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myelodysplastic syndrome review

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https://www.readbyqxmd.com/read/28449370/the-burden-of-autoimmunity-in-myelodysplastic-syndromes
#1
REVIEW
Claudio Fozza
The clinical history of patients with myelodysplastic syndromes (MDS) is characterised by bone marrow insufficiency as well as by the possible evolution into acute leukaemia. However a number of reports highlight the frequent occurrence of autoimmune manifestations involving different sites and organs. The present review will first describe the clinical pictures most often observed in MDS patients. The actual burden of autoimmunity will be then addressed by focusing on the few available registry studies. Finally, the potential collateral impact of specific treatments for MDS on the evolution of autoimmune disorders will be considered...
April 27, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28446323/-role-of-aberrant-splicing-in-pathogenesis-of-myelodysplastic-syndromes-review
#2
Lin Li, Zhi-Jian Xiao, Xue-Mei Sun
The spectrum of genetic abnormalities in myelodysplastic syndromes(MDS) has been revealed by high-throughput sequencing. However, the functional role of these mutations in occurrence and development of MDS was not delineated. The mutations in splicing factors have been identified as the commonest gene mutations in MDS. Recently, it was reported that the mutated or dysregulated splicing factors, including SF3B1, SRSF2 and U2AF1, attribute to aberrant mRNA splicing, which leads to hematopoietic dysfunction and drives MDS...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28430954/increased-multinucleated-megakaryocytes-as-an-isolated-finding-in-bone-marrow-%C3%A2-a-rare-finding-and-its-clinical-significance
#3
Majd D Jawad, Ronald S Go, Kaaren K Reichard, Min Shi
Objectives: Multinucleated megakaryocytes are a unique morphologic form of megakaryocytes characterized by multiple, distinctly separated nuclei. We investigated whether increased multinucleated megakaryocytes (≥25%) in otherwise normal-appearing bone marrow were associated with the development of a myelodysplastic syndrome (MDS). Methods: We retrospectively reviewed the medical records and bone marrow biopsy specimens of patients evaluated at our institution from 2011 to 2015 that met all of the following criteria: (1) 25% or more multinucleated megakaryocytes, (2) no other dysplastic features, (3) absence of a myeloid neoplasm, and (4) absence of neoplastic karyotypic abnormalities...
November 1, 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28419413/long-term-outcomes-secondary-malignancies-and-stem-cell-collection-following-bendamustine-in-patients-with-previously-treated-non-hodgkin-lymphoma
#4
Peter Martin, Zhengming Chen, Bruce D Cheson, Katherine S Robinson, Michael Williams, Saurabh A Rajguru, Jonathan W Friedberg, Richard H van der Jagt, Ann S LaCasce, Robin Joyce, Kristen N Ganjoo, Nancy L Bartlett, Bernard Lemieux, Ari VanderWalde, Jordan Herst, Jeffrey Szer, Michael H Bar, Fernando Cabanillas, Anthony J Dodds, Paul G Montgomery, Bryn Pressnail, Tricia Ellis, Mitchell R Smith, John P Leonard
Despite the long history of bendamustine as treatment for indolent non-Hodgkin lymphoma, long-term efficacy and toxicity data are minimal. We reviewed long-term data from three clinical trials to characterize the toxicity and efficacy of patients receiving bendamustine. Data were available for 149 subjects at 21 sites. The median age was 60 years at the start of bendamustine (range 39-84), and patients had received a median of 3 prior therapies. The histologies included grades 1-2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n = 2) and not reported (n = 2)...
April 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28388253/lenalidomide-in-the-treatment-of-chronic-lymphocytic-leukemia
#5
Gilad Itchaki, Jennifer R Brown
Lenalidomide is an immunomodulatory drug (IMiD) with a unique mode of action (MOA) that may vary across disease-type. It is currently approved in multiple myeloma (MM), myelodysplastic syndrome (MDS) and mantle cell lymphoma (MCL), yet is also clinically active in a host of lymphoproliferative diseases, including chronic lymphocytic leukemia (CLL). Due to its protean effects on the immune system, lenalidomide may be particularly appealing in CLL, which is distinct in its ability to evade immune recognition and cause immunosuppression...
May 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28359286/the-double-edged-sword-of-re-expression-of-genes-by-hypomethylating-agents-from-viral-mimicry-to-exploitation-as-priming-agents-for-targeted-immune-checkpoint-modulation
#6
REVIEW
Florian Wolff, Michael Leisch, Richard Greil, Angela Risch, Lisa Pleyer
Hypomethylating agents (HMAs) have been widely used over the last decade, approved for use in myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). The proposed central mechanism of action of HMAs, is the reversal of aberrant methylation in tumor cells, thus reactivating CpG-island promoters and leading to (re)expression of tumor suppressor genes. Recent investigations into the mode of action of azacitidine (AZA) and decitabine (DAC) have revealed new molecular mechanisms that impinge on tumor immunity via induction of an interferon response, through activation of endogenous retroviral elements (ERVs) that are normally epigenetically silenced...
March 31, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28359242/small-molecule-inhibitors-of-epigenetic-mutations-as-compelling-drug-targets-for-myelodysplastic-syndromes
#7
Bani Bandana Ganguly
BACKGROUND: Involvement of mutations in epigenetic mechanism in development of heterogeneous MDS and its evolution to AML has been understood with at least one mutation and median of 2-3 mutations of the landscapes of driver mutations in ~40 genes described >90% MDS patients. Exclusivity and cooperating effects of mutations have directed therapeutic implementation with hypomethylating agents and identified a number of first-in-class small molecules as inhibitors of mutational expression...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28356770/breast-cancer-in-patients-with-li-fraumeni-syndrome-a-case-series-study-and-review-of-literature
#8
Amara G Nandikolla, Sangeetha Venugopal, Jesus Anampa
BACKGROUND: Li-Fraumeni Syndrome (LFS) is a rare disease with autosomal dominant inheritance linked to germline mutations of tumor suppressor gene TP53. These patients are predisposed to malignancies such as sarcoma, breast cancer, leukemia, and other malignancies. Breast cancer, the most common malignancy in adult patients with LFS, has an early-onset presentation and is usually treated as per the guidelines for the general population due to the limited literature about breast cancer in LFS...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28351181/prognostic-models-in-predicting-outcomes-in-myelodysplastic-syndromes-after-hypomethylating-agent-failure
#9
Sagar S Patel, Mikkael A Sekeres, Aziz Nazha
Myelodysplastic syndromes (MDS) are clonal stem cell disorders marked by bone marrow failure with varying degrees of cytopenias. MDS are characterized by the accumulation of complex genetic alterations that influence disease pathogenesis and outcomes. Given the heterogeneity of MDS patients, multiple prognostic scoring systems have been developed to predict patient outcomes. Most focus primarily on untreated patients in whom outcomes are predicted accurately only at diagnosis; their application dynamically, during the disease course and especially after hypomethylating agent (HMA) failure, may not be accurate...
March 28, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28343141/survival-outcomes-in-iron-chelated-and-non-chelated-patients-with-lower-risk-myelodysplastic-syndromes-review-and-pooled-analysis-of-observational-studies
#10
EDITORIAL
Ivo Abraham, Majed Al Yami, Seongseok Yun, Hee-Ju Kim, Nicole D Vincelette, Ali McBride, Karen MacDonald
No abstract text is available yet for this article.
March 18, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28321924/infectious-complications-in-patients-with-myelodysplastic-syndromes-a-review-of-the-literature-with-emphasis-on-patients-treated-with-5-azacitidine
#11
REVIEW
Markus Radsak, Uwe Platzbecker, Cornelia S Schmidt, Wolf-Karsten Hofmann, Florian Nolte
Myelodysplastic Syndromes are oligo-clonal stem cell disorders that are associated with cytopenias in the peripheral blood. Major causes for morbidity and mortality in myelodysplastic syndromes (MDS) patients are infections mostly due to bacteria or fungi. Beside leucopenia per se in affected patients, function of white blood cells particularly that of neutrophils seems to be impaired. Here we summarize the available data on infections in MDS patients in general and particularly those treated with 5-azacitidine...
March 21, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28299658/clinical-relevance-of-runx1-and-cbfb-alterations-in-acute-myeloid-leukemia-and-other-hematological-disorders
#12
Klaus H Metzeler, Clara D Bloomfield
The translocation t(8;21), leading to a fusion between the RUNX1 gene and the RUNX1T1 locus, was the first chromosomal translocation identified in cancer. Since the first description of this balanced rearrangement in a patient with acute myeloid leukemia (AML) in 1973, RUNX1 translocations and point mutations have been found in various myeloid and lymphoid neoplasms. In this chapter, we summarize the currently available data on the clinical relevance of core binding factor gene alterations in hematological disorders...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28297619/clinical-implications-of-genetic-mutations-in-myelodysplastic-syndrome
#13
James A Kennedy, Benjamin L Ebert
Myelodysplastic syndrome (MDS) is clonal disorder characterized by ineffective hematopoiesis and a tendency to evolve into acute myeloid leukemia (AML). Genetic studies have enabled the identification of a set of recurrently mutated genes central to the pathogenesis of MDS, which can be organized into a limited number of cellular processes, including RNA splicing, epigenetic and traditional transcriptional regulation, and signal transduction. The sequential accumulation of mutations drives disease evolution from asymptomatic clonal hematopoiesis to frank MDS, and, ultimately, to secondary AML...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28293409/myelodysplastic-syndromes-and-iron-chelation-therapy
#14
REVIEW
Emanuele Angelucci, Silvana Anna Maria Urru, Federica Pilo, Alberto Piperno
Over recent decades we have been fortunate to witness the advent of new technologies and of an expanded knowledge and application of chelation therapies to the benefit of patients with iron overload. However, extrapolation of learnings from thalassemia to the myelodysplastic syndromes (MDS) has resulted in a fragmented and uncoordinated clinical evidence base. We're therefore forced to change our understanding of MDS, looking with other eyes to observational studies that inform us about the relationship between iron and tissue damage in these subjects...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28293405/diagnostic-utility-of-flow-cytometry-in-myelodysplastic-syndromes
#15
REVIEW
Matteo G Della Porta, Cristina Picone
The pathological hallmark of myelodysplastic syndromes (MDS) is marrow dysplasia, which represents the basis of the WHO classification of these disorders. This classification provides clinicians with a useful tool for defining the different subtypes of MDS and individual prognosis. The WHO proposal has raised some concern regarding minimal diagnostic criteria particularly in patients with normal karyotype without robust morphological markers of dysplasia (such as ring sideroblasts or excess of blasts). Therefore, there is clearly need to refine the accuracy to detect marrow dysplasia...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28285807/a-brighter-side-to-thalidomide-its-potential-use-in-immunological-disorders
#16
REVIEW
David Millrine, Tadamitsu Kishimoto
Thalidomide and its derivatives are immunomodulatory drugs (IMiDs) known for their sedative, teratogenic, anti-angiogenic, and anti-inflammatory properties. Commonly used in the treatment of cancers such as multiple myeloma and myelodysplastic syndrome (MDS), IMiDs have also been used in the treatment of an inflammatory skin pathology associated with Hansen's disease/leprosy. They have also shown promise in the treatment of autoimmune disorders including systemic lupus erythmatosus (SLE) and inflammatory bowel disease (IBD)...
April 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28278704/incidence-etiology-and-timing-of-infections-following-azacitidine-therapy-for-myelodysplastic-syndromes
#17
Jason A Trubiano, Michael Dickinson, Karin A Thursky, Timothy Spelman, John F Seymour, Monica A Slavin, Leon J Worth
We examine the infective complications occurring during azacitidine (AZA) therapy in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). A retrospective review of patients receiving ≥1 cycle of AZA for MDS or AML was performed. Patient demographics, infection prophylaxis/episodes and outcomes were evaluated. Sixty eight patients received 884 AZA cycles. Bacterial infections occurred in 25% of cycle-1 and 27% of cycle-2 AZA therapy. Febrile neutropenia complicated 5.3% of AZA cycles, bacteremia 2% and invasive Aspergillosis 0...
February 28, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28277851/management-of-lower-risk-myelodysplastic-syndromes-without-del5q-current-approach-and-future-trends
#18
Maximilian Stahl, Amer M Zeidan
Myelodysplastic syndromes (MDS) are characterized by progressive bone marrow failure manifesting as blood cytopenia and a variable risk of progression into acute myeloid leukemia. MDS is heterogeneous in biology and clinical behavior. MDS is generally divided into lower-risk (LR) or higher-risk (HR) MDS. Goals of care in HR-MDS is changing the natural history of the disease, whereas in LR-MDS it is symptom control and quality of life. Areas covered: We review the epidemiology, tools of risk assessment, and the available therapeutic modalities for LR-MDS...
February 21, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28275823/beyond-immune-thrombocytopenia-the-evolving-role-of-thrombopoietin-receptor-agonists
#19
REVIEW
Francesco Rodeghiero, Giuseppe Carli
Since its discovery, the thrombopoietin (TPO) pathway has been an important pharmaceutical target for the treatment of thrombocytopenia. The first generation of TPO mimetics included peptide agents sharing homology with endogenous TPO, but these introduced a risk of antibody formation to endogenous TPO and were not successful. However, second-generation TPO mimetics or TPO receptor agonists (RAs) are currently being used to treat thrombocytopenia associated with a number of conditions, such as immune thrombocytopenia (ITP), severe aplastic anaemia (SAA), and hepatitis C virus-associated chronic liver disease...
March 8, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28259746/acute-myeloid-leukemia-in-a-patient-with-thrombocytopenia-with-absent-radii-a-case-report-and-review-of-the-literature
#20
Maximilian Jameson-Lee, Katherine Chen, Ellen Ritchie, Tsiporah Shore, Omar Al-Khattab, Usama Gergis
Thrombocytopenia with absent radii (TAR) syndrome is a rare congenital disorder characterized by low platelet counts of various severity, bilateral absent radii but thumbs are usually present. TAR syndrome is not generally associated with bone marrow failure or malignancy. Janus kinase-2, myeloproliferative leukemia protein, and calreticulin are not mutated in TAR patients. Only four cases of leukemia were reported in TAR patients in the literature: three acute myeloid leukemia (AML) and one acute lymphoblastic leukemia...
February 24, 2017: Hematology/oncology and Stem Cell Therapy
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