecular Carcinogenesis
Junko H Ohyashiki, Tomohiro Umezu, Kazuma Ohyashiki
PURPOSE OF REVIEW: To review the data on angiogenesis related to exosomes secreted by tumor cells in hematologic neoplasia and to elucidate the role of exosomes and exosomal miRNA in the bone marrow microenvironment, especially under hypoxic conditions. RECENT FINDINGS: Cross-talk between bone marrow tumor cells and surrounding cells, including endothelial cells, is important for tumor growth in hematologic neoplasia. In addition to conventional signaling pathways, exosomes, which are small endosome-derived vesicles containing miRNAs, can help to modulate the microenvironment without directly contacting nontumorous cells...
May 2016: Current Opinion in Hematology
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