Read by QxMD icon Read

Jaroslaw Maciejewski

Alexander Röth, Jaroslaw Maciejewski, Jun-Ichi Nishimura, Deepak Jain, Jeffrey I Weitz
OBJECTIVE: Paroxysmal nocturnal hemoglobinuria (PNH) is a severe, life-threatening disorder for which early diagnosis is essential. However, given the rarity of the disease and non-specificity of symptoms, correct diagnosis may be delayed or missed. While various hematologic guidelines note common signs and symptoms associated with PNH, international expert consensus based on real-world clinical experience and an actionable algorithm for non-specialists to facilitate screening and diagnosis are lacking...
March 12, 2018: European Journal of Haematology
Bartlomiej Przychodzen, Hideki Makishima, Mikkael A Sekeres, Suresh Kumar Balasubramanian, Swapna Thota, Bhumika J Patel, Michael Clemente, Cassandra Hirsch, Brittney Dienes, Jaroslaw P Maciejewski
Using next generation sequencing we have systematically analyzed a large cohort of 489 patients with bone marrow failure (BMF), including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), aplastic anemia (AA), and related conditions for the presence of germline (GL) alterations in Fanconi Anemia (FA) and telomerase genes. We have detected an increased frequency of heterozygous FA gene mutations in MDS and to lesser degree in AML suggesting that the presence of one normal allele may not be completely protective and indeed heterozygous FA lesions may have a long latency period before hematologic manifestation...
January 5, 2018: Oncotarget
Remco J Molenaar, Jaroslaw P Maciejewski, Johanna W Wilmink, Cornelis J F van Noorden
Isocitrate dehydrogenase 1 and 2 (IDH1/2) are key enzymes in cellular metabolism, epigenetic regulation, redox states, and DNA repair. IDH1/2 mutations are causal in the development and/or progression of various types of cancer due to supraphysiological production of D-2-hydroxyglutarate. In various tumor types, IDH1/2-mutated cancers predict for improved responses to treatment with irradiation or chemotherapy. The present review discusses the molecular basis of the sensitivity of IDH1/2-mutated cancers with respect to the function of mutated IDH1/2 in cellular processes and their interactions with novel IDH1/2-mutant inhibitors...
January 25, 2018: Oncogene
Remco J Molenaar, Tomas Radivoyevitch, Yasunobu Nagata, Mohammed Khurshed, Bartlomiej Przychodzen, Hideki Makishima, Mingjiang Xu, Fonnet E Bleeker, Johanna W Wilmink, Hetty Carraway, Sudipto Mukherjee, Mikkael A Sekeres, Cornelis J F Van Noorden, Jaroslaw P Maciejewski
PURPOSE: Somatic mutations in IDH1/2 occur in ~20% of patients with myeloid neoplasms, including acute myeloid leukemia (AML). IDH1/2MUT enzymes produce D-2-hydroxyglutarate (D2HG), which associates with increases in DNA damage and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor cells. Whether this also holds true for IDH1/2MUT AML is not known. EXPERIMENTAL DESIGN: Well-characterized primary IDH1MUT, IDH2MUT and IDH1/2WT AML cells were analyzed for DNA damage and responses to daunorubicin, ionizing radiation and PARP inhibitors...
January 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Caner Saygin, Cassandra Hirsch, Bartlomiej Przychodzen, Mikkael A Sekeres, Betty K Hamilton, Matt Kalaycio, Hetty E Carraway, Aaron T Gerds, Sudipto Mukherjee, Aziz Nazha, Ronald Sobecks, Christopher Goebel, Donna Abounader, Jaroslaw P Maciejewski, Anjali S Advani
Intermediate-risk acute myeloid leukemia (IR-AML) is a clinically heterogeneous disease, for which optimal post-remission therapy is debated. The utility of next-generation sequencing information in decision making for IR-AML has yet to be elucidated. We retrospectively studied 100 IR-AML patients, defined by European Leukemia Net classification, who had mutational information at diagnosis, received intensive chemotherapy and achieved complete remission (CR) at Cleveland Clinic (CC). The Cancer Genome Atlas (TCGA) data were used for validation...
January 10, 2018: Blood Cancer Journal
Jaroslaw P Maciejewski, Suresh K Balasubramanian
Recent technological advances in genomics have led to the discovery of new somatic mutations and have brought deeper insights into clonal diversity. This discovery has changed not only the understanding of disease mechanisms but also the diagnostics and clinical management of bone marrow failure. The clinical applications of genomics include enhancement of current prognostic schemas, prediction of sensitivity or refractoriness to treatments, and conceptualization and selective application of targeted therapies...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
Suresh Kumar Balasubramanian, Meena Sadaps, Swapna Thota, Mai Aly, Bartlomiej P Przychodzen, Cassandra M Hirsch, Valeria Visconte, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Pure red cell aplasia is an orphan disease, and as such lacks rationally established standard therapies. Most cases are idiopathic; a subset is antibody-mediated. There is overlap between idiopathic cases and those with T-cell large granular lymphocytic leukemia, hypogammaglobulinemia, and low-grade lymphomas. In each of the aforementioned, the pathogenetic mechanisms may involve autoreactive cytotoxic responses. We selected 62 uniformly diagnosed pure red cell aplasia patients and analyzed their pathophysiologic features and responsiveness to rationally applied first-line and salvage therapies in order to propose diagnostic and therapeutic algorithms that may be helpful in guiding the management of prospective patients, 52% of whom were idiopathic, while the others involved large granular lymphocytic leukemia, thymoma, and B-cell dyscrasia...
February 2018: Haematologica
Thomas Cluzeau, Kathy L McGraw, Brittany Irvine, Erico Masala, Lionel Ades, Ashley A Basiorka, Jaroslaw 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 tumor necrosis factor-α and interleukin-1β production. The role of myelodysplastic syndrome-related inflammatory proteins in endogenous erythropoietin regulation and response to erythroid-stimulating agents or lenalidomide has not been investigated. The HepG2 hepatoma cell line was used to investigate in vitro erythropoietin elaboration...
December 2017: Haematologica
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
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
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
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
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
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
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
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
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
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
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
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
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"