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https://www.readbyqxmd.com/read/29791902/the-molecular-pathology-of-myelodysplastic-syndrome
#1
Torsten Haferlach
The diagnosis and classification of myelodysplastic syndromes (MDS) are based on cytomorphology and cytogenetics (WHO classification). Prognosis is best defined by the Revised International Prognostic Scoring System (IPSS-R). In recent years, an increasing number of molecular aberrations have been discovered. They are already included in the classification (e.g., SF3B1) and, more importantly, have emerged as valuable markers for better classification, particularly for defining risk groups. Mutations in genes such as SF3B1 and IDH1/2 have already had an impact on targeted treatment approaches in MDS...
May 23, 2018: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29789885/instability-of-endosperm-development-in-amphiploids-and-their-parental-species-in-the-genus-avena-l
#2
Paulina Tomaszewska, Romuald Kosina
The development of oat endosperm is modified by chromatin and nuclei elimination, intrusive growth of cell walls, and polyploidisation of cell clones. The last event is correlated with somatic crossing-over. Grass endosperm is a variable tissue in terms of its cytogenetics and development. Free-nuclear syncytium and starchy and aleurone endosperm were the main focus of the research. These were studied in oat amphiploids (4x, 6x, and 8x) and parental species (2x, 4x, and 6x). What the levels of cytogenetic disorders and developmental anomalies in species versus hybrids are, and, what the factors are determining phenotypes of both tissue components, are open questions for oats...
May 22, 2018: Plant Cell Reports
https://www.readbyqxmd.com/read/29789356/risk-adapted-treatment-of-acute-promyelocytic-leukemia-results-from-international-consortium-for-childhood-apl
#3
Anna Maria Testi, Andrea Pession, Daniela Diverio, David Grimwade, Brenda Gibson, Amilcar Cardoso de Azevedo, Lorena Moran, Guy Leverger, Sarah Elitzur, Henrik Hasle, Jutte van der Werff Ten Bosch, Owen Smith, Marisa De Rosa, Alfonso Piciocchi, Francesco Lo Coco, Robin Foà, Franco Locatelli, Gertjan J L Kaspers
Pediatric acute promyelocytic leukemia (APL), a rare childhood neoplasm, can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials to date have employed high cumulative doses of anthracyclines. Here, we report the outcome of patients with newly diagnosed APL enrolled into the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically-proven APL...
May 22, 2018: Blood
https://www.readbyqxmd.com/read/29787441/exome-sequencing-discloses-ionizing-radiation-induced-dna-variants-in-the-genome-of-human-gingiva-fibroblasts
#4
Neetika Nath, Jennifer Esche, Jessica Müller, Lars R Jensen, Matthias Port, Mario Stanke, Lars Kaderali, Harry Scherthan, Andreas W Kuss
Ionizing radiation can induce genomic lesions such as DNA double-strand breaks whose incomplete or faulty repair can result in mutations, which in turn can influence cellular functions and alter the fate of affected cells and organ systems. Ionizing-radiation-induced sequence alterations/mutations occur in a stochastic manner, which contributes to an increased cancer risk in irradiated individuals. Ionizing radiation exposure, and particularly acute doses at high dose rates (as often observed in radiation accidents), induce alterations in the genome that in part will reflect specific characteristics of the DNA damage response and the repair mechanisms involved...
July 2018: Health Physics
https://www.readbyqxmd.com/read/29787320/gemtuzumab-ozogamicin-for-the-treatment-of-acute-myeloid-leukemia
#5
Jeffrey Baron, Eunice S Wang
Gemtuzumab ozogamicin (GO) is an antibody-drug conjugate consisting of a monoclonal antibody targeting CD33 linked to a cytotoxic derivative of calicheamicin. Despite the known clinical efficacy in relapsed/refractory acute myeloid leukemia (AML), GO was withdrawn from the market in 2010 due to increased early deaths seen in newly diagnosed AML patients receiving GO + intensive chemotherapy. In 2017, new data on the clinical efficacy and safety of GO administered on a fractionated dosing schedule led to re-approval for newly diagnosed and relapsed/refractory AML...
May 22, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29785311/acute-lymphoblastic-leukemia-following-lenalidomide-maintenance-for-multiple-myeloma-two-cases-with-unexpected-presentation-and-good-prognostic-features
#6
Abdullah M Khan, Jameel Muzaffar, Hermant Murthy, John R Wingard, Jan S Moreb
Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29784931/reconstruction-of-the-diapsid-ancestral-genome-permits-chromosome-evolution-tracing-in-avian-and-non-avian-dinosaurs
#7
Rebecca E O'Connor, Michael N Romanov, Lucas G Kiazim, Paul M Barrett, Marta Farré, Joana Damas, Malcolm Ferguson-Smith, Nicole Valenzuela, Denis M Larkin, Darren K Griffin
Genomic organisation of extinct lineages can be inferred from extant chromosome-level genome assemblies. Here, we apply bioinformatic and molecular cytogenetic approaches to determine the genomic structure of the diapsid common ancestor. We then infer the events that likely occurred along this lineage from theropod dinosaurs through to modern birds. Our results suggest that most elements of a typical 'avian-like' karyotype (40 chromosome pairs, including 30 microchromosomes) were in place before the divergence of turtles from birds ~255 mya...
May 21, 2018: Nature Communications
https://www.readbyqxmd.com/read/29784749/prognostic-significance-of-molecular-markers-and-targeted-regimens-in-the-management-of-acute-myeloid-leukemia
#8
Martin Tallman
The diagnosis, staging, and treatment of acute myeloid leukemia (AML) has evolved based on identification of important genetic alterations and drugs to target those genes. Cytogenetic abnormalities play a major role in managing AML. Achieving minimal residual disease is an increasingly important milestone. Four new targeted therapies are now available for the treatment of AML.
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784748/emerging-treatment-options-for-acute-lymphoblastic-leukemia-focus-on-car-t-cell-therapy
#9
Patrick A Brown, Bijal Shah
Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of diseases with different morphologic, cytogenetic, and molecular subgroups, some of which have significant therapeutic implications. It typically presents with an aggressive clinical course, and among adults, responds poorly to standard chemotherapy, and carries a high risk for relapse. Despite the significant progress made in inducing remission, frequent relapses remain a challenge. Novel drugs, such as potent later-generation tyrosine kinase inhibitors, antibody-drug conjugates, bispecific monoclonal antibodies, and chimeric antigen receptor (CAR) T-cell therapies, are being investigated in patients with ALL...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784741/management-of-multiple-myeloma
#10
Shaji K Kumar
The most recent NCCN Guidelines for Multiple Myeloma include a ranking of the many treatment options for various settings as "preferred," "other," and "useful in certain circumstances." For patients eligible for autologous stem cell transplant (ASCT), the preferred regimen remains bortezomib/lenalidomide/dexamethasone (category 1) or bortezomib/cyclophosphamide/dexamethasone. Upfront ASCT also remains a preferred strategy for patients who are transplant-eligible, despite highly effective newer agents such as induction therapy...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29780444/karyotype-description-and-comparative-analysis-in-ringed-kingfisher-and-green-kingfisher-coraciiformes-alcedinidae
#11
Tiago Marafiga Degrandi, Jean Carlo Pedroso de Oliveira, Amanda de Araújo Soares, Mario Angel Ledesma, Iris Hass, Analía Del Valle Garnero, Ricardo José Gunski
Kingfishers comprise about 115 species of the family Alcedinidae, and are an interesting group for cytogenetic studies, for they are among birds with most heterogeneous karyotypes. However, cytogenetics knowledge in Kingfishers is extremely limited. Thus, the aim of this study was to describe the karyotype structure of the Ringed Kingfisher ( Megaceryle torquata Linnaeus, 1766) and Green Kingfisher ( Chloroceryle americana Gmelin, 1788) and also compare them with related species in order to identify chromosomal rearrangements...
2018: Comparative Cytogenetics
https://www.readbyqxmd.com/read/29779352/-effect-of-1q21-amplification-on-bortezomib-therapeutic-response-and-prognosis-of-newly-diagnosed-multiple-myeloma-patients
#12
X L Liu, P Y Yang, X Y Yu, J C Chen, X L Liu, J Bai, Y M Liu, H He, J N Sun, H Q Fan, C Zhang, Y Zhang, K J Su, C S Liu, Y H Tan, S J Gao, W Li, F Y Jin
Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51...
May 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29779345/-role-of-minimal-residual-disease-detection-by-multiparameter-flow-cytometry-in-newly-diagnosed-multiple-myeloma-an-analysis-of-106-patients
#13
S H Deng, Y Xu, W W Sui, H J Wang, Z J Li, T Y Wang, W Liu, W Y Huang, R Lyu, J Li, M W Fu, D H Zou, G An, L G Qiu
Objective: To assess the feasibility and prognostic value of the minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in the newly diagnosed multiple myeloma (MM) patients of China. Methods: Clinical data of 106 consecutively newly diagnosed MM patients with MRD data were retrospectively analyzed in a single center in China from June 2013 to June 2015. Results: ① Of 106 patients, 48 (45.3%) achieved MRD negativity. The median time to MRD-negative was 3 months. More patients undergoing autologous stem cell transplantation (ASCT) achieved MRD negativity compared with non-ASCT patients (62...
May 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29776991/inversion-variants-in-human-and-primate-genomes
#14
Claudia Rita Catacchio, Flavia Angela Maria Maggiolini, Pietro D'Addabbo, Miriana Bitonto, Oronzo Capozzi, Martina Lepore Signorile, Mattia Miroballo, Nicoletta Archidiacono, Evan E Eichler, Mario Ventura, Francesca Antonacci
For many years, inversions have been proposed to be a direct driving force in speciation since they suppress recombination when heterozygous. Inversions are the most common large-scale differences among humans and great apes. Nevertheless, they represent large events easily distinguishable by classical cytogenetics, whose resolution, however, is limited. Here, we performed a genome-wide comparison between human, great ape, and macaque genomes using the net alignments for the most recent releases of genome assemblies...
May 18, 2018: Genome Research
https://www.readbyqxmd.com/read/29776632/molecular-diagnosis-of-hematopoietic-neoplasms-2018-update
#15
REVIEW
Radhakrishnan Ramchandren, Tarek Jazaerly, Martin H Bluth, Ali M Gabali
Diagnosis of hematologic malignancies have matured to encompass molecular as well as phenotypic characteristics. Cytogenetic abnormalities are considered common events in this regard. These abnormalities generally consist of structural chromosomal abnormalities or gene mutations, which often are integral to the pathogenesis and subsequent evolution of an individual malignancy. Improvements made in identifying and interpreting these molecular alterations have resulted in advances in the diagnosis, prognosis, monitoring, and therapy for cancer...
June 2018: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29775402/a-note-on-poisson-goodness-of-fit-tests-for-ionizing-radiation-induced-chromosomal-aberration-samples
#16
Manuel Higueras, J E González, Marina Di Giorgio, J F Barquinero
PURPOSE: To present Poisson exact goodness-of-fit tests as alternatives and complements to the asymptotic u-test, which is the most widely used in cytogenetic biodosimetry, to decide whether a sample of chromosomal aberrations in blood cells comes from an homogeneous or inhomogeneous exposure. MATERIALS AND METHODS: Three Poisson exact goodness-of-fit test from the literature are introduced and implemented in the R environment. A Shiny R Studio application, named GOF Poisson, has been updated for the purpose of giving support to this work...
May 18, 2018: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29774518/huh-7-reference-genome-profile-complex-karyotype-composed-of-massive-loss-of-heterozygosity
#17
Fumio Kasai, Noriko Hirayama, Midori Ozawa, Motonobu Satoh, Arihiro Kohara
Human cell lines represent a valuable resource as in vitro experimental models. A hepatoma cell line, HuH-7 (JCRB0403), has been used extensively in various research fields and a number of studies using this line have been published continuously since it was established in 1982. However, an accurate genome profile, which can be served as a reliable reference, has not been available. In this study, we performed M-FISH, SNP microarray and amplicon sequencing to characterize the cell line. Single cell analysis of metaphases revealed a high level of heterogeneity with a mode of 60 chromosomes...
May 17, 2018: Human Cell
https://www.readbyqxmd.com/read/29773593/safety-and-efficacy-of-second-line-bosutinib-for-chronic-phase-chronic-myeloid-leukemia-over-a-five-year-period-final-results-of-a-phase-1-2-study
#18
Carlo Gambacorti-Passerini, Jorge E Cortes, Jeff H Lipton, Hagop M Kantarjian, Dong-Wook Kim, Philippe Schafhausen, Rocco Crescenzo, Nathalie Bardy-Bouxin, Mark Shapiro, Kay Noonan, Eric Leip, Liza DeAnnuntis, Tim H Brümmendorf, H Jean Khoury
Bosutinib is a Src/Abl tyrosine kinase inhibitor indicated for adults with newly-diagnosed Ph+ chronic myeloid leukemia or with resistant/intolerant disease. We report the final results of a phase 1/2 study of second-line bosutinib in chronic phase chronic myeloid leukemia patients after imatinib failure (n=284). Median follow-up and treatment durations were 54.8 (range, 0.6-96.3) and 25.6 (0.2&-96.3) months, respectively. At years 2 and 5, 54% and 40% of patients, respectively, remained on bosutinib. Cumulative major cytogenetic response and complete cytogenetic response rates (newly-attained or maintained from baseline) were 58% and 46%, respectively, by year 2 and 60% and 50% by year 5...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29768882/grape-seed-extract-alone-or-combined-with-atropine-in-treatment-of-malathion-induced-neuro-and-genotoxicity
#19
Omar M E Abdel-Salam, Asmaa F Galal, Mahrousa M Hassanane, Lamiaa M Salem, Somaia A Nada, Fatma A Morsy
The aim of this study was to investigate the effect of treatment with grape seed extract (GSE) on the neurotoxic and genotoxic effects of acute malathion exposure. Rats received malathion (150 mg/kg by i.p. injection) for two successive days alone or combined with GSE at doses of 150 or 300 mg/kg, orally or with GSE at 300 mg/kg and atropine at a dose of 2 mg/kg, i.p. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, paraoxonase (PON1) were determined in cortex, striatum, and rest of brain tissue (subcortex)...
January 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29768880/tio%C3%A2-nps-induce-dna-damage-in-lymphocytes-from-healthy-individuals-and-patients-with-respiratory-diseases-an-ex-vivo-in-vitro-study
#20
Ilham F Osman, Mojgan Najafzadeh, Vyom Sharma, Ritesh K Shukla, B K Jacob, Alok Dhawan, D Anderson
Little is known of the effects of nanoparticles in human systems, let alone in diseased individuals and nanotechnology has preceded nanotoxicology. Therefore, the effects of titanium dioxide (TiO2) nanoparticles in peripheral blood lymphocytes from patients with respiratory diseases [lung cancer, chronic obstructive pulmonary disease (COPD) and asthma] were compared with those in healthy Individuals, to determine differences in sensitivity to nanochemical insult. The Comet assay was performed according to recommended guidelines...
January 1, 2018: Journal of Nanoscience and Nanotechnology
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