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Jaroslaw Maciejewski

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https://www.readbyqxmd.com/read/27863435/myb-expression-is-critical-for-myeloid-leukemia-development-induced-by-setbp1-activation
#1
Nhu Nguyen, Bandana A Vishwakarma, Kevin Oakley, Yufen Han, Bartlomiej Przychodzen, Jaroslaw P Maciejewski, Yang Du
SETBP1 missense mutations have been frequently identified in multiple myeloid neoplasms; however, their oncogenic potential remains unclear. Here we show that expression of Setbp1 mutants carrying two such mutations in mouse bone marrow progenitors efficiently induced development of acute myeloid leukemias (AMLs) in irradiated recipient mice with significantly shorter latencies and greater penetrance than expression of wild-type Setbp1, suggesting that these mutations are highly oncogenic. The increased oncogenicity of Setbp1 missense mutants could be due in part to their capability to drive significantly higher target gene transcription...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27697773/high-incidence-of-activating-stat5b-mutations-in-cd4-positive-t-cell-large-granular-lymphocyte-leukemia
#2
Emma Andersson, Takahiro Tanahashi, Nodoka Sekiguchi, Vanessa Rebecca Gasparini, Sabrina Bortoluzzi, Toru Kawakami, Kazuyuki Matsuda, Takeki Mitsui, Samuli Eldfors, Stefania Bortoluzzi, Alessandro Coppe, Andrea Binatti, Sonja Lagström, Pekka Ellonen, Noriyasu Fukushima, Sayaka Nishina, Noriko Senoo, Hitoshi Sakai, Hideyuki Nakazawa, Yok-Lam Kwong, Thomas P Loughran, Jaroslaw P Maciejewski, Satu Mustjoki, Fumihiro Ishida
No abstract text is available yet for this article.
October 3, 2016: Blood
https://www.readbyqxmd.com/read/27538433/connect-mds-aml-design-of-the-myelodysplastic-syndromes-and-acute-myeloid-leukemia-disease-registry-a-prospective-observational-cohort-study
#3
David P Steensma, Medrdad Abedi, Rafael Bejar, Christopher R Cogle, Kathryn Foucar, Guillermo Garcia-Manero, Tracy I George, David Grinblatt, Rami Komrokji, Xiaomei Ma, Jaroslaw Maciejewski, Daniel A Pollyea, Michael R Savona, Bart Scott, Mikkael A Sekeres, Michael A Thompson, Arlene S Swern, Melissa Nifenecker, Mary M Sugrue, Harry Erba
BACKGROUND: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms in which outgrowth of neoplastic clones disrupts normal hematopoiesis. Some patients with unexplained persistent cytopenias may not meet minimal diagnostic criteria for MDS but an alternate diagnosis is not apparent; the term idiopathic cytopenia of undetermined significance (ICUS) has been used to describe this state. MDS and AML occur primarily in older patients who are often treated outside the clinical trial setting...
August 19, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27535995/cytopenia-levels-for-aiding-establishment-of-the-diagnosis-of-myelodysplastic-syndromes
#4
Peter L Greenberg, Heinz Tuechler, Julie Schanz, Guillermo Sanz, Guillermo Garcia-Manero, Francesc Solé, John M Bennett, David Bowen, Pierre Fenaux, Francois Dreyfus, Hagop Kantarjian, Andrea Kuendgen, Alessandro Levis, Luca Malcovati, Mario Cazzola, Jaroslav Cermak, Christa Fonatsch, Michelle M Le Beau, Marilyn L Slovak, Otto Krieger, Michael Luebbert, Jaroslaw Maciejewski, Silvia M M Magalhaes, Yasushi Miyazaki, Michael Pfeilstöcker, Mikkael Sekeres, Wolfgang R Sperr, Reinhard Stauder, Sudhir Tauro, Peter Valent, Teresa Vallespi, Arjan A van de Loosdrecht, Ulrich Germing, Detlef Haase
No abstract text is available yet for this article.
August 17, 2016: Blood
https://www.readbyqxmd.com/read/27335276/time-dependent-changes-in-mortality-and-transformation-risk-in-mds
#5
Michael Pfeilstöcker, 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, Alessandro Levis, Michael Luebbert, Jaroslaw Maciejewski, Sigrid Machherndl-Spandl, Silvia M M Magalhaes, Yasushi Miyazaki, 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
In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database...
August 18, 2016: Blood
https://www.readbyqxmd.com/read/27216773/epigenetic-therapy-as-a-novel-approach-for-gfi136n-associated-murine-human-aml
#6
Lacramioara Botezatu, Lars C Michel, Anne Helness, Charles Vadnais, Hideki Makishima, Judith M Hönes, François Robert, Lothar Vassen, Aniththa Thivakaran, Yahya Al-Matary, Robert F Lams, Judith Schütte, Bernd Giebel, André Görgens, Michael Heuser, Hind Medyouf, Jaroslaw Maciejewski, Ulrich Dührsen, Tarik Möröy, Cyrus Khandanpour
Epigenetic changes can contribute to development of acute myeloid leukemia (AML), a malignant disease of the bone marrow. A single-nucleotide polymorphism of transcription factor growth factor independence 1 (GFI1) generates a protein with an asparagine at position 36 (GFI1(36N)) instead of a serine at position 36 (GFI1(36S)), which is associated with de novo AML in humans. However, how GFI1(36N) predisposes to AML is poorly understood. To explore the mechanism, we used knock-in mouse strains expressing GFI1(36N) or GFI1(36S)...
August 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27080012/gfi1-36n-as-a-therapeutic-and-prognostic-marker-for-myelodysplastic-syndrome
#7
Lacramioara Botezatu, Lars C Michel, Hideki Makishima, Thomas Schroeder, Ulrich Germing, Rainer Haas, Bert van der Reijden, Anne E Marneth, Saskia M Bergevoet, Joop H Jansen, Bartlomiej Przychodzen, Marcin Wlodarski, Charlotte Niemeyer, Uwe Platzbecker, Gerhard Ehninger, Ashwin Unnikrishnan, Dominik Beck, John Pimanda, Eva Hellström-Lindberg, Luca Malcovati, Jacqueline Boultwood, Andrea Pellagatti, Elli Papaemmanuil, Philipp Le Coutre, Jaspal Kaeda, Bertram Opalka, Tarik Möröy, Ulrich Dührsen, Jaroslaw Maciejewski, Cyrus Khandanpour
Inherited gene variants play an important role in malignant diseases. The transcriptional repressor growth factor independence 1 (GFI1) regulates hematopoietic stem cell (HSC) self-renewal and differentiation. A single-nucleotide polymorphism of GFI1 (rs34631763) generates a protein with an asparagine (N) instead of a serine (S) at position 36 (GFI1(36N)) and has a prevalence of 3%-5% among Caucasians. Because GFI1 regulates myeloid development, we examined the role of GFI1(36N) on the course of MDS disease...
July 2016: Experimental Hematology
https://www.readbyqxmd.com/read/26992944/the-efficacy-of-current-prognostic-models-in-predicting-outcome-of-patients-with-myelodysplastic-syndromes-at-the-time-of-hypomethylating-agent-failure
#8
LETTER
Aziz Nazha, Rami S Komrokji, Guillermo Garcia-Manero, John Barnard, Gail J Roboz, David P Steensma, Amy E DeZern, Katrina Zell, Cassie Zimmerman, Najla Al Ali, Elias Jabbour, Molly D Greenberg, Hagop M Kantarjian, Jaroslaw P Maciejewski, Alan F List, Mikkael A Sekeres
No abstract text is available yet for this article.
June 2016: Haematologica
https://www.readbyqxmd.com/read/26799334/impact-of-allogeneic-hematopoietic-cell-transplant-in-patients-with-myeloid-neoplasms-carrying-spliceosomal-mutations
#9
Betty Ky Hamilton, Valeria Visconte, Xuefei Jia, Ali Tabarroki, Hideki Makishima, Edy Hasrouni, Donna Abounader, Matt Kalaycio, Mikkael A Sekeres, Ronald Sobecks, Hien Duong Liu, Brian Bolwell, Jaroslaw P Maciejewski, Edward Copelan, Ramon V Tiu
Molecular predictors of outcome are increasingly important in determining optimal therapy for myeloid neoplasms. Mutations in the spliceosomal genes (U2AF1 and SRSF2) predict for poor outcomes in myelodysplastic syndromes (MDS) and related diseases. We investigated the effect of hematopoietic cell transplant (HCT) on the negative prognostic impact of U2AF1 and SRSF2 mutations. In total, 122 patients with MDS (30%), acute myeloid leukemia (51%), myeloproliferative neoplasms (MPN) (11%), and MDS/MPN (8%) receiving a HCT from 2003 to 2012 were evaluated for mutations in U2AF1 and SRSF2 by direct sequencing...
June 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/26777537/outcomes-of-patients-with-myelodysplastic-syndromes-who-achieve-stable-disease-after-treatment-with-hypomethylating-agents
#10
Aziz Nazha, Mikkael A Sekeres, Guillermo Garcia-Manero, John Barnard, Najla H Al Ali, Gail J Roboz, David P Steensma, Amy E DeZern, Cassie Zimmerman, Elias J Jabbour, Katrina Zell, Alan F List, Hagop M Kantarjian, Jaroslaw P Maciejewski, Rami S Komrokji
Treatment with hypomethylating agents (HMAs) improves overall survival (OS) in patients who achieve a response of stable disease (SD) or better (complete remission [CR], partial remission [PR], or hematologic improvement [HI]). It is not well established if patients who achieve SD at 4-6 months of therapy should be offered different therapies to optimize their response or continue with the same regimen. Clinical data were obtained from the MDS Clinical Research Consortium database. SD was defined as no evidence of progression and without achievement of any other responses...
February 2016: Leukemia Research
https://www.readbyqxmd.com/read/26720758/aberrant-dna-methylation-is-associated-with-a-poor-outcome-in-juvenile-myelomonocytic-leukemia
#11
Hirotoshi Sakaguchi, Hideki Muramatsu, Yusuke Okuno, Hideki Makishima, Yinyan Xu, Yoko Furukawa-Hibi, Xinan Wang, Atsushi Narita, Kenichi Yoshida, Yuichi Shiraishi, Sayoko Doisaki, Nao Yoshida, Asahito Hama, Yoshiyuki Takahashi, Kiyofumi Yamada, Satoru Miyano, Seishi Ogawa, Jaroslaw P Maciejewski, Seiji Kojima
Juvenile myelomonocytic leukemia (JMML), an overlap of myelodysplastic / myeloproliferative neoplasm, is an intractable pediatric myeloid neoplasm. Epigenetic regulation of transcription, particularly by CpG methylation, plays an important role in tumor progression, mainly by repressing tumor-suppressor genes. To clarify the clinical importance of aberrant DNA methylation, we studied the hypermethylation status of 16 target genes in the genomes of 92 patients with JMML by bisulfite conversion and the pryosequencing technique...
2015: PloS One
https://www.readbyqxmd.com/read/26702063/prevalence-clinical-characteristics-and-prognosis-of-gata2-related-myelodysplastic-syndromes-in-children-and-adolescents
#12
Marcin W Wlodarski, Shinsuke Hirabayashi, Victor Pastor, Jan Starý, Henrik Hasle, Riccardo Masetti, Michael Dworzak, Markus Schmugge, Marry van den Heuvel-Eibrink, Marek Ussowicz, Barbara De Moerloose, Albert Catala, Owen P Smith, Petr Sedlacek, Arjan C Lankester, Marco Zecca, Victoria Bordon, Susanne Matthes-Martin, Jonas Abrahamsson, Jörn Sven Kühl, Karl-Walter Sykora, Michael H Albert, Bartlomiej Przychodzien, Jaroslaw P Maciejewski, Stephan Schwarz, Gudrun Göhring, Brigitte Schlegelberger, Annámaria Cseh, Peter Noellke, Ayami Yoshimi, Franco Locatelli, Irith Baumann, Brigitte Strahm, Charlotte M Niemeyer
Germline GATA2 mutations cause cellular deficiencies with high propensity for myeloid disease. We investigated 426 children and adolescents with primary myelodysplastic syndrome (MDS) and 82 cases with secondary MDS enrolled in 2 consecutive prospective studies of the European Working Group of MDS in Childhood (EWOG-MDS) conducted in Germany over a period of 15 years. Germline GATA2 mutations accounted for 15% of advanced and 7% of all primary MDS cases, but were absent in children with MDS secondary to therapy or acquired aplastic anemia...
March 17, 2016: Blood
https://www.readbyqxmd.com/read/26574844/angioimmunoblastic-t-cell-lymphomas-with-the-rhoa-p-gly17val-mutation-have-classic-clinical-and-pathologic-features
#13
Sarah L Ondrejka, Bartosz Grzywacz, Juraj Bodo, Hideki Makishima, Chantana Polprasert, Jonathan W Said, Bartlomiej Przychodzen, Jaroslaw P Maciejewski, Eric D Hsi
Angioimmunoblastic T-cell lymphoma (AITL) is a nodal-based mature T-cell lymphoma with distinctive clinical symptomatology and histology. Research into its pathogenesis supports a cellular derivation from follicular helper T cells and overexpression of genes related to B cells, follicular dendritic cells, and vascular growth. Recently, a novel recurring somatic mutation in RHOA, encoding p.Gly17Val, was discovered in nearly 70% of AITLs and in a smaller proportion of peripheral T-cell lymphomas, not otherwise specified (PTCL-NOS)...
March 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/26509444/impact-of-snp-array-karyotyping-on-the-diagnosis-and-the-outcome-of-chronic-myelomonocytic-leukemia-with-low-risk-cytogenetic-features-or-no-metaphases
#14
Laura Palomo, Blanca Xicoy, Olga Garcia, Mar Mallo, Vera Ademà, Marta Cabezón, Montse Arnan, Helena Pomares, María José Larrayoz, María José Calasanz, Jaroslaw P Maciejewski, Dayong Huang, Lee-Yung Shih, Seishi Ogawa, Jose Cervera, Esperanza Such, Rosa Coll, Javier Grau, Francesc Solé, Lurdes Zamora
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder with heterogeneous clinical, morphological and genetic characteristics. Clonal cytogenetic abnormalities are found in 20-30% of patients with CMML. Patients with low risk cytogenetic features (normal karyotype and isolated loss of Y chromosome) account for ∼80% of CMML patients and often fall into the low risk categories of CMML prognostic scores. We hypothesized that single nucleotide polymorphism arrays (SNP-A) karyotyping could detect cryptic chromosomal alterations with prognostic impact in these subgroup of patients...
February 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/26458771/loss-of-tifab-a-del-5q-mds-gene-alters-hematopoiesis-through-derepression-of-toll-like-receptor-traf6-signaling
#15
Melinda E Varney, Madeline Niederkorn, Hiroyasu Konno, Takayuki Matsumura, Jin Gohda, Nobuaki Yoshida, Taishin Akiyama, Susanne Christie, Jing Fang, David Miller, Andres Jerez, Aly Karsan, Jaroslaw P Maciejewski, Ruhikanta A Meetei, Jun-ichiro Inoue, Daniel T Starczynowski
TRAF-interacting protein with forkhead-associated domain B (TIFAB) is a haploinsufficient gene in del(5q) myelodysplastic syndrome (MDS). Deletion of Tifab results in progressive bone marrow (BM) and blood defects, including skewed hematopoietic stem/progenitor cell (HSPC) proportions and altered myeloid differentiation. A subset of mice transplanted with Tifab knockout (KO) HSPCs develop a BM failure with neutrophil dysplasia and cytopenia. In competitive transplants, Tifab KO HSPCs are out-competed by wild-type (WT) cells, suggesting a cell-intrinsic defect...
October 19, 2015: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/26453823/whole-exome-sequencing-enhances-prognostic-classification-of-myeloid-malignancies
#16
Matthew Ruffalo, Holleh Husseinzadeh, Hideki Makishima, Bartlomiej Przychodzen, Mohamed Ashkar, Mehmet Koyutürk, Jaroslaw P Maciejewski, Thomas LaFramboise
PURPOSE: To date the standard nosology and prognostic schemes for myeloid neoplasms have been based on morphologic and cytogenetic criteria. We sought to test the hypothesis that a comprehensive, unbiased analysis of somatic mutations may allow for an improved classification of these diseases to predict outcome (overall survival). EXPERIMENTAL DESIGN: We performed whole-exome sequencing (WES) of 274 myeloid neoplasms, including myelodysplastic syndrome (MDS, N=75), myelodysplastic/myeloproliferative neoplasia (MDS/MPN, N=33), and acute myeloid leukemia (AML, N=22), augmenting the resulting mutational data with public WES results from AML (N=144)...
December 2015: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/26438361/dose-dependent-role-of-the-cohesin-complex-in-normal-and-malignant-hematopoiesis
#17
Aaron D Viny, Christopher J Ott, Barbara Spitzer, Martin Rivas, Cem Meydan, Efthymia Papalexi, Dana Yelin, Kaitlyn Shank, Jaime Reyes, April Chiu, Yevgeniy Romin, Vitaly Boyko, Swapna Thota, Jaroslaw P Maciejewski, Ari Melnick, James E Bradner, Ross L Levine
Cohesin complex members have recently been identified as putative tumor suppressors in hematologic and epithelial malignancies. The cohesin complex guides chromosome segregation; however, cohesin mutant leukemias do not show genomic instability. We hypothesized that reduced cohesin function alters chromatin structure and disrupts cis-regulatory architecture of hematopoietic progenitors. We investigated the consequences of Smc3 deletion in normal and malignant hematopoiesis. Biallelic Smc3 loss induced bone marrow aplasia with premature sister chromatid separation and revealed an absolute requirement for cohesin in hematopoietic stem cell (HSC) function...
October 19, 2015: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/26416416/tp53-and-mdm2-single-nucleotide-polymorphisms-influence-survival-in-non-del-5q-myelodysplastic-syndromes
#18
Kathy L McGraw, Thomas Cluzeau, David A Sallman, Ashley A Basiorka, Brittany A Irvine, Ling Zhang, P K Epling-Burnette, Dana E Rollison, Mar Mallo, Lubomir Sokol, Francesc Solé, Jaroslaw Maciejewski, Alan F List
P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases...
October 27, 2015: Oncotarget
https://www.readbyqxmd.com/read/26375552/cx25-contributes-to-leukemia-cell-communication-and-chemosensitivity
#19
Maksim Sinyuk, Alvaro G Alvarado, Pavel Nesmiyanov, Jeremy Shaw, Erin E Mulkearns-Hubert, Jennifer T Eurich, James S Hale, Anna Bogdanova, Masahiro Hitomi, Jaroslaw Maciejewski, Alex Y Huang, Yogen Saunthararajah, Justin D Lathia
Leukemia encompasses several hematological malignancies with shared phenotypes that include rapid proliferation, abnormal leukocyte self-renewal, and subsequent disruption of normal hematopoiesis. While communication between leukemia cells and the surrounding stroma supports tumor survival and expansion, the mechanisms underlying direct leukemia cell-cell communication and its contribution to tumor growth are undefined. Gap junctions are specialized intercellular connections composed of connexin proteins that allow free diffusion of small molecules and ions directly between the cytoplasm of adjacent cells...
October 13, 2015: Oncotarget
https://www.readbyqxmd.com/read/26363012/radioprotection-of-idh1-mutated-cancer-cells-by-the-idh1-mutant-inhibitor-agi-5198
#20
Remco J Molenaar, Dennis Botman, Myrthe A Smits, Vashendriya V Hira, Sanne A van Lith, Jan Stap, Peter Henneman, Mohammed Khurshed, Krissie Lenting, Adri N Mul, Dionysia Dimitrakopoulou, Cornelis M van Drunen, Ron A Hoebe, Tomas Radivoyevitch, Johanna W Wilmink, Jaroslaw P Maciejewski, W Peter Vandertop, William P Leenders, Fonnet E Bleeker, Cornelis J van Noorden
Isocitrate dehydrogenase 1 (IDH1) is mutated in various types of human cancer to IDH1(R132H), a structural alteration that leads to catalysis of α-ketoglutarate to the oncometabolite D-2-hydroxyglutarate. In this study, we present evidence that small-molecule inhibitors of IDH1(R132H) that are being developed for cancer therapy may pose risks with coadministration of radiotherapy. Cancer cells heterozygous for the IDH1(R132H) mutation exhibited less IDH-mediated production of NADPH, such that after exposure to ionizing radiation (IR), there were higher levels of reactive oxygen species, DNA double-strand breaks, and cell death compared with IDH1 wild-type cells...
November 15, 2015: Cancer Research
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