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https://www.readbyqxmd.com/read/29352719/prognostic-testing-patterns-and-outcomes-of-chronic-lymphocytic-leukemia-patients-stratified-by-fluorescence-in-situ-hybridization-cytogenetics-a-real-world-clinical-experience-in-the-connect-cll-registry
#1
Anthony Mato, Chadi Nabhan, Neil E Kay, Nicole Lamanna, Thomas J Kipps, David L Grinblatt, Christopher R Flowers, Charles M Farber, Matthew S Davids, Pavel Kiselev, Arlene S Swern, Shriya Bhushan, Kristen Sullivan, E Dawn Flick, Jeff P Sharman
INTRODUCTION: Prognostic genetic testing is recommended for patients with chronic lymphocytic leukemia (CLL) to guide clinical management. Specific abnormalities, such as del(17p), del(11q), and unmutated IgHV, can predict the depth and durability of the response to CLL therapy. PATIENTS AND METHODS: In the present analysis of the Connect CLL Registry (ClinicalTrials.gov identifier, NCT01081015), a prospective observational cohort study of patients treated across 199 centers, the patterns of prognostic testing and outcomes of patients with unfavorable-risk genetics were analyzed...
December 6, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29352181/samhd1-is-recurrently-mutated-in-t-cell-prolymphocytic-leukemia
#2
Patricia Johansson, Ludger Klein-Hitpass, Axel Choidas, Peter Habenberger, Bijan Mahboubi, Baek Kim, Anke Bergmann, René Scholtysik, Martina Brauser, Anna Lollies, Reiner Siebert, Thorsten Zenz, Ulrich Dührsen, Ralf Küppers, Jan Dürig
T-cell prolymphocytic leukemia (T-PLL) is an aggressive malignancy with a median survival of the patients of less than two years. Besides characteristic chromosomal translocations, frequent mutations affect the ATM gene, JAK/STAT pathway members, and epigenetic regulators. We here performed a targeted mutation analysis for 40 genes selected from a RNA sequencing of 10 T-PLL in a collection of 28 T-PLL, and an exome analysis of five further cases. Nonsynonymous mutations were identified in 30 of the 40 genes, 18 being recurrently mutated...
January 19, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29352038/microenvironment-induced-cd44v6-promotes-early-disease-progression-in-chronic-lymphocytic-leukemia
#3
Julia C Gutjahr, Eva Szenes, Lisa Tschech, Daniela Asslaber, Michaela Schlederer, Simone Roos, Xiaobing Yu, Tamara Girbl, Christina Sternberg, Alexander Egle, Fritz Aberger, Ronen Alon, Lukas Kenner, Richard Greil, Veronique Orian-Rousseau, Tanja N Hartmann
Chronic lymphocytic leukemia (CLL) outgrowth depends on signals from the microenvironment. We have previously found that in vitro reconstitution of this microenvironment induces specific variant isoforms of the adhesion molecule CD44, which confer human CLL with high affinity to hyaluronan (HA). Here, we determined the in vivo contribution of standard CD44 and its variants to leukemic B-cell homing and proliferation in Tcl1 transgenic mice with a B-cell-specific CD44 deficiency. In these mice, leukemia onset was delayed and leukemic infiltration of spleen, liver, and lungs, but not of bone marrow was decreased...
January 19, 2018: Blood
https://www.readbyqxmd.com/read/29351999/mll1-promotes-il-7-responsiveness-and-survival-during-b-cell-differentiation
#4
Tao Gan, Bin E Li, Bibhu P Mishra, Kenneth L Jones, Patricia Ernst
B lymphocyte differentiation is an exquisitely regulated homeostatic process resulting in continuous production of appropriately selected B cells. Relatively small changes in gene expression can result in deregulation of this process, leading to acute lymphocytic leukemia (ALL), immune deficiency, or autoimmunity. Translocation of MLL1 (KMT2A) often results in a pro-B cell ALL, but little is known about its role in normal B cell differentiation. Using a Rag1-cre mouse knock-in to selectively delete Mll1 in developing lymphocytes, we show that B cell, but not T cell, homeostasis depends on MLL1...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29351983/partial-tandem-duplication-of-kmt2a-mll-may-predict-a-subset-of-myelodysplastic-syndrome-with-unique-characteristics-and-poor-outcome
#5
Sarah M Choi, Rajan Dewar, Patrick W Burke, Lina Shao
Partial tandem duplication (PTD) of the KMT2A (MLL) gene is a poor prognostic factor in acute myeloid leukemia, but its significance in the context of myelodysplastic syndrome (MDS) is unknown. Here, we used cytogenomic array to identify MLL-PTD in a group of MDS patients and compared their clinicopathologic characteristics with a cohort of high-risk MDS patients without MLL-PTD. We show that MLL-PTD defines a subset of MDS characterized by high blast count, normal karyotype, and extremely poor prognosis exceeding that of non-MLL-PTD high risk MDS, including those with complex karyotype...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351982/prevalence-and-characteristics-of-metabolic-syndrome-in-adults-from-the-french-childhood-leukemia-survivors-cohort-a-comparison-with-controls-from-the-french-population
#6
Claire Oudin, Julie Berbis, Yves Bertrand, Camille Vercasson, Frédérique Thomas, Pascal Chastagner, Stéphane Ducassou, Justyna Kanold, Marie-Dominique Tabone, Catherine Paillard, Marilyne Poirée, Dominique Plantaz, Jean-Hugues Dalle, Virginie Gandemer, Sandrine Thouvenin, Nicolas Sirvent, Paul Saultier, Sophie Béliard, Guy Leverger, André Baruchel, Pascal Auquier, Bruno Pannier, Gérard Michel
The prevalence of the metabolic syndrome among adults from the French childhood acute leukemia survivors' cohort was prospectively evaluated considering the type of anti-leukemic treatment received, and compared with that of controls. The metabolic profile of those patients was compared with that of controls. 3203 patients from a French volunteer cohort were age- and sex-matched 3:1 to 1025 leukemia survivors (in both cohorts, mean age: 24.4 years, female individuals: 51%). Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III criteria...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351753/mesenchymal-stem-cells-show-functional-defect-and-decreased-anti-cancer-effect-after-exposure-to-chemotherapeutic-drugs
#7
Chinnapaka Somaiah, Atul Kumar, Renu Sharma, Amit Sharma, Trishna Anand, Jina Bhattacharyya, Damodar Das, Sewali Deka Talukdar, Bithiah Grace Jaganathan
BACKGROUND: Mesenchymal stem cells (MSC) are used for several therapeutic applications to improve the functions of bone, cardiac, nervous tissue as well as to facilitate the repopulation of hematopoietic stem cells. MSC give rise to the non-hematopoietic stromal cells of the bone marrow and are important for the maintenance of normal hematopoiesis. Chemotherapeutic drugs used for treatment of leukemia extensively damage the stromal cells and alter their gene expression profiles. METHODS: We determined the changes in adipogenic, osteogenic differentiation, phenotypic and gene expression in MSC during treatment with chemotherapeutic drugs cytarabine, daunorubicin and vincristine...
January 19, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29351623/development-of-sugar-chain-binding-single-chain-variable-fragment-antibody-to-adult-t-cell-leukemia-cells-using-glyco-nanotechnology-and-phage-display-method
#8
Kaname Muchima, Taro Todaka, Hiroyuki Shinchi, Ayaka Sato, Arisa Tazoe, Rikiya Aramaki, Yuhei Kakitsubata, Risa Yokoyama, Naomichi Arima, Masanori Baba, Masahiro Wakao, Yuji Ito, Yasuo Suda
Adult T-cell leukemia (ATL) is an intractable blood cancer caused by the infection of human T-cell leukemia virus type-1, and effective medical treatment is required. It is known that the structure and expression levels of cell surface sugar chains vary depending on cell states such as inflammation and cancer. Thus, it is expected that the antibody specific for ATL cell surface sugar chain would be an effective diagnostic tool and a strong candidate for the development of an anti-ATL drug. Here, we developed a stable sugar chain binding single chain variable fragment antibody (scFv) that can bind to ATL cells using a fiber type Sugar Chip and phage display method...
January 17, 2018: Journal of Biochemistry
https://www.readbyqxmd.com/read/29351283/decreased-mir-17-in-glioma-cells-increased-cell-viability-and-migration-by-increasing-the-expression-of-cyclin-d1-p-akt-and-akt
#9
Guangwei Sun, Guozhong SiMa, Chunhui Wu, Yongzhong Fan, Yong Tan, Zhong Wang, Gang Cheng, Jie Li
BACKGROUND: The activating mutations of micro RNA (miR)-17 have been revealed in tumors such as human non-Hodgkin's lymphoma and T cell leukemia. However, it is unclear about the role of miR-17 in glioma cells. The current study aimed to investigate effects of miR-17 mimics or inhibitor on the viability and migration of rat glioma C6 cells, and explore possible mechanisms. METHODS: The expression of miR-17 in rat glioma C6 cells and normal brain tissue was detected by quantitative PCR...
2018: PloS One
https://www.readbyqxmd.com/read/29351208/preservation-method-and-phosphate-buffered-saline-washing-affect-the-acute-myeloid-leukemia-proteome
#10
Rebecca Wangen, Elise Aasebø, Andrea Trentani, Stein-Ove Døskeland, Øystein Bruserud, Frode Selheim, Maria Hernandez-Valladares
Acute myeloid leukemia (AML) primary cells can be isolated from peripheral blood, suspended with media containing bovine serum and cryoprotectant, and stored in liquid nitrogen before being processed for proteomic analysis by mass spectrometry (MS). The presence of bovine serum and human blood proteins in AML samples can hamper the identifications of proteins, and thereby reduce the proteome coverage of the study. Herein, we have established the effect of phosphate buffered saline (PBS) washing on AML patient samples stored in media...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29350920/crystal-structures-and-human-leukemia-cell-apoptosis-inducible-activities-of-parthenolide-analogues-isolated-from-piptocoma-rufescens
#11
Yulin Ren, Judith C Gallucci, Xinxin Li, Lichao Chen, Jianhua Yu, A Douglas Kinghorn
The molecular structures of three parthenolide analogues, (-)-goyazensolide (1), (-)-15-deoxygoyazensolide (2), and (-)-ereglomerulide (3), isolated from the leaves of Piptocoma rufescens in a previous study were determined by X-ray analysis, and the absolute configuration of (-)-goyazensolide (1) was confirmed crystallographically using Cu Kα radiation at low temperature. Compounds 1-3, (+)-rufesolide A (4), and commercial parthenolide were found to be growth inhibitory toward MOLM-13 and EOL-1 human acute myeloid leukemia cells using PKC412 (midostaurin) as the positive control, with 1-3 being more active than parthenolide...
January 19, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29350496/venoocclusive-disease-due-to-chemotherapy-for-pediatric-acute-lymphoblastic-leukemia-is-associated-with-increased-levels-of-plasminogen-activator-inhibitor-1
#12
Margherita Mauro, Graziella Saggiorato, Maria Teresa Sartori, Giuseppe Gallo, Massimiliano De Bortoli, Elisa Bonetti, Ada Zaccaron, Virginia Vitale, Rita Balter, Matteo Chinello, Simone Cesaro
We describe three cases of sinusoidal obstruction syndrome/venoocclusive disease (SOS) in pediatric patients with acute lymphoblastic leukemia (ALL). All three episodes occurred during or just after the induction or reinduction phase of treatment based on prednisone/dexamethasone, vincristine, daunorubicin, and pegylated-l-asparaginase. SOS episodes were categorized as mild/moderate and resolved in 7, 10, and 16 days using supportive measures or defibrotide therapy. In all three episodes, the clinical diagnosis of SOS was associated with a significant increase in plasminogen-activator inhibitor-1 (PAI-1) that reduced with patient clinical improvement...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29350461/is-testicular-irradiation-necessary-for-patients-with-acute-lymphoblastic-leukemia-and-testicular-relapse
#13
Ching-Hon Pui
No abstract text is available yet for this article.
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29349649/structure-activity-relationships-of-flavanones-flavanone-glycosides-and-flavones-in-anti-degranulation-activity-in-rat-basophilic-leukemia-rbl-2h3-cells
#14
Toshiro Noshita, Kaori Miura, Kaoru Ikeda, Hidekazu Ouchi, Takuya Matsumoto, Akihiro Tai
The incidence of type I allergies, which are associated with mast cell degranulation and local inflammation, is increasing, and new treatments are needed. To date, structure-activity relationships of flavonoids in their degranulation-inhibiting activity have not been systematically characterized. In the current study, the degranulation-inhibiting activity of a series of flavonoids was evaluated. The following three observations were made: (1) the activity disappears when a sugar moiety is introduced into the A ring of the flavanone; (2) the activity depends on the number of hydroxyl groups on the B ring; (3) the activity is markedly enhanced when a double bond is introduced into the C ring...
January 18, 2018: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29348881/allogeneic-stem-cell-transplantation-in-acute-lymphoblastic-leukemia-patients-older-than-60-years-a-survey-from-the-acute-leukemia-working-party-of-ebmt
#15
Gabrielle Roth-Guepin, Jonathan Canaani, Annalisa Ruggeri, Myriam Labopin, Juergen Finke, Jan J Cornelissen, Jeremy Delage, Gernot Stuhler, Monserrat Rovira, Mike Potter, Michael Stadler, Hendrik Veelken, Jean Yves Cahn, Matthew Collin, Yves Beguin, Sebastian Giebel, Arnon Nagler, Mohamad Mohty
Hematopoietic stem cell transplantation (HSCT) is being increasingly explored as a treatment modality for older patients with acute lymphoblastic leukemia (ALL). Yet, concerns regarding the long term outcome of transplantation in older patients limit the wide spread applicability of this approach. In this analysis we set out to determine the outcome of ALL patients over the age of 60 who underwent reduced intensity HSCT. Herein, we present the experience of the acute leukemia working party (ALWP) of the EBMT in this age group...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348865/targeting-t-cell-malignancies-using-anti-cd4-car-nk-92-cells
#16
Kevin G Pinz, Elizabeth Yakaboski, Alexander Jares, Hua Liu, Amelia E Firor, Kevin H Chen, Masayuki Wada, Huda Salman, William Tse, Nabil Hagag, Fengshuo Lan, Elaine Lai-Han Leung, Xun Jiang, Yupo Ma
Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non-Hodgkin's lymphomas (NHLs) with poor prognoses and account for a majority of T-cell malignancies. Overall, the standard of care for patients with T-cell malignancies is poorly established, and there is an urgent clinical need for a new approach. As demonstrated in B-cell malignancies, chimeric antigen receptor (CAR) immunotherapy provides great hope as a curative treatment regimen. Because PTCLs develop from mature T-cells, these NHLs are commonly CD4+, and CD4 is highly and uniformly expressed...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348817/a-mitochondrial-targeted-purine-based-hsp90-antagonist-for-leukemia-therapy
#17
Kelly G Bryant, Young Chan Chae, Rogelio L Martinez, John C Gordon, Khaled M Elokely, Andrew V Kossenkov, Steven Grant, Wayne E Childers, Magid Abou-Gharbia, Dario C Altieri
Reprogramming of mitochondrial functions sustains tumor growth and may provide therapeutic opportunities. Here, we targeted the protein folding environment in mitochondria by coupling a purine-based inhibitor of the molecular chaperone Heat Shock Protein-90 (Hsp90), PU-H71 to the mitochondrial-targeting moiety, triphenylphosphonium (TPP). Binding of PU-H71-TPP to ADP-Hsp90, Hsp90 co-chaperone complex or mitochondrial Hsp90 homolog, TRAP1 involved hydrogen bonds, π-π stacking, cation-π contacts and hydrophobic interactions with the surrounding amino acids in the active site...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348731/problems-with-precaution-the-transfusion-medicine-experience
#18
Kumanan Wilson, Katherine M Atkinson, Dean A Fergusson, Adalsteinn Brown, Alan Forster, Malia S Q Murphy, Alan T Tinmouth, Jennifer Keelan
The precautionary principle is a dominant paradigm governing risk-based decision-making. Today, there are increasing pressures to re-examine aggressive precautionary approaches, and to assess how the principle should be applied in the modern system. In this paper, we examined three key applications of precautionary approaches in the field of transfusion medicine to provide insight into the risks and benefits of these approaches. The three case studies examined were the donor deferral policies to safeguard against transfusion transmission of human immunodeficiency virus, variant Creutzfeldt-Jacob disease, and, lastly, xenotropic murine leukemia virus-related virus...
2018: Journal of Risk Research
https://www.readbyqxmd.com/read/29348612/gwas-in-childhood-acute-lymphoblastic-leukemia-reveals-novel-genetic-associations-at-chromosomes-17q12-and-8q24-21
#19
Joseph L Wiemels, Kyle M Walsh, Adam J de Smith, Catherine Metayer, Semira Gonseth, Helen M Hansen, Stephen S Francis, Juhi Ojha, Ivan Smirnov, Lisa Barcellos, Xiaorong Xiao, Libby Morimoto, Roberta McKean-Cowdin, Rong Wang, Herbert Yu, Josephine Hoh, Andrew T DeWan, Xiaomei Ma
Childhood acute lymphoblastic leukemia (ALL) (age 0-14 years) is 20% more common in Latino Americans than non-Latino whites. We conduct a genome-wide association study in a large sample of 3263 Californian children with ALL (including 1949 of Latino heritage) and 3506 controls matched on month and year of birth, sex, and ethnicity, and an additional 12,471 controls from the Kaiser Resource for Genetic Epidemiology Research on Aging Cohort. Replication of the strongest genetic associations is performed in two independent datasets from the Children's Oncology Group and the California Childhood Leukemia Study...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29348495/preclinical-evaluation-of-antitumor-activity-of-the-proteasome-inhibitor-mln2238-ixazomib-in-hepatocellular-carcinoma-cells
#20
Giuseppa Augello, Martina Modica, Antonina Azzolina, Roberto Puleio, Giovanni Cassata, Maria Rita Emma, Caterina Di Sano, Antonella Cusimano, Giuseppe Montalto, Melchiorre Cervello
Hepatocellular carcinoma (HCC) is one of the common malignancies and is an increasingly important cause of cancer death worldwide. Surgery, chemotherapy, and radiation therapy extend the 5-year survival limit in HCC patients by only 6%. Therefore, there is a need to develop new therapeutic approaches for the treatment of this disease. The orally bioavailable proteasome inhibitor MLN2238 (ixazomib) has been demonstrated to have anticancer activity. In the present study, we investigated the preclinical therapeutic efficacy of MLN2238 in HCC cells through in vitro and in vivo models, and examined its molecular mechanisms of action...
January 18, 2018: Cell Death & Disease
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