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Myelodysplasia

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https://www.readbyqxmd.com/read/29930011/impact-of-spliceosome-mutations-on-rna-splicing-in-myelodysplasia-dysregulated-genes-pathways-and-clinical-associations
#1
Andrea Pellagatti, Richard N Armstrong, Violetta Steeples, Eshita Sharma, Emmanouela Repapi, Shalini Singh, Andrea Sanchi, Aleksandar Radujkovic, Patrick Horn, Hamid Dolatshad, Swagata Roy, John Broxholme, Helen Lockstone, Stephen Taylor, Aristoteles Giagounidis, Paresh Vyas, Anna Schuh, Angela Hamblin, Elli Papaemmanuil, Sally Killick, Luca Malcovati, Marco L Hennrich, Anne-Claude Gavin, Anthony D Ho, Thomas Luft, Eva Hellström-Lindberg, Mario Cazzola, Christopher W J Smith, Stephen Smith, Jacqueline Boultwood
SF3B1, SRSF2 and U2AF1 are the most frequently mutated splicing factor genes in the myelodysplastic syndromes (MDS). We have performed a comprehensive and systematic analysis to determine the impact of these commonly mutated splicing factors on pre-mRNA splicing in the bone marrow stem/progenitor cells and in the erythroid and myeloid precursors in splicing factor mutant MDS. Using RNA-seq, we determined the aberrantly spliced genes and dysregulated pathways in CD34+ cells of 84 MDS patients. Splicing factor mutations result in different alterations in splicing and largely affect different genes, but these converge in common dysregulated pathways and cellular processes, focused on RNA splicing, protein synthesis and mitochondrial dysfunction, suggesting common mechanisms of action in MDS...
June 21, 2018: Blood
https://www.readbyqxmd.com/read/29928134/reformulating-acute-myeloid-leukemia-liposomal-cytarabine-and-daunorubicin-cpx-351-as-an-emerging-therapy-for-secondary-aml
#2
REVIEW
Evan C Chen, Amir T Fathi, Andrew M Brunner
Despite increasing understanding of the pathobiology of acute myeloid leukemia (AML), outcomes remain dismal particularly for patients over the age of 60 years, a population enriched for therapy-related AML (tAML) and secondary AML (sAML). For decades, the standard of care for AML has been the combination of cytarabine and daunorubicin, typically delivered in combination as "7 + 3" induction. In 2017, a liposomal-encapsulated combination of daunorubicin and cytarabine (CPX-351, Vyxeos) was approved by the US Food and Drug Administration (FDA) for use in the treatment of newly diagnosed tAML or AML with myelodysplasia-related changes (AML-MRCs)...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29922299/the-emerging-link-between-the-complement-cascade-and-purinergic-signaling-in-stress-hematopoiesis
#3
REVIEW
Mariusz Z Ratajczak, Mateusz Adamiak, Magda Kucia, William Tse, Janina Ratajczak, Wieslaw Wiktor-Jedrzejczak
Innate immunity plays an important role in orchestrating the immune response, and the complement cascade (ComC) is a major component of this ancient defense system, which is activated by the classical-, alternative-, or mannan-binding lectin (MBL) pathways. However, the MBL-dependent ComC-activation pathway has been somewhat underappreciated for many years; recent evidence indicates that it plays a crucial role in regulating the trafficking of hematopoietic stem/progenitor cells (HSPCs) by promoting their egress from bone marrow (BM) into peripheral blood (PB)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29915954/impact-of-patient-position-on-coronal-cobb-angle-measurement-in-non-ambulatory-myelodysplastic-patients
#4
Norman Ramirez, Jorge Padilla, Sigfredo Villarin, Francisco Irizarry, Ivan Iriarte, Jeffrey Sawyer
OBJECTIVE: The purpose of this study was to assess the impact of patient position on the magnitude of the coronal Cobb angle measurements in relation to the change of position using plain radiograph on non-ambulatory children with myelodysplasia. Whole-spine radiographs with the patient sitting generally are preferred for the diagnosis and monitoring of progression of scoliosis in neuromuscular patients. Supine, supine traction, and sitting push-up positions have been used as substitutes, although there is no general consensus validating if these positions correlate with the sitting position...
June 18, 2018: European Journal of Orthopaedic Surgery & Traumatology: Orthopédie Traumatologie
https://www.readbyqxmd.com/read/29878897/prdm16-isoforms-differentially-regulate-normal-and-leukemic-hematopoiesis-and-inflammatory-gene-signature
#5
David J Corrigan, Larry L Luchsinger, Mariana Justino de Almeida, Linda J Williams, Alexandros Strikoudis, Hans-Willem Snoeck
PRDM16 is a transcriptional co-regulator involved in translocations in acute myeloblastic leukemia (AML), myelodysplastic syndromes and T acute lymphoblastic leukemia that is highly expressed in and required for the maintenance of hematopoietic stem cells (HSCs), and can be aberrantly expressed in AML. Prdm16 is expressed as full-length (fPrdm16) and short (sPrdm16) isoforms, the latter lacking the N-terminal PR-domain. The role of both isoforms in normal and malignant hematopoiesis is unclear. We show here that fPrdm16 was critical for HSC maintenance, induced multiple genes involved in GTPase signaling and repressed inflammation, while sPrdm16 supported B-cell development biased towards marginal zone B-cells and induced an inflammatory signature...
June 7, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29877282/invasive-pulmonary-aspergillosis-in-the-epidural-space-in-a-patient-with-acute-myelogenous-leukemia-with-myelodysplasia-related-changes-a-case-study-and-literature-review-of-vertebral-aspergillosis-in-japan
#6
Ryohei Ono, Shuku Sato, Satomi Okada, Emiko Kanbe, Eri Tanaka, Yotaro Tamai
Vertebral aspergillosis is a rare infectious disease with a high mortality rate. We herein report a 70-year-old woman with acute myelogenous leukemia with myelodysplasia-related changes, nontuberculous mycobacteriosis, and bronchiectasis who presented with a fever and cough. Her clinical symptoms and laboratory test results suggested febrile neutropenia and pneumonia. However, her clinical course was further complicated by lower extremity weakness. Magnetic resonance imaging of the spine showed consolidation contiguously spreading toward the epidural space between the T4 and T5...
June 6, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29874133/risk-risk-factors-and-surveillance-of-subsequent-malignant-neoplasms-in-survivors-of-childhood-cancer-a-review
#7
Lucie M Turcotte, Joseph P Neglia, Raoul C Reulen, Cecile M Ronckers, Flora E van Leeuwen, Lindsay M Morton, David C Hodgson, Yutaka Yasui, Kevin C Oeffinger, Tara O Henderson
Subsequent malignant neoplasms (SMNs) in childhood cancer survivors cause substantial morbidity and mortality. This review summarizes recent literature on SMN epidemiology, risk factors, surveillance, and interventions. Survivors of childhood cancer experience long-term increased SMN risk compared with the general population, with a greater than twofold increased solid tumor risk extending beyond age 40 years. There is a dose-dependent increased risk for solid tumors after radiotherapy, with the highest risks for tumors occurring in or near the treatment field (eg, greater than fivefold increased risk for breast, brain, thyroid, skin, bone, and soft tissue malignancies)...
June 6, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29799854/phenotypic-characterization-of-aberrant-stem-and-progenitor-cell-populations-in-myelodysplastic-syndromes
#8
Benjamin N Ostendorf, Eva Flenner, Anne Flörcken, Jörg Westermann
Recent reports have revealed myelodysplastic syndromes (MDS) to arise from cancer stem cells phenotypically similar to physiological hematopoietic stem cells. Myelodysplastic hematopoiesis maintains a hierarchical organization, but the proportion of several hematopoietic compartments is skewed and multiple surface markers are aberrantly expressed. These aberrant antigen expression patterns hold diagnostic and therapeutic promise. However, eradication of MDS requires targeting of early myelodysplasia propagating stem cells...
2018: PloS One
https://www.readbyqxmd.com/read/29795414/risk-of-subsequent-myeloid-neoplasms-after-radiotherapy-treatment-for-a-solid-cancer-among-adults-in-the-united-states-2000-2014
#9
Jop C Teepen, Rochelle E Curtis, Graça M Dores, Amy Berrington de Gonzalez, Marry M van den Heuvel-Eibrink, Leontien C M Kremer, Ethel S Gilbert, Flora E van Leeuwen, Cécile M Ronckers, Lindsay M Morton
Although increased risk of acute myeloid leukemia (AML) has been observed after chemotherapy and radiotherapy, less is known about radiotherapy-related risks of specific AML subtypes and other specific myeloid neoplasms. We used the US population-based cancer registry data to evaluate risk of myeloid neoplasms among three cohorts of cancer survivors initially treated with radiotherapy only. We included 1-year survivors of first primary thyroid (radioiodine only, stages I-IV; N = 49 879), prostate (excluding stage IV; N = 237 439), or uterine corpus cancers (stage I-II; N = 16 208) diagnosed during 2000-2013...
May 24, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29795094/-chronic-sacral-nerve-electrostimulation-in-treatment-of-neurogenic-pelvic-organ-dysfunction-in-children
#10
A V Dekopov, A A Tomskiy, R V Salyukov, Yu R Salyukova, O E Machevskaya, Sh U Kadyrov
Myelodysplasia is the most common cause of congenital pelvic abnormalities in children. The causes of acquired neurogenic pelvic dysfunctions in children include spinal cord injury, myelitis, and neurodegenerative diseases. Urination impairments in children with neurological disorders are a serious clinical problem. In most cases, the capabilities of conservative treatment of pelvic organ dysfunctions are limited. One of the most promising directions in treatment of neurogenic urination disorders is modeling of a lost urination mechanism using direct or mediated electrostimulation of the nerve fibers of the sacral plexus - neuromodulation...
2018: Zhurnal Voprosy Neĭrokhirurgii Imeni N. N. Burdenko
https://www.readbyqxmd.com/read/29785506/venetoclax-and-low-dose-cytarabine-induced-complete-remission-in-a-patient-with-high-risk-acute-myeloid-leukemia-a-case-report
#11
Bingshan Liu, Roshni Narurkar, Madhura Hanmantgad, Wahib Zafar, Yongping Song, Delong Liu
Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. Venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway...
May 21, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29770900/insights-into-mutation-effect-in-three-poikiloderma-with-neutropenia-patients-by-transcript-analysis-and-disease-evolution-of-reported-patients-with-the-same-pathogenic-variants
#12
Elisa A Colombo, Nursel H Elcioglu, Claudio Graziano, Pamela Farinelli, Elisabetta Di Fede, Iria Neri, Elena Facchini, Mariangela Greco, Cristina Gervasini, Lidia Larizza
PURPOSE: Poikiloderma with neutropenia (PN) is a genodermatosis currently described in 77 patients, all presenting with early-onset poikiloderma, neutropenia, and several additional signs. Biallelic loss-of-function mutations in USB1 gene are detected in all molecularly tested patients but genotype-phenotype correlation remains elusive. Cancer predisposition is recognized among PN features and pathogenic variants found in patients who developed early in life myelodysplasia (n = 12), acute myeloid leukemia (n = 2), and squamous cell carcinoma (n = 2) should be kept into account in management and follow-up of novel patients...
May 16, 2018: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29769208/infusion-of-alloanergized-donor-lymphocytes-after-cd34-selected-haploidentical-myeloablative-hematopoietic-stem-cell-transplantation
#13
Jeff K Davies, Lisa L Brennan, John Wingard, Christopher R Cogle, Neena Kapoor, Ami J Shah, Bimalangshu R Dey, Thomas R Spitzer, Marcos De Lima, Laurence Jn Cooper, Peter Thall, Richard E Champlin, Lee M Nadler, Eva C Guinan
PURPOSE: Allogeneic haematopoietic stem-cell transplantation (HSCT) is a curative treatment for many haematologic cancers. Use of haploidentical (mismatched) donors increases HSCT availability but is limited by severe graft-versus-host disease (GvHD) and delayed immune reconstitution. Alloanergization of donor T-cells is a simple approach to rebuild immunity whilst limiting GvHD after haploidentical HSCT but the optimal T-cell dose and impact on immune reconstitution remain unknown.  Experimental Design: We performed a multicentre Phase 1 trial of alloanergized donor lymphocyte infusion (aDLI) after CD34-selected myeloablative haploidentical HSCT...
May 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29742616/spontaneous-remission-of-monosomy-7-six-years-after-diagnosis
#14
Holly J Edington, Eric J Lowe
Monosomy 7 may be a poor prognostic indicator in pediatric myelodysplastic syndrome. There are case reports of children with monosomy 7 who undergo spontaneous remission 2 to 24 months after diagnosis. We report a case of a child with bone marrow failure and monosomy 7 who underwent spontaneous remission 75 months after diagnosis. The patient had no exposure to chemotherapeutic or immunosuppressive agents. The patient did not receive chemotherapy or other treatment during the 75 months. Despite remaining positive for monosomy 7, he never developed myelodysplasia or acute myeloid leukemia...
May 8, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29741254/present-status-and-perspective-of-laboratory-hematology-in-japan-on-the-standardization-of-blood-cell-morphology-including-myelodysplasia-on-behalf-of-the-japanese-society-for-laboratory-hematology
#15
REVIEW
K Tohyama
The Japanese Society for Laboratory Hematology (JSLH) was launched in 2000 and has been developed by a mutual collaboration of hematologists, medical technologists, and the companies involved in hematological laboratory testing. The aim of JSLH is the progress and development of laboratory hematology by academic conferences, periodic publication of academic journal, training and education (in the meeting, the journal, or the website), promotion of the standardization of laboratory hematology, and certification of the laboratory hematology specialists...
May 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29723094/power-of-absolute-values-to-avoid-data-misinterpretations-the-case-of-radioiodine-induced-leukemia-and-myelodysplasia
#16
Arnoldo Piccardo, Matteo Puntoni, Frederik A Verburg, Markus Luster, Luca Giovanella
No abstract text is available yet for this article.
June 20, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29712663/a-population-pharmacokinetic-model-for-a-solid-oral-tablet-formulation-of-posaconazole
#17
Marlou L P S van Iersel, Stefaan Rossenu, Rik de Greef, Hetty Waskin
A delayed-release solid tablet formulation that releases posaconazole in the small intestine was developed to maximize systemic absorption. This study aimed to characterize the pharmacokinetics of the posaconazole solid tablet formulation in adult subjects and to investigate the potential impact of demographic and clinical factors on posaconazole exposure through a population pharmacokinetic approach. Nonlinear mixed-effects modeling was performed using data from several studies conducted in healthy volunteers and patients...
April 30, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29672642/runx1-pdcd6-fusion-resulting-from-a-novel-t-5-21-p15-q22-chromosome-translocation-in-myelodysplastic-syndrome-secondary-to-chronic-lymphocytic-leukemia
#18
Ioannis Panagopoulos, Ludmila Gorunova, Eva-Marie Jacobsen, Kristin Andersen, Francesca Micci, Sverre Heim
Leukemic cells often carry chromosome aberrations which generate chimeric genes of pathogenetic, diagnostic, and prognostic importance. New rearrangements giving rise to novel fusion genes define hitherto unrecognized genetic leukemia subgroups. G-banding, fluorescence in situ hybridization (FISH), and molecular genetic analyses were done on bone marrow cells from a patient with chronic lymphocytic leukemia (CLL) and secondary myelodysplasia. The G-banding analysis revealed the karyotype 46,XX,del(21)(q22)[9]/46,XX[2]...
2018: PloS One
https://www.readbyqxmd.com/read/29668470/secondary-hodgkin-lymphoma-and-myelodysplastic-syndrome-mds-after-paclitaxel-carboplatin-treatment-in-a-patient-with-small-cell-lung-cancer
#19
Marija Petrusevska, Irina Panovska Stavridis, Kristina Mladenovska, Gordana Petrushevska
Herein synchronous occurrence of Hodgkin lymphoma and secondary myelodysplastic syndrome in a 60 year old male patient with small cell lung cancer treated with combined chemotherapy (carboplatin and paclitaxel) and radiotherapy is presented. The objective of this report is to stress the importance of documenting and monitoring adverse drug reactions that arise from chemotherapy. After four years of treatment with the combined chemotherapy, the patient presented inguinal lymphadenopathy and enlarged lymph nodes and histopathology rapport was suggestive for plasmacytoid variant of Castleman disease...
December 1, 2017: Prilozi (Makedonska Akademija Na Naukite i Umetnostite. Oddelenie za Medicinski Nauki)
https://www.readbyqxmd.com/read/29653202/clinicopathological-features-and-outcomes-of-pythiosis
#20
Maria Nina Chitasombat, Noppadol Larbcharoensub, Ariya Chindamporn, Theerapong Krajaejun
OBJECTIVES: Vascular pythiosis is a life-threatening infection caused by the oomycete Pythium insidiosum. This article reports the clinical presentation, serodiagnosis, pathology, and outcomes seen at the authors' institution. METHODS: The cases of patients with proven vascular pythiosis at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand from January 2006 to December 2016 were analyzed retrospectively. RESULTS: Thirteen patients were analyzed, eight of whom had underlying thalassemias...
June 2018: International Journal of Infectious Diseases: IJID
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