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Jaroslaw Maciejewski

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https://www.readbyqxmd.com/read/28983059/pro-inflammatory-proteins-s100a9-and-tnf%C3%AE-suppress-erythropoietin-elaboration-in-myelodysplastic-syndromes
#1
Thomas Cluzeau, Kathy L McGraw, Brittany Irvine, Erico Masala, Lionel Ades, Ashley A Basiorka, Jaroslaw P Maciejewski, Patrick Auberger, Sheng Wei, Pierre Fenaux, Valeria Santini, Alan List
Accumulating evidence implicates innate immune activation in the pathobiology of myelodysplastic syndromes. A key myeloid related inflammatory protein, S100A9, serves as a Toll-like receptor ligand regulating TNFα and IL-1β production. The role of MDS-related inflammatory proteins in endogenous Epo regulation and response to erythroid stimulating agents or lenalidomide has not been investigated. The HepG2 hepatoma cell line was used to investigate in vitro Epo elaboration. Serum collected from 311 MDS patients were investigated (125 prior to erythroid stimulating agents and 186 prior to lenalidomide)...
October 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28893734/origins-of-myelodysplastic-syndromes-after-aplastic-anemia
#2
LETTER
Eiju Negoro, Yasunobu Nagata, Michael J Clemente, Naoko Hosono, Wenyi Shen, Aziz Nazha, Tetsuichi Yoshizato, Cassandra Hirsch, Bartlomiej Przychodzen, Reda Z Mahfouz, Teodora Kuzmanovic, Mikkael A Sekeres, Hideki Makishima, Seishi Ogawa, Jaroslaw P Maciejewski
No abstract text is available yet for this article.
October 26, 2017: Blood
https://www.readbyqxmd.com/read/28758902/gata4-loss-of-function-in-liver-cancer-impedes-precursor-to-hepatocyte-transition
#3
Francis O Enane, Wai Ho Shuen, Xiaorong Gu, Ebrahem Quteba, Bartlomiej Przychodzen, Hideki Makishima, Juraj Bodo, Joanna Ng, Chit Lai Chee, Rebecca Ba, Lip Seng Koh, Janice Lim, Rachael Cheong, Marissa Teo, Zhenbo Hu, Kwok Peng Ng, Jaroslaw Maciejewski, Tomas Radivoyevitch, Alexander Chung, London Lucien Ooi, Yu Meng Tan, Peng-Chung Cheow, Pierce Chow, Chung Yip Chan, Kiat Hon Lim, Lisa Yerian, Eric Hsi, Han Chong Toh, Yogen Saunthararajah
The most frequent chromosomal structural loss in hepatocellular carcinoma (HCC) is of the short arm of chromosome 8 (8p). Genes on the remaining homologous chromosome, however, are not recurrently mutated, and the identity of key 8p tumor-suppressor genes (TSG) is unknown. In this work, analysis of minimal commonly deleted 8p segments to identify candidate TSG implicated GATA4, a master transcription factor driver of hepatocyte epithelial lineage fate. In a murine model, liver-conditional deletion of 1 Gata4 allele to model the haploinsufficiency seen in HCC produced enlarged livers with a gene expression profile of persistent precursor proliferation and failed hepatocyte epithelial differentiation...
September 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28650479/aml1-eto-requires-enhanced-c-d-box-snorna-rnp-formation-to-induce-self-renewal-and-leukaemia
#4
Fengbiao Zhou, Yi Liu, Christian Rohde, Cornelius Pauli, Dennis Gerloff, Marcel Köhn, Danny Misiak, Nicole Bäumer, Chunhong Cui, Stefanie Göllner, Thomas Oellerich, Hubert Serve, Maria-Paz Garcia-Cuellar, Robert Slany, Jaroslaw P Maciejewski, Bartlomiej Przychodzen, Barbara Seliger, Hans-Ulrich Klein, Christoph Bartenhagen, Wolfgang E Berdel, Martin Dugas, Makoto Mark Taketo, Daneyal Farouq, Schraga Schwartz, Aviv Regev, Josée Hébert, Guy Sauvageau, Caroline Pabst, Stefan Hüttelmaier, Carsten Müller-Tidow
Leukaemogenesis requires enhanced self-renewal, which is induced by oncogenes. The underlying molecular mechanisms remain incompletely understood. Here, we identified C/D box snoRNAs and rRNA 2'-O-methylation as critical determinants of leukaemic stem cell activity. Leukaemogenesis by AML1-ETO required expression of the groucho-related amino-terminal enhancer of split (AES). AES functioned by inducing snoRNA/RNP formation via interaction with the RNA helicase DDX21. Similarly, global loss of C/D box snoRNAs with concomitant loss of rRNA 2'-O-methylation resulted in decreased leukaemia self-renewal potential...
July 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28637623/ddx41-related-myeloid-neoplasia
#5
REVIEW
Jaroslaw P Maciejewski, Richard A Padgett, Anna L Brown, Carsten Müller-Tidow
While early presentation of familial leukemia syndromes is typical, long disease anticipation may mask cases of familial traits in seemingly spontaneous disease. Germline mutations in DDX41 gene have been discovered in several leukemia families, as well as in mostly adult patients with seemingly spontaneous disease but having strong family histories of myeloid neoplasia. As with other familial genes, DDX41 mutation carriers can develop neoplasia through acquisition of another somatic mutation, thereby affecting both DDX41 alleles...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28633612/clinical-features-and-treatment-outcomes-in-large-granular-lymphocytic-leukemia-lgll
#6
Srinivasa R Sanikommu, Michael J Clemente, Peter Chomczynski, Manuel G Afable, Andres Jerez, Swapna Thota, Bhumika Patel, Cassandra Hirsch, Aziz Nazha, John Desamito, Alan Lichtin, Brad Pohlman, Mikkael A Sekeres, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Large granular lymphocytic leukemia (LGLL) represents a clonal/oligoclonal lymphoproliferation of cytotoxic T and natural killer cells often associated with STAT3 mutations. When symptomatic, due to mostly anemia and neutropenia, therapy choices are often empirically-based, because only few clinical trials and systematic studies have been performed. Incorporating new molecular and flow cytometry parameters, we identified 204 patients fulfilling uniform criteria for LGLL diagnoses and analyzed clinical course with median follow-up of 36 months, including responses to treatments...
February 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28440315/tet2-loss-leads-to-hypermutagenicity-in-haematopoietic-stem-progenitor-cells
#7
Feng Pan, Thomas S Wingo, Zhigang Zhao, Rui Gao, Hideki Makishima, Guangbo Qu, Li Lin, Miao Yu, Janice R Ortega, Jiapeng Wang, Aziz Nazha, Li Chen, Bing Yao, Can Liu, Shi Chen, Ophelia Weeks, Hongyu Ni, Brittany Lynn Phillips, Suming Huang, Jianlong Wang, Chuan He, Guo-Min Li, Tomas Radivoyevitch, Iannis Aifantis, Jaroslaw P Maciejewski, Feng-Chun Yang, Peng Jin, Mingjiang Xu
TET2 is a dioxygenase that catalyses multiple steps of 5-methylcytosine oxidation. Although TET2 mutations frequently occur in various types of haematological malignancies, the mechanism by which they increase risk for these cancers remains poorly understood. Here we show that Tet2(-/-) mice develop spontaneous myeloid, T- and B-cell malignancies after long latencies. Exome sequencing of Tet2(-/-) tumours reveals accumulation of numerous mutations, including Apc, Nf1, Flt3, Cbl, Notch1 and Mll2, which are recurrently deleted/mutated in human haematological malignancies...
April 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28363872/novel-therapeutic-strategies-to-target-leukemic-cells-that-hijack-compartmentalized-continuous-hematopoietic-stem-cell-niches
#8
REVIEW
Vashendriya V V Hira, Cornelis J F Van Noorden, Hetty E Carraway, Jaroslaw P Maciejewski, Remco J Molenaar
Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are needed to generate blood cell precursors that are committed to unilineage differentiation and eventually production of mature blood cells, including red blood cells, megakaryocytes, myeloid cells and lymphocytes...
August 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28323261/corrigendum-ubiquitination-of-hnrnpa1-by-traf6-links-chronic-innate-immune-signaling-with-myelodysplasia
#9
Jing Fang, Lyndsey C Bolanos, Kwangmin Choi, Xiaona Liu, Susanne Christie, Shailaja Akunuru, Rupali Kumar, Dehua Wang, Xiaoting Chen, Kenneth D Greis, Peter Stoilov, Marie-Dominique Filippi, Jaroslaw P Maciejewski, Guillermo Garcia-Manero, Matthew T Weirauch, Nathan Salamonis, Hartmut Geiger, Yi Zheng, Daniel T Starczynowski
No abstract text is available yet for this article.
March 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28255022/molecular-features-of-early-onset-adult-myelodysplastic-syndrome
#10
Cassandra M Hirsch, Bartlomiej P Przychodzen, Tomas Radivoyevitch, Bhumika Patel, Swapna Thota, Michael J Clemente, Yasunobu Nagata, Thomas LaFramboise, Hetty E Carraway, Aziz Nazha, Mikkael A Sekeres, Hideki Makishima, Jaroslaw P Maciejewski
Myelodysplastic syndromes are typically diseases of older adults. Patients in whom the onset is early may have distinct molecular and clinical features or reflect a demographic continuum. The identification of differences between "early onset" patients and those diagnosed at a traditional age has the potential to advance understanding of the pathogenesis of myelodysplasia and may lead to formation of distinct morphological subcategories. We studied a cohort of 634 patients with various subcategories of myelodysplastic syndrome and secondary acute myeloid leukemia, stratifying them based on age at presentation and clinical parameters...
June 2017: Haematologica
https://www.readbyqxmd.com/read/28223278/genetic-abnormalities-in-myelodysplasia-and-secondary-acute-myeloid-leukemia-impact-on-outcome-of-stem-cell-transplantation
#11
Tetsuichi Yoshizato, Yasuhito Nannya, Yoshiko Atsuta, Yusuke Shiozawa, Yuka Iijima-Yamashita, Kenichi Yoshida, Yuichi Shiraishi, Hiromichi Suzuki, Yasunobu Nagata, Yusuke Sato, Nobuyuki Kakiuchi, Keitaro Matsuo, Makoto Onizuka, Keisuke Kataoka, Kenichi Chiba, Hiroko Tanaka, Hiroo Ueno, Masahiro M Nakagawa, Bartlomiej Przychodzen, Claudia Haferlach, Wolfgang Kern, Kosuke Aoki, Hidehiro Itonaga, Yoshinobu Kanda, Mikkael A Sekeres, Jaroslaw P Maciejewski, Torsten Haferlach, Yasushi Miyazaki, Keizo Horibe, Masashi Sanada, Satoru Miyano, Hideki Makishima, Seishi Ogawa
Genetic alterations, including mutations and copy-number alterations, are central to the pathogenesis of myelodysplastic syndromes and related diseases (myelodysplasia), but their roles in allogeneic stem cell transplantation have not fully been studied in a large cohort of patients. We enrolled 797 patients who had been diagnosed with myelodysplasia at initial presentation and received transplantation via the Japan Marrow Donor Program. Targeted-capture sequencing was performed to identify mutations in 69 genes, together with copy-number alterations, whose effects on transplantation outcomes were investigated...
April 27, 2017: Blood
https://www.readbyqxmd.com/read/28031539/recurrent-genetic-defects-on-chromosome-5q-in-myeloid-neoplasms
#12
Naoko Hosono, Hideki Makishima, Reda Mahfouz, Bartlomiej Przychodzen, Kenichi Yoshida, Andres Jerez, Thomas LaFramboise, Chantana Polprasert, Michael J Clemente, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Masashi Sanada, Edward Cui, Amit K Verma, Michael A McDevitt, Alan F List, Yogen Saunthararajah, Mikkael A Sekeres, Jacqueline Boultwood, Seishi Ogawa, Jaroslaw P Maciejewski
BACKGROUND: Deletion of chromosome 5q (del(5q)) is the most common karyotypic abnormality in myeloid neoplasms. MATERIALS AND METHODS: To define the pathogenic molecular features associated with del(5q), next-generation sequencing was applied to 133 patients with myeloid neoplasms (MDS; N = 69, MDS/MPN; N = 5, sAML; N = 29, pAML; N = 30) with del(5q) as a sole abnormally or a part of complex karyotype and results were compared to molecular features of patients diploid for chr5...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28024152/ubiquitination-of-hnrnpa1-by-traf6-links-chronic-innate-immune-signaling-with-myelodysplasia
#13
Jing Fang, Lyndsey C Bolanos, Kwangmin Choi, Xiaona Liu, Susanne Christie, Shailaja Akunuru, Rupali Kumar, Dehua Wang, Xiaoting Chen, Kenneth D Greis, Peter Stoilov, Marie-Dominique Filippi, Jaroslaw P Maciejewski, Guillermo Garcia-Manero, Matthew T Weirauch, Nathan Salomonis, Hartmut Geiger, Yi Zheng, Daniel T Starczynowski
Toll-like receptor (TLR) activation contributes to premalignant hematologic conditions, such as myelodysplastic syndromes (MDS). TRAF6, a TLR effector with ubiquitin (Ub) ligase activity, is overexpressed in MDS hematopoietic stem/progenitor cells (HSPCs). We found that TRAF6 overexpression in mouse HSPC results in impaired hematopoiesis and bone marrow failure. Using a global Ub screen, we identified hnRNPA1, an RNA-binding protein and auxiliary splicing factor, as a substrate of TRAF6. TRAF6 ubiquitination of hnRNPA1 regulated alternative splicing of Arhgap1, which resulted in activation of the GTP-binding Rho family protein Cdc42 and accounted for hematopoietic defects in TRAF6-expressing HSPCs...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27992414/dynamics-of-clonal-evolution-in-myelodysplastic-syndromes
#14
Hideki Makishima, Tetsuichi Yoshizato, Kenichi Yoshida, Mikkael A Sekeres, Tomas Radivoyevitch, Hiromichi Suzuki, Bartlomiej Przychodzen, Yasunobu Nagata, Manja Meggendorfer, Masashi Sanada, Yusuke Okuno, Cassandra Hirsch, Teodora Kuzmanovic, Yusuke Sato, Aiko Sato-Otsubo, Thomas LaFramboise, Naoko Hosono, Yuichi Shiraishi, Kenichi Chiba, Claudia Haferlach, Wolfgang Kern, Hiroko Tanaka, Yusuke Shiozawa, Inés Gómez-Seguí, Holleh D Husseinzadeh, Swapna Thota, Kathryn M Guinta, Brittney Dienes, Tsuyoshi Nakamaki, Shuichi Miyawaki, Yogen Saunthararajah, Shigeru Chiba, Satoru Miyano, Lee-Yung Shih, Torsten Haferlach, Seishi Ogawa, Jaroslaw P Maciejewski
To elucidate differential roles of mutations in myelodysplastic syndromes (MDS), we investigated clonal dynamics using whole-exome and/or targeted sequencing of 699 patients, of whom 122 were analyzed longitudinally. Including the results from previous reports, we assessed a total of 2,250 patients for mutational enrichment patterns. During progression, the number of mutations, their diversity and clone sizes increased, with alterations frequently present in dominant clones with or without their sweeping previous clones...
February 2017: Nature Genetics
https://www.readbyqxmd.com/read/27863435/myb-expression-is-critical-for-myeloid-leukemia-development-induced-by-setbp1-activation
#15
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...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27697773/high-incidence-of-activating-stat5b-mutations-in-cd4-positive-t-cell-large-granular-lymphocyte-leukemia
#16
LETTER
Emma I 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.
November 17, 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
#17
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
#18
LETTER
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.
October 20, 2016: Blood
https://www.readbyqxmd.com/read/27335276/time-dependent-changes-in-mortality-and-transformation-risk-in-mds
#19
MULTICENTER STUDY
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
#20
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
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