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Myelodysplastic

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https://www.readbyqxmd.com/read/28938223/the-high-frequency-of-the-u2af1-s34y-mutation-and-its-association-with-isolated-trisomy-8-in-myelodysplastic-syndrome-in-asians-but-not-in-caucasians
#1
Seon Young Kim, Kwantae Kim, Byungjin Hwang, Kyongok Im, Si Nae Park, Jung-Ah Kim, Sang Mee Hwang, Duhee Bang, Dong Soon Lee
Mutational profiles of 153 Korean myelodysplastic syndrome (MDS) patients were investigated. Sequencing of 87 genes presented similar mutational profiles in Korean MDS patients compared with previous reports. The most frequently mutated genes were ASXL1 (22.9%), U2AF1 (16.3%), TP53 (13.7%), RUNX1 (10.5%), TET2 (10.5%), DNMT3A (8.5%), and SRSF2 (8.5%). The U2AF1 mutation frequency was higher, with different frequencies in the mutated sites of U2AF1 (S34Y, 6/25; S34F, 11/25; and Q157P 8/25). The U2AF1 S34Y mutation was strongly associated with isolated trisomy 8 (5/6, 83%) and was characterized by a younger age of MDS onset (median, 39 years)...
September 7, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28935248/comparison-of-t-lymphocyte-subsets-in-aplastic-anemia-and-hypoplastic-myelodysplastic-syndromes
#2
Hai-Fang Zhang, Zhen-Dong Huang, Xue-Run Wu, Qian Li, Zhi-Feng Yu
AIMS: This study aims to compare the proportion of peripheral blood T lymphocyte subsets and related blood cell and bone marrow cytology indexes between patients with aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hypo-MDS), and investigate the clinical identification significance. MATERIALS AND METHODS: A total of 41 patients with AA and 46 patients with hypo-MDS were collected, and the proportions of peripheral blood T lymphocyte subsets, CD3(-)CD16/CD56(+)NK cells, CD3(+)CD57(+)T-LGL cells and CD19(+)B lymphocytes were detected by flow cytometry...
September 18, 2017: Life Sciences
https://www.readbyqxmd.com/read/28934515/utility-of-fluorescence-in-situ-hybridization-panel-for-myelodysplastic-syndrome-in-evaluation-of-cytopenia-in-a-pediatric-hospital-a-5-year-retrospective-review-and-utilization-management
#3
Cynthia T Bunting, Tal Senior, Yehuda Susson, Alethia Rivera, Debra Saxe, Silvia T Bunting
Background: MDS FISH was routinely ordered together with chromosome analysis for patients with cytopenia in our hospital. The utility of MDS FISH in the pediatric population is unknown. Objective: To analyze the utility of fluorescence in situ hybridization panel for myelodysplastic syndrome (MDS FISH) in the management of patients with cytopenia. Methods: We performed a retrospective review over a 5-year period, from 2009 to 2014 to determine whether chromosome analysis (CA) plus MDS FISH added useful information compared to chromosome analysis alone...
August 1, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/28933735/clinical-outcomes-and-co-occurring-mutations-in-patients-with-runx1-mutated-acute-myeloid-leukemia
#4
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/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
#5
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/28928245/evi-and-mds-evi-are-required-for-adult-intestinal-stem-cell-formation-during-postembryonic-vertebrate-development
#6
Morihiro Okada, Yun-Bo Shi
The gene ectopic viral integration site 1 (EVI) and its variant myelodysplastic syndrome 1 (MDS)/EVI encode zinc-finger proteins that have been recognized as important oncogenes in various types of cancer. In contrast to the established role of EVI and MDS/EVI in cancer development, their potential function during vertebrate postembryonic development, especially in organ-specific adult stem cells, is unclear. Amphibian metamorphosis is strikingly similar to postembryonic development around birth in mammals, with both processes taking place when plasma thyroid hormone (T3) levels are high...
September 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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
#7
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/28927137/atypical-chronic-myeloid-leukemia-with-isochromosome-x-p10-a-case-report
#8
Masahide Yamamoto, Sayaka Suzuki, Jun-Ichi Mukae, Keisuke Tanaka, Ken Watanabe, Gaku Oshikawa, Tetsuya Fukuda, Naomi Murakami, Osamu Miura
Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Although recurrent chromosomal and genetic abnormalities are frequently observed in aCML, none are specific to this type of leukemia. The present study reported a case of aCML associated with i(X)(p10), a rare recurrent chromosomal abnormality of hematological malignancy. A 40-year-old female was referred to the Tokyo Medical and Dental University Hospital (Tokyo, Japan) due to slight leukocytosis and anemia...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926428/dna-methyltransferase-inhibitors-in-myeloid-cancer-clonal-eradication-or-clonal-differentiation
#9
Andreas Due Ørskov, Kirsten Grønbæk
DNA methyltransferase inhibitors, so-called hypomethylating agents (HMAs), are the only drugs approved for the treatment of higher-risk myelodysplastic syndromes and are widely used in this context. However, it is still unclear why some patients respond to HMAs, whereas others do not. Recent sequencing efforts have identified molecular disease entities that may be specifically sensitive to these drugs, and many attempts are being made to clarify how HMAs affect the malignant clone during treatment. Here, we review the most recent data on the clinical effects of HMAs in myeloid malignancies...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28926427/dna-methylation-targeted-drugs
#10
Elodie M Da Costa, Gabrielle McInnes, Annie Beaudry, Noël J-M Raynal
Targeting DNA hypermethylation, using nucleoside analogs, is an efficient approach to reprogram cancer cell epigenome leading to reduced proliferation, increased differentiation, recognition by the immune system, and ultimately cancer cell death. DNA methyltransferase inhibitors have been approved for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myelogenous leukemia. To improve clinical efficacy and overcome mechanisms of drug resistance, a second generation of DNA methyltransferase inhibitors has been designed and is currently in clinical trials...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28926144/characterization-of-tp53-mutations-in-low-grade-myelodysplastic-syndromes-and-myelodysplastic-syndromes-with-a-non-complex-karyotype
#11
Wei Wang, Mark J Routbort, Zhenya Tang, Chi Young Ok, Keyur P Patel, Naval Daver, Guillermo Garcia-Manero, L Jeffrey Medeiros, Sa A Wang
OBJECTIVES: Although commonly associated with high-grade myelodysplastic syndrome (MDS) and MDS with a complex karyotype, TP53 mutations also occur in low-grade MDS and MDS with a non-complex karyotype. In latter cases, their clinicopathological features and the characteristics of TP53 mutations remain poorly characterized. METHODS: 176 MDS cases with TP53 mutations were stratified and characterized based on their karyotype and histologic subtype. RESULTS: Among 176 cases, 17% had a non-complex karyotype and 24% were low-grade MDS...
September 19, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28924413/pseudovitelliform-maculopathy-associated-with-deferoxamine-toxicity-multimodal-imaging-and-electrophysiology-of-a-rare-entity
#12
Kelly M Bui, SriniVas R Sadda, Hani Salehi-Had
Deferoxamine is a commonly used chelating agent for secondary hemochromatosis. We report a rare retinal manifestation of deferoxamine toxicity in a 68-year-old man and provide supporting multimodal imaging and electrophysiology. The patient had iron overload related to transfusion-dependent myelodysplastic syndrome and developed a pseudovitelliform macular lesion related to deferoxamine toxicity. We also describe for the first time the worsening of this maculopathy on deferasirox, an alternative chelating agent...
2017: Digital Journal of Ophthalmology: DJO
https://www.readbyqxmd.com/read/28923296/malignant-transformation-of-oral-leukoplakia-in-a-patient-with-dyskeratosis-congenita
#13
Michelle Bongiorno, Shayna Rivard, Daniel Hammer, Joshua Kentosh
Dyskeratosis congenita (DC) is a rare, inherited, bone marrow failure syndrome caused by premature telomere shortening. The classic mucocutaneous triad of clinical features comprises reticulated skin pigmentation, nail dysplasia, and oral leukoplakia. Multiple somatic features, including bone marrow failure, pulmonary fibrosis, and liver disease, are also common. DC significantly increases the risk for malignant transformation, including myelodysplastic syndrome, acute myeloid leukemia, head and neck squamous cell carcinoma, and anogenital cancer...
August 12, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28918304/haploidentical-transplantation-for-older-patients-with-acute-myeloid-leukemia-and-myelodysplastic-syndrome
#14
Stefan O Ciurea, Mithun V Shah, Rima M Saliba, Sameh Gaballa, Piyanuch Kongtim, Gabriela Rondon, Julianne Chen, Whitney Wallis, Kai Cao, Marina Konopleva, Naval Daver, Jorge Cortes, Farhad Ravandi, Amin Alousi, Sairah Ahmed, Uday Popat, Simrit Parmar, Qaiser Bashir, Oran Betul, Chitra Hosing, Elizabeth J Shpall, Katayoun Rezvani, Issa F Khouri, Partow Kebriaei, Richard E Champlin
Allogeneic stem cell transplant (ASCT) with HLA matched donors is increasingly used for older patients with AML/MDS. It remains unclear if haploidentical transplantation (haploSCT) is a suitable option for older patients with this disease. We analyzed 43 patients with AML/MDS (median age 61 years) who underwent a haploSCT at our institution. All the patients received a fludarabine-melphalan-based reduced-intensity conditioning regimen and post-transplant cyclophosphamide-based GVHD prophylaxis. Except one patient who had early death, the remaining 42 patients (98%) engrafted donor cells...
September 13, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28914552/myelodysplastic-syndromes-mds-in-regular-care-in-germany-the-oldest-patients-come-to-the-fore
#15
Hans Tilman Steinmetz, Ulrich Germing, Annette Sauer, Bernd Lathan, Rüdiger Liersch, Hans Tesch, Jörg Heßling, Enno Moorahrend, Jens Uhlig, Marcel Reiser, Roja Wahdat, Norbert Gattermann, Uwe Totzke, Stephan Schmitz
No abstract text is available yet for this article.
September 15, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28913766/computational-modeling-and-treatment-identification-in-the-myelodysplastic-syndromes
#16
REVIEW
Leylah M Drusbosky, Christopher R Cogle
PURPOSE OF REVIEW: This review discusses the need for computational modeling in myelodysplastic syndromes (MDS) and early test results. RECENT FINDINGS: As our evolving understanding of MDS reveals a molecularly complicated disease, the need for sophisticated computer analytics is required to keep track of the number and complex interplay among the molecular abnormalities. Computational modeling and digital drug simulations using whole exome sequencing data input have produced early results showing high accuracy in predicting treatment response to standard of care drugs...
September 14, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28912173/secondary-malignant-neoplasms-progression-free-survival-and-overall-survival-in-patients-treated-for-hodgkin-lymphoma-a-systematic-review-and-meta-analysis-of-randomized-clinical-trials
#17
Dennis A Eichenauer, Ingrid Becker, Ina Monsef, Nicholas Chadwick, Vitaliana de Sanctis, Massimo Federico, Catherine Fortpied, Alessandro M Gianni, Michel Henry-Amar, Peter Hoskin, Peter Johnson, Stefano Luminari, Monica Bellei, Alessandro Pulsoni, Matthew R Sydes, Pinuccia Valagussa, Simonetta Viviani, Andreas Engert, Jeremy Franklin
Treatment intensification to maximize disease control and reduced-intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the present meta-analysis based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto's method as time-to-event outcomes...
September 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28910695/mds-classification-is-improving-in-an-era-of-the-who-2016-criteria-of-mds-a-population-based-analysis-among-9159-mds-patients-diagnosed-in-the-netherlands
#18
Avinash G Dinmohamed, Otto Visser, Eduardus F M Posthuma, Peter C Huijgens, Pieter Sonneveld, Arjan A van de Loosdrecht, Mojca Jongen-Lavrencic
BACKGROUND: Morphologic and cytogenetic assessments are required to characterize diagnostic and prognostic features of myelodysplastic syndromes (MDS). We assessed whether these assessments were performed among newly diagnosed MDS patients in the Netherlands. METHODS: MDS cases were retrieved from the nationwide Netherlands Cancer Registry (N=9159; period 2001-2014) and the regional PHAROS MDS registry (N=676; period 2008-2011). RESULTS: The proportion of unclassified MDS decreased from 58% in 2001 to 13% in 2014...
September 11, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28905389/the-first-reported-case-of-concurrent-trimethoprim-sulfamethoxazole-induced-immune-hemolytic-anemia-and-thrombocytopenia
#19
Yevgeniy A Linnik, Edison W Tsui, Isabella W Martin, Zbigniew M Szczepiorkowski, Gregory A Denomme, Jerome L Gottschall, John M Hill, Nancy M Dunbar
BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) and drug-induced immune thrombocytopenia (DIIT) are rare but dangerous complications of pharmacotherapy that may be underrecognized in hematopoietic stem cell transplant (HSCT) patients due to overlap of signs and symptoms with those of more common disease processes. CASE REPORT: A 61-year-old woman with NK-cell deficiency and GATA-2-associated myelodysplastic syndrome, status post-recent allogeneic HSCT (Day +58), presented with 3 days of acute-onset severe back pain, muscle cramps, and increasingly dark urine...
September 14, 2017: Transfusion
https://www.readbyqxmd.com/read/28905323/phase-i-study-of-panobinostat-and-5-azacitidine-in-japanese-patients-with-myelodysplastic-syndrome-or-chronic-myelomonocytic-leukemia
#20
Yukio Kobayashi, Wataru Munakata, Michinori Ogura, Toshiki Uchida, Masafumi Taniwaki, Tsutomu Kobayashi, Fumika Shimada, Masataka Yonemura, Fumiko Matsuoka, Takeshi Tajima, Kimikazu Yakushijin, Hironobu Minami
The current therapy for high-risk myelodysplastic syndrome (MDS) involves repeated cycles of the DNA demethylating agent 5-azacitidine (5-Aza), but combination treatments have been proposed to improve patient outcomes. We performed a phase Ib study to investigate the safety and tolerability of 5-Aza (75 mg/m(2)) combined with the histone deacetylase inhibitor panobinostat (PAN) in adult Japanese patients with MDS or chronic myelomonocytic leukemia (CMML). Eleven patients were enrolled; five received 20 mg PAN + 5-Aza and six received 30 mg PAN + 5-Aza...
September 13, 2017: International Journal of Hematology
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