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myelodysplastic syndrome review

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https://www.readbyqxmd.com/read/29054020/unraveling-the-mechanisms-behind-iron-overload-and-ineffective-hematopoiesis-in-myelodysplastic-syndromes
#1
REVIEW
Emanuele Angelucci, Paolo Cianciulli, Carlo Finelli, Cristina Mecucci, Maria Teresa Voso, Sante Tura
Myelodysplastic syndromes (MDS) are a group of clonally-acquired blood disorders characterized by ineffective hematopoiesis leading to cytopenias. Red blood cell transfusions are an important component of supportive care in patients with MDS. Prolonged exposure to transfusions can lead to iron overload, which results in iron-induced toxicity caused by the production of reactive oxygen species (ROS). ROS accumulation has detrimental effects also on hematopoietic stem cells and may contribute to MDS progression...
October 5, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29038614/dna-methylation-events-as-markers-for-diagnosis-and-management-of-acute-myeloid-leukemia-and-myelodysplastic-syndrome
#2
REVIEW
Geórgia Muccillo Dexheimer, Jayse Alves, Laura Reckziegel, Gabrielle Lazzaretti, Ana Lucia Abujamra
During the onset and progression of hematological malignancies, many changes occur in cellular epigenome, such as hypo- or hypermethylation of CpG islands in promoter regions. DNA methylation is an epigenetic modification that regulates gene expression and is a key event for tumorigenesis. The continuous search for biomarkers that signal early disease, indicate prognosis, and act as therapeutic targets has led to studies investigating the role of DNA in cancer onset and progression. This review focuses on DNA methylation changes as potential biomarkers for diagnosis, prognosis, response to treatment, and early toxicity in acute myeloid leukemia and myelodysplastic syndrome...
2017: Disease Markers
https://www.readbyqxmd.com/read/28986033/splicing-factor-mutations-in-the-myelodysplastic-syndromes-target-genes-and-therapeutic-approaches
#3
REVIEW
Richard N Armstrong, Violetta Steeples, Shalini Singh, Andrea Sanchi, Jacqueline Boultwood, Andrea Pellagatti
Mutations in splicing factor genes (SF3B1, SRSF2, U2AF1 and ZRSR2) are frequently found in patients with myelodysplastic syndromes (MDS), suggesting that aberrant spliceosome function plays a key role in the pathogenesis of MDS. Splicing factor mutations have been shown to result in aberrant splicing of many downstream target genes. Recent functional studies have begun to characterize the splicing dysfunction in MDS, identifying some key aberrantly spliced genes that are implicated in disease pathophysiology...
September 22, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28983777/therapy-for-chronic-myelomonocytic-leukemia-in-a-new-era
#4
REVIEW
Tamara K Moyo, Michael R Savona
Chronic myelomonocytic leukemia (CMML) is a myeloid malignancy which shares clinical and morphologic features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs) and is classified by the WHO as an MDS/MPN. The defining feature of CMML is clonal hematopoiesis that results in peripheral monocytosis. The benefit of early treatment is currently unclear, and treatment may be held until the disease exhibits accelerated blast counts or the patient becomes symptomatic. Optimal treatments for CMML are not well defined...
October 6, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28978837/treatment-for-myelodysplastic-syndrome-with-a-focus-on-the-low-risk-group
#5
Akihiko Gotoh
Myelodysplastic syndrome (MDS) is a group of clonal disorders affecting hematopoietic stem cells. Thus, the only potential curative therapy is hematopoietic stem cell transplantation (HSCT). Indeed, for high-risk patients with MDS, who have a higher anticipated risk of leukemic transformation and shorter survival, HSCT is the first choice for eligible patients. DNA hypomethylating agents, the only agents proved to prolong survival, are used in non-HSCT-eligible high-risk patients with MDS. In contrast, due to high transplant-related mortality rate, treatment strategies other than HSCT are mainly applied for the low-risk group with expected long-term survival...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28977983/techniques-for-detecting-chromosomal-aberrations-in-myelodysplastic-syndromes
#6
REVIEW
Qibin Song, Min Peng, Yuxin Chu, Shiang Huang
Myelodysplastic syndromes (MDS) are a group of heterogeneous hematologic diseases. Chromosomal aberrations are important for the initiation, development, and progression of MDS. Detection of chromosomal abnormalities in MDS is important for categorization, risk stratification, therapeutic selection, and prognosis evaluation of the disease. Recent progress of multiple techniques has brought powerful molecular cytogenetic information to reveal copy number variation, uniparental disomy, and complex chromosomal aberrations in MDS...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28976600/midostaurin-a-new-oral-agent-targeting-flt3-mutant-acute-myeloid-leukemia
#7
Lindsay C Stansfield, Daniel A Pollyea
Acute myeloid leukemia (AML), a clonal hematologic malignancy that results in bone marrow failure, is the most common acute leukemia in adults (median age of diagnosis 67 years), and treatment options, especially in the elderly population, are limited. Induction chemotherapy with 7+3, the combination of continuous-infusion cytarabine and intermittent dosing of an anthracycline administered over 7 and 3 days, respectively, has remained the standard of care since its introduction in 1973 in the United States...
October 4, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28962071/thrombopoietin-mimetics-for-patients-with-myelodysplastic-syndromes
#8
REVIEW
Helga Dodillet, Karl-Anton Kreuzer, Ina Monsef, Nicole Skoetz
BACKGROUND: Myelodysplastic syndrome (MDS) is one of the most frequent haematologic malignancies of the elderly population and characterised by progenitor cell dysplasia with ineffective haematopoiesis and a high rate of transformation to acute myeloid leukaemia (AML). Thrombocytopenia represents a common problem for patients with MDS. ranging from mild to serious bleeding events and death. To manage thrombocytopenia, the current standard treatment includes platelet transfusion, unfortunately leading to a range of side effects...
September 30, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28958288/optimizing-the-use-of-hypomethylating-agents-in-myelodysplastic-syndromes-selecting-the-candidate-predicting-the-response-and-enhancing-the-activity
#9
REVIEW
Yazan Madanat, Mikkael A Sekeres
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders that have a substantial impact on patients' quality of life, in addition to causing significant morbidity and mortality. The hypomethylating agents (HMAs) azacitidine and decitabine are approved for use in the United States and in Europe for the treatment of MDS or acute myeloid leukemia (AML) and, in the case of azacitidine, prolong survival in higher-risk patients. Neither is curative, though, and given the lack of clear treatment guidelines after HMA treatment failure, it is imperative to optimize patient selection and identify the right timing of HMA treatment initiation and response evaluation to maximize patient benefit...
July 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28947904/mesenchymal-stem-cells-in-myeloid-malignancies-a-focus-on-immune-escaping-and-therapeutic-implications
#10
REVIEW
Nicola Stefano Fracchiolla, Bruno Fattizzo, Agostino Cortelezzi
The importance of the bone marrow microenvironment forming the so-called niche in physiologic hemopoiesis is largely known, and recent evidences support the presence of stromal alterations from the molecular to the cytoarchitectural level in hematologic malignancies. Various alterations in cell adhesion, metabolism, cytokine signaling, autophagy, and methylation patterns of tumor-derived mesenchymal stem cells have been demonstrated, contributing to the genesis of a leukemic permissive niche. This niche allows both the ineffective haematopoiesis typical of myelodysplastic syndromes and the differentiation arrest, proliferation advantage, and clone selection which is the hallmark of acute myeloid leukemia...
2017: Stem Cells International
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
#11
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/28927162/myelodysplastic-syndrome-unclassifiable-mds-u-with-1-blasts-is-a-distinct-subgroup-of-mds-u-with-a-poor-prognosis
#12
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/28926428/dna-methyltransferase-inhibitors-in-myeloid-cancer-clonal-eradication-or-clonal-differentiation
#13
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/28913766/computational-modeling-and-treatment-identification-in-the-myelodysplastic-syndromes
#14
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
#15
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 meta-analysis herein, 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...
October 2017: Haematologica
https://www.readbyqxmd.com/read/28905389/the-first-reported-case-of-concurrent-trimethoprim-sulfamethoxazole-induced-immune-hemolytic-anemia-and-thrombocytopenia
#16
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/28898985/lineage-switch-between-b-lymphoblastic-leukemia-and-acute-myeloid-leukemia-intermediated-by-occult-myelodysplastic-neoplasm-two-cases-of-adult-patients-with-evidence-of-genomic-instability-and-clonal-selection-by-chemotherapy
#17
Bin Wu, Rachel Jug, Catherine Luedke, Pu Su, Catherine Rehder, Chad McCall, Anand S Lagoo, Endi Wang
Objectives: Lineage switch occurs in rare leukemias, and the mechanism is unclear. We report two cases of B-lymphoblastic leukemia (B-ALL) relapsed as acute myeloid leukemia (AML). Methods: Retrospective review of clinical and laboratory data. Results: Complex cytogenetic abnormalities were detected in B-ALL for both cases with subclone heterogeneity. Postchemotherapy marrow biopsies showed trilineage hematopoiesis without detectable B-ALL...
August 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28894557/clinico-pathological-spectrum-and-novel-karyotypic-findings-in-myelodysplastic-syndrome-experience-of-tertiary-care-center-in-india
#18
Ruchi Gupta, Khaliqur Rahman, Manish Kumar Singh, Surabhi Kumari, Geeta Yadav, Soniya Nityanand
BACKGROUND: Myelodysplastic syndrome (MDS) is a heterogeneous disorder characterized clinically by the presence of cytopenia/s. Limited data are available about the morphological spectrum and cytogenetic profile of Indian MDS patients. The aim of the study was to ascertain the clinico-pathological, morphological and cytogenetic spectrum of Indian MDS patients. MATERIAL AND METHODS: A retrospective analysis of all patients diagnosed with MDS from June 2012 to December 2016 was performed...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28891083/a-nationwide-survey-of-hypoplastic-myelodysplastic-syndrome-a-multicenter-retrospective-study
#19
Takashi Kobayashi, Yasuhito Nannya, Motoshi Ichikawa, Kenji Oritani, Yuzuru Kanakura, Akihiro Tomita, Hitoshi Kiyoi, Masayoshi Kobune, Junji Kato, Hiroshi Kawabata, Motohiro Shindo, Yoshihiro Torimoto, Yuji Yonemura, Nobuyoshi Hanaoka, Hideki Nakakuma, Daisuke Hasegawa, Atsushi Manabe, Naohito Fujishima, Nobuharu Fujii, Mitsune Tanimoto, Yasuyoshi Morita, Akira Matsuda, Atsushi Fujieda, Naoyuki Katayama, Haruhiko Ohashi, Hirokazu Nagai, Yoshiki Terada, Masayuki Hino, Ken Sato, Naoshi Obara, Shigeru Chiba, Kensuke Usuki, Masatsugu Ohta, Osamu Imataki, Makiko Uemura, Tomoiku Takaku, Norio Komatsu, Akira Kitanaka, Kazuya Shimoda, Kenichiro Watanabe, Kaoru Tohyama, Akifumi Takaori-Kondo, Hideo Harigae, Shunya Arai, Yasushi Miyazaki, Keiya Ozawa, Mineo Kurokawa
Hypoplastic myelodysplastic syndrome (hMDS) is a distinct entity with bone marrow (BM) hypocellularity and the risk of death from BM failure (BMF). To elucidate the characteristics of hMDS, the data of 129 patients diagnosed between April 2003 and March 2012 were collected from 20 institutions and the central review team of the National Research Group on Idiopathic Bone Marrow Failure Syndromes, and compared with 115 non-hMDS patients. More RA and fewer CMMoL and RAEB-t in French-American-British (FAB) and more RCUD and MDS-U and fewer RCMD in World Health Organization (WHO) classifications were found in hMDS than non-hMDS with significant differences...
September 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28888996/mutations-of-rna-splicing-factors-in-hematological-malignancies
#20
REVIEW
Girish C Shukla, Jagjit Singh
Systematic large-scale cancer genomic studies have produced numerous significant findings. These studies have not only revealed new cancer-promoting genes, but they also have identified cancer-promoting functions of previously known "housekeeping" genes. These studies have identified numerous mutations in genes which play a fundamental role in nuclear precursor mRNA splicing. Somatic mutations and copy number variation in many of the splicing factors which participate in the formation of multiple spliceosomal complexes appear to play a role in many cancers and in particular in myelodysplastic syndromes (MDS)...
November 28, 2017: Cancer Letters
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