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Myelodysplastic syndrome and environment

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https://www.readbyqxmd.com/read/30305498/-clonal-hematopoiesis-in-aplastic-anemia
#1
Hideki Makishima
Aplastic anemia (AA) is an autoimmune-mediated bone marrow failure syndrome. While AA is not a malignant disease, clonal hematopoiesis is commonly detected via next-generation sequencing and single nucleotide polymorphism (SNP) array. Clonal hematopoiesis in AA has been confirmed by the detection of classic X chromosome skewing, PNH clones, UPD6p, and various mutations. The most frequent genetic events in AA are UPD6p and somatic mutations in BCOR/BCORL1, PIGA, DNMT3A, and ASXL1. While some mutations are common between patients with AA and healthy elderly donors, UPD6p and PIGA mutations are specific to clonal cells in AA, which need to manage their highly autoimmune extrinsic environment...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/30250186/infection-perturbs-bach2-and-bach1-dependent-erythroid-lineage-choice-to-cause-anemia
#2
Hiroki Kato, Ari Itoh-Nakadai, Mitsuyo Matsumoto, Yusho Ishii, Miki Watanabe-Matsui, Masatoshi Ikeda, Risa Ebina-Shibuya, Yuki Sato, Masahiro Kobayashi, Hironari Nishizawa, Katsushi Suzuki, Akihiko Muto, Tohru Fujiwara, Yasuhito Nannya, Luca Malcovati, Mario Cazzola, Seishi Ogawa, Hideo Harigae, Kazuhiko Igarashi
Elucidation of how the differentiation of hematopoietic stem and progenitor cells (HSPCs) is reconfigured in response to the environment is critical for understanding the biology and disorder of hematopoiesis. Here we found that the transcription factors (TFs) Bach2 and Bach1 promoted erythropoiesis by regulating heme metabolism in committed erythroid cells to sustain erythroblast maturation and by reinforcing erythroid commitment at the erythro-myeloid bifurcation step. Bach TFs repressed expression of the gene encoding the transcription factor C/EBPβ, as well as that of its target genes encoding molecules important for myelopoiesis and inflammation; they achieved the latter by binding to their regulatory regions also bound by C/EBPβ...
October 2018: Nature Immunology
https://www.readbyqxmd.com/read/30219650/differing-clinical-features-between-japanese-and-caucasian-patients-with-myelodysplastic-syndromes-analysis-from-the-international-working-group-for-prognosis-of-mds
#3
Yasushi Miyazaki, Heinz Tuechler, Guillermo Sanz, Julie Schanz, Guillermo Garcia-Manero, Francesc Solé, John M Bennett, David Bowen, Pierre Fenaux, Francois Dreyfus, Hagop Kantarjian, Andrea Kuendgen, Luca Malcovati, Mario Cazzola, Jaroslav Cermak, Christa Fonatsch, Michelle M Le Beau, Marilyn L Slovak, Valeria Santini, Michael Lübbert, Jaroslaw Maciejewski, Sigrid Machherndl-Spandl, Silvia M M Magalhaes, Michael Pfeilstöcker, Mikkael A Sekeres, Wolfgang R Sperr, Reinhard Stauder, Sudhir Tauro, Peter Valent, Teresa Vallespi, Arjan A van de Loosdrecht, Ulrich Germing, Detlef Haase, Peter L Greenberg
Clinical features of myelodysplastic syndromes (MDS) could be influenced by many factors, such as disease intrinsic factors (e.g., morphologic, cytogenetic, molecular), extrinsic factors (e.g, management, environment), and ethnicity. Several previous studies have suggested such differences between Asian and European/USA countries. In this study, to elucidate potential differences in primary untreated MDS between Japanese (JPN) and Caucasians (CAUC), we analyzed the data from a large international database collected by the International Working Group for Prognosis of MDS (300 and 5838 patients, respectively)...
September 6, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29286493/twenty-five-years-of-the-national-academy-of-medical-sciences-of-ukraine-progress-and-priorities-for-future-of-radiation-medicine-and-biology
#4
D Bazyka
After the creation of the Academy of Medical Sciences of Ukraine in 1993 the Research Center for Radiation Medicine was among the first institutions to join the Academy (fig. 1). Estab lishing the Academy was among the first steps of the independent Ukrainian government and aimed to provide a high level health care for population. It was extremely needed for the minimization of Chornobyl medical consequences. This choice was related to a growing recognition of the scientific research in fulfilling the Сenter's mission - study of the effects of low dose radiation on human body and radiation protection of the exposed population...
December 2017: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/28835720/therapy-related-myeloid-neoplasms-when-genetics-and-environment-collide
#5
REVIEW
Megan E McNerney, Lucy A Godley, Michelle M Le Beau
Therapy-related myeloid neoplasms (t-MN) arise as a late effect of chemotherapy and/or radiation administered for a primary condition, typically a malignant disease, solid organ transplant or autoimmune disease. Survival is measured in months, not years, making t-MN one of the most aggressive and lethal cancers. In this Review, we discuss recent developments that reframe our understanding of the genetic and environmental aetiology of t-MN. Emerging data are illuminating who is at highest risk of developing t-MN, why t-MN are chemoresistant and how we may use this information to treat and ultimately prevent this lethal disease...
August 24, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28713749/mucormycosis-of-the-frontal-sinus-a-rare-case-report-and-review
#6
Nanda Kishore Sahoo, Vishal Kulkarni, Amit K Bhandari, Arun Kumar
Mucormycosis of the frontal sinus are rarely seen in day to day clinical practice. Although this fungus is commonly found in the environment, the disease is usually prevented by the immune system and is hence rare. Well-recognized risk factors for the disease include diabetes mellitus, leukemia, aplastic anemia, myelodysplastic syndrome, blood dyscrasias, and immunosuppressive therapy in organ transplantation, renal disease, sepsis, and severe burns. The disease is primarily found in those who are immunocompromised, but it may also manifest in immuno competent persons...
January 2017: Annals of Maxillofacial Surgery
https://www.readbyqxmd.com/read/28596252/success-in-bone-marrow-failure-novel-therapeutic-directions-based-on-the-immune-environment-of-myelodysplastic-syndromes
#7
REVIEW
Alyssa H Cull, Michael J Rauh
Myelodysplastic syndromes (MDS) are clonal neoplasms of aging that are associated with BM failure, related cytopenias, fatigue, susceptibility to infections, bruising, bleeding, a shortened lifespan, and a propensity for leukemic transformation. Most frail, elderly patients are not candidates for curative allogeneic BM transplantations and instead receive expectant management, supportive blood transfusions, or empirical, nontargeted therapy. It has been known for some time that MDS arises in an abnormal BM immune environment; however, connections have only recently been established with recurring MDS-associated mutations...
August 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28159735/the-microenvironment-in-human-myeloid-malignancies-emerging-concepts-and-therapeutic-implications
#8
REVIEW
Hind Medyouf
Similar to their healthy counterpart, malignant hematopoietic stem cells in myeloid malignancies, such as myeloproliferative neoplasms, myelodysplastic syndromes, and acute myeloid leukemia, reside in a highly complex and dynamic cellular microenvironment in the bone marrow. This environment provides key regulatory signals for and tightly controls cardinal features of hematopoietic stem cells (HSCs), including self-renewal, quiescence, differentiation, and migration. These features are essential to maintaining cellular homeostasis and blood regeneration throughout life...
March 23, 2017: Blood
https://www.readbyqxmd.com/read/27933342/prediction-of-nk-cell-licensing-level-in-selection-of-hematopoietic-stem-cell-donor-initial-results
#9
Marta Rogatko-Koroś, Renata Mika-Witkowska, Katarzyna Bogunia-Kubik, Barbara Wysoczańska, Emilia Jaskuła, Katarzyna Kościńska, Klaudia Nestorowicz, Joanna Dziopa, Urszula Szlendak, Sławomir Gwozdowicz, Elżbieta Graczyk-Pol, Andrzej Lange, Jacek Nowak
Natural killer (NK) cell licensing status depends on clonal expression of inhibitory killer cell immunoglobulin-like receptors (iKIR) and short term HLA environment. Licensed NK cells are more efficient in tumor killing than unlicensed NK cells. Cognate KIR-HLA pairs in hematopoietic stem cell transplant (HSCT) donor and recipient are decisive for the possible change in the NK cell licensing status after HSCT. We assessed clinical outcomes in 297 patients with lymphoproliferative or myeloproliferative malignancies, or myelodysplastic syndrome in a model with upward licensing, downward resetting, and unchanged licensing genetics status after T cell replate HSCT from unrelated donors...
December 2016: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/27313483/development-of-paroxysmal-nocturnal-hemoglobinuria-in-calr-positive-myeloproliferative-neoplasm
#10
Yarden S Fraiman, Nathan Cuka, Denise Batista, Milena Vuica-Ross, Alison R Moliterno
Paroxysmal nocturnal hemoglobinuria (PNH), a disease characterized by intravascular hemolysis, thrombosis, and bone marrow failure, is associated with mutations in the PIG-A gene, resulting in a deficiency of glycosylphosphatidylinositol-anchored proteins. Many hypotheses have been posed as to whether PNH and PIG-A mutations result in an intrinsic survival benefit of CD55(-)/CD59(-) cells or an extrinsic permissive environment that allows for their clonal expansion within the bone marrow compartment. Recent data have identified the concurrence of PIG-A mutations with additional genetic mutations associated with myeloproliferative disorders, suggesting that some presentations of PNH are the result of a stepwise progression of genetic mutations similar to other myelodysplastic or myeloproliferative syndromes...
2016: Journal of Blood Medicine
https://www.readbyqxmd.com/read/27141707/tropical-pyomyositis-in-a-temperate-climate
#11
Sarah Adams, Chelsey Petz
In conclusion, our case highlights the unusual presentation of tropical pyomyositis in a temperate environment. It is important to consider this diagnosis in immunocompromised hosts, even in those with vague complaints such as muscle pain or erythema. The patient's immunocompromised state as well as the rarity of tropical pyomyositis outside of a tropical country led to a late diagnosis. Tropical pyomyositis is a potentially life threatening disease, but if recognized and treated early, the prognosis is good...
December 2015: Journal of the South Carolina Medical Association
https://www.readbyqxmd.com/read/27100058/the-risk-of-infections-in-patients-with-myelodysplastic-syndromes-in-2016
#12
REVIEW
Morena Caira, Roberto Latagliata, Corrado Girmenia
INTRODUCTION: The medical treatment of patients suffering from myelodysplastic syndromes has significantly changed during the last ten years, and this may have impacted the epidemiology of infectious complications. Some 'real world' experiences raised the issue of infections in this setting and the possible negative consequences for patients and health system: the higher the rate of hospitalizations and need for anti-infective therapies, the higher the treatment delays/withdrawal and consecutive the worse the outcome...
June 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27098194/impact-of-socioeconomic-status-on-disease-phenotype-genomic-landscape-and-outcomes-in-myelodysplastic-syndromes
#13
Francesca Mastaglio, Khaled Bedair, Elli Papaemmanuil, Michael J Groves, Ann Hyslop, Norene Keenan, Eleanor J Hothersall, Peter J Campbell, David T Bowen, Sudhir Tauro
Genetic and epigenetic alterations contribute to the biological and clinical characteristics of myelodysplastic syndromes (MDS), but a role for socioeconomic environment remains unclear. Here, socioeconomic status (SES) for 283 MDS patients was estimated using the Scottish Index of Multiple Deprivation tool. Indices were assigned to quintile categorical indicators ranked from SES1 (lowest) to SES5 (highest). Clinicopathological features and outcomes between SES quintiles containing 15%, 20%, 19%, 30% and 16% of patients were compared...
July 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27084249/clinical-significance-of-acquired-somatic-mutations-in-aplastic-anaemia
#14
REVIEW
J C W Marsh, G J Mufti
Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia...
August 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/26708914/-research-advances-on-pathogenesis-of-myelodysplastic-syndrome
#15
REVIEW
Ming Xu, Jia-Hui Lu
Myelodysplastic syndrome (MDS) is a clonal marrow stem cell disorder, characterized by ineffective haemopoiesis leading to blood cytopenias. As a disease of grey zone, along with the development of research, the exploration on its pathogenesis have been shifted from molecular genetics and the feature of immunophenotype to the epigenetic and micro environment. But at present, the pathogenesis of MDS is still not clear, the research of the molecular genetics and immunophenotype can not meet the needs of experimental and clinical application any longer...
December 2015: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/26637737/the-shadowlands-of-mds-idiopathic-cytopenias-of-undetermined-significance-icus-and-clonal-hematopoiesis-of-indeterminate-potential-chip
#16
Luca Malcovati, Mario Cazzola
The WHO classification provides the best diagnostic approach to myelodysplastic syndromes (MDS). However, biologic and analytic limitations have emerged in the criteria currently adopted to establish the diagnosis and to classify MDS. The provisional category of idiopathic cytopenia of undetermined significance (ICUS) has been proposed to describe patients in whom MDS is possible but not proven. To formulate a diagnosis of ICUS, a thorough diagnostic work-up is required and repeated tests should be performed to reach a conclusive diagnosis...
2015: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/26275273/brevundimonas-diminuta-bacteremia-in-a-man-with-myelodysplastic-syndromes
#17
Huiling Cao, Min Li, Xuewen Yang, Chunbing Zhang
Brevundimonas diminuta are ubiquitous in the environment, but are infrequently isolated from clinical samples. Here we report a case of B. diminuta bacteremia in a man with myelodysplastic syndromes (MDS) at a teaching hospital in China and review the previously reported cases. The organism was confirmed by culture and 16s rRNA sequence analysis with highly sensitivity to broad-spectrum antibiotics. Our report and other cases demonstrated that the optimal therapeutic duration for B. diminuta infections in various situations remains to be established...
July 2015: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/26132940/somatic-mutations-and-clonal-hematopoiesis-in-aplastic-anemia
#18
Tetsuichi Yoshizato, Bogdan Dumitriu, Kohei Hosokawa, Hideki Makishima, Kenichi Yoshida, Danielle Townsley, Aiko Sato-Otsubo, Yusuke Sato, Delong Liu, Hiromichi Suzuki, Colin O Wu, Yuichi Shiraishi, Michael J Clemente, Keisuke Kataoka, Yusuke Shiozawa, Yusuke Okuno, Kenichi Chiba, Hiroko Tanaka, Yasunobu Nagata, Takamasa Katagiri, Ayana Kon, Masashi Sanada, Phillip Scheinberg, Satoru Miyano, Jaroslaw P Maciejewski, Shinji Nakao, Neal S Young, Seishi Ogawa
BACKGROUND: In patients with acquired aplastic anemia, destruction of hematopoietic cells by the immune system leads to pancytopenia. Patients have a response to immunosuppressive therapy, but myelodysplastic syndromes and acute myeloid leukemia develop in about 15% of the patients, usually many months to years after the diagnosis of aplastic anemia. METHODS: We performed next-generation sequencing and array-based karyotyping using 668 blood samples obtained from 439 patients with aplastic anemia...
July 2, 2015: New England Journal of Medicine
https://www.readbyqxmd.com/read/25695174/in-hospital-transfer-is-a-risk-factor-for-invasive-filamentous-fungal-infection-among-hospitalized-patients-with-hematological-malignancies-a-matched-case-control-study
#19
Angèle Gayet-Ageron, Anne Iten, Christian van Delden, Natacha Farquet, Stavroula Masouridi-Levrat, Elodie Von Dach, Yves Chalandon, Didier Pittet
OBJECTIVE: Immunocompromised patients now benefit from a longer life expectancy due to advanced medical techniques, but they are also weakened by aggressive treatment approaches and are at high risk for invasive fungal disease. We determined risk factors associated with an outbreak of invasive filamentous fungal infection (IFFI) among hospitalized hemato-oncological patients. METHODS: A retrospective, matched, case-control study was conducted between January 1, 2009, and April 31, 2011, including 29 cases (6 proven, 8 probable, and 15 possible) of IFFI and 102 matched control patients hospitalized during the same time period...
March 2015: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/25679997/despite-differential-gene-expression-profiles-pediatric-mds-derived-mesenchymal-stromal-cells-display-functionality-in-vitro
#20
F G J Calkoen, C Vervat, M van Pel, V de Haas, L S Vijfhuizen, E Eising, W G M Kroes, P A C 't Hoen, M M van den Heuvel-Eibrink, R M Egeler, M J D van Tol, L M Ball
Pediatric myelodysplastic syndrome (MDS) is a heterogeneous disease covering a spectrum ranging from aplasia (RCC) to myeloproliferation (RAEB(t)). In adult-type MDS there is increasing evidence for abnormal function of the bone-marrow microenvironment. Here, we extensively studied the mesenchymal stromal cells (MSCs) derived from children with MDS. MSCs were expanded from the bone-marrow of 17 MDS patients (RCC: n=10 and advanced MDS: n=7) and pediatric controls (n=10). No differences were observed with respect to phenotype, differentiation capacity, immunomodulatory capacity or hematopoietic support...
March 2015: Stem Cell Research
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