keyword
MENU ▼
Read by QxMD icon Read
search

ulrich steidl

keyword
https://www.readbyqxmd.com/read/29773641/il1rap-potentiates-multiple-oncogenic-signaling-pathways-in-aml
#1
Kelly Mitchell, Laura Barreyro, Tihomira I Todorova, Samuel J Taylor, Iléana Antony-Debré, Swathi-Rao Narayanagari, Luis A Carvajal, Joana Leite, Zubair Piperdi, Gopichand Pendurti, Ioannis Mantzaris, Elisabeth Paietta, Amit Verma, Kira Gritsman, Ulrich Steidl
The surface molecule interleukin-1 receptor accessory protein (IL1RAP) is consistently overexpressed across multiple genetic subtypes of acute myeloid leukemia (AML) and other myeloid malignancies, including at the stem cell level, and is emerging as a novel therapeutic target. However, the cell-intrinsic functions of IL1RAP in AML cells are largely unknown. Here, we show that targeting of IL1RAP via RNA interference, genetic deletion, or antibodies inhibits AML pathogenesis in vitro and in vivo, without perturbing healthy hematopoietic function or viability...
May 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29710195/multiple-myeloma-and-its-precursor-disease-among-firefighters-exposed-to-the-world-trade-center-disaster
#2
Ola Landgren, Rachel Zeig-Owens, Orsolya Giricz, David Goldfarb, Kaznouri Murata, Katie Thoren, Lakshmi Ramanathan, Malin Hultcrantz, Ahmet Dogan, George Nwankwo, Ulrich Steidl, Kith Pradhan, Charles B Hall, Hillel W Cohen, Nadia Jaber, Theresa Schwartz, Laura Crowley, Michael Crane, Shani Irby, Mayris P Webber, Amit Verma, David J Prezant
Importance: The World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood. Objective: To characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS...
April 26, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29650728/metabolic-struggls-after-flt3-inhibition-in-aml
#3
Samuel J Taylor, Ulrich Steidl
No abstract text is available yet for this article.
April 12, 2018: Blood
https://www.readbyqxmd.com/read/29643228/dual-inhibition-of-mdmx-and-mdm2-as-a-therapeutic-strategy-in-leukemia
#4
Luis A Carvajal, Daniela Ben Neriah, Adrien Senecal, Lumie Benard, Victor Thiruthuvanathan, Tatyana Yatsenko, Swathi-Rao Narayanagari, Justin C Wheat, Tihomira I Todorova, Kelly Mitchell, Charles Kenworthy, Vincent Guerlavais, D Allen Annis, Boris Bartholdy, Britta Will, Jesus D Anampa, Ioannis Mantzaris, Manuel Aivado, Robert H Singer, Robert A Coleman, Amit Verma, Ulrich Steidl
The tumor suppressor p53 is often inactivated via its interaction with endogenous inhibitors mouse double minute 4 homolog (MDM4 or MDMX) or mouse double minute 2 homolog (MDM2), which are frequently overexpressed in patients with acute myeloid leukemia (AML) and other cancers. Pharmacological disruption of both of these interactions has long been sought after as an attractive strategy to fully restore p53-dependent tumor suppressor activity in cancers with wild-type p53. Selective targeting of this pathway has thus far been limited to MDM2-only small-molecule inhibitors, which lack affinity for MDMX...
April 11, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29499131/dynamic-regulation-of-long-chain-fatty-acid-oxidation-by-a-noncanonical-interaction-between-the-mcl-1-bh3-helix-and-vlcad
#5
Silvia Escudero, Elma Zaganjor, Susan Lee, Christopher P Mill, Ann M Morgan, Emily B Crawford, Jiahao Chen, Thomas E Wales, Rida Mourtada, James Luccarelli, Gregory H Bird, Ulrich Steidl, John R Engen, Marcia C Haigis, Joseph T Opferman, Loren D Walensky
MCL-1 is a BCL-2 family protein implicated in the development and chemoresistance of human cancer. Unlike its anti-apoptotic homologs, Mcl-1 deletion has profound physiologic consequences, indicative of a broader role in homeostasis. We report that the BCL-2 homology 3 (BH3) α helix of MCL-1 can directly engage very long-chain acyl-CoA dehydrogenase (VLCAD), a key enzyme of the mitochondrial fatty acid β-oxidation (FAO) pathway. Proteomic analysis confirmed that the mitochondrial matrix isoform of MCL-1 (MCL-1Matrix ) interacts with VLCAD...
March 1, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29453291/lsd1-inhibition-exerts-its-antileukemic-effect-by-recommissioning-pu-1-and-c-ebp%C3%AE-dependent-enhancers-in-aml
#6
Monica Cusan, Sheng F Cai, Helai P Mohammad, Andrei Krivtsov, Alan Chramiec, Evangelia Loizou, Matthew D Witkin, Kimberly N Smitheman, Daniel G Tenen, Min Ye, Britta Will, Ulrich Steidl, Ryan G Kruger, Ross L Levine, Hugh Y Rienhoff, Richard P Koche, Scott A Armstrong
Epigenetic regulators are recurrently mutated and aberrantly expressed in acute myeloid leukemia (AML). Targeted therapies designed to inhibit these chromatin-modifying enzymes, such as the histone demethylase lysine-specific demethylase 1 (LSD1) and the histone methyltransferase DOT1L, have been developed as novel treatment modalities for these often refractory diseases. A common feature of many of these targeted agents is their ability to induce myeloid differentiation, suggesting that multiple paths toward a myeloid gene expression program can be engaged to relieve the differentiation blockade that is uniformly seen in AML...
April 12, 2018: Blood
https://www.readbyqxmd.com/read/29296859/hispanic-ethnicity-is-associated-with-younger-age-at-presentation-but-worse-survival-in-acute-myeloid-leukemia
#7
Karine Darbinyan, Aditi Shastri, Anjali Budhathoki, Daniel Helbig, Rose Snyder, Kith Pradhan, Junaid Saleh-Esa, Noah S Kornblum, Adam F Binder, Swati Goel, Murali Janakiram, Olga Derman, Kira Gritsman, Ulrich Steidl, Ira Braunschweig, Amit Verma, Ioannis Mantzaris
SEER data and a Bronx validation cohort demonstrate that Hispanics present with AML at younger age but have shorter survival than whites.Increased frequency of high-risk mutations in Hispanics provides a potential biologic explanation for poorer outcomes in Hispanics.
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29191840/macrocytosis-and-dysplastic-anemia-is-associated-with-the-cyclin-dependent-kinase-4-6-inhibitor-palbociclib-in-metastatic-breast-cancer
#8
LETTER
Jesus Anampa, Tamanna Haque, Irina Murakhovskaya, Yanhua Wang, Kimo Bachiashvili, Cristian Papazoglu, Kith Pradhan, Ulrich G Steidl, Joseph A Sparano, Amit Verma
No abstract text is available yet for this article.
March 2018: Haematologica
https://www.readbyqxmd.com/read/29164994/stat3-inhibition-as-a-therapeutic-strategy-for-leukemia
#9
Rubashruti Kanna, Gaurav Choudhary, Nandini Ramachandra, Ulrich Steidl, Amit Verma, Aditi Shastri
Leukemia is characterized by selective overgrowth of malignant hematopoietic stem cells (HSC's) that interfere with HSC differentiation. Cytoreductive chemotherapy can kill rapidly dividing cancerous cells but cannot eradicate the malignant HSC pool leading to relapses. Leukemic stem cells have several dysregulated pathways and the Janus kinases (JAKs) and signal transducer and activator of transcription (STAT) pathway are prominent among them. STAT3 is an important transcription factor that regulates cell growth, proliferation, and inhibits apoptosis...
November 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29083320/pharmacological-inhibition-of-the-transcription-factor-pu-1-in-leukemia
#10
Iléana Antony-Debré, Ananya Paul, Joana Leite, Kelly Mitchell, Hye Mi Kim, Luis A Carvajal, Tihomira I Todorova, Kenneth Huang, Arvind Kumar, Abdelbasset A Farahat, Boris Bartholdy, Swathi-Rao Narayanagari, Jiahao Chen, Alberto Ambesi-Impiombato, Adolfo A Ferrando, Ioannis Mantzaris, Evripidis Gavathiotis, Amit Verma, Britta Will, David W Boykin, W David Wilson, Gregory Mk Poon, Ulrich Steidl
The transcription factor PU.1 is often impaired in patients with acute myeloid leukemia (AML). Here, we used AML cells that already had low PU.1 levels and further inhibited PU.1 using either RNA interference or, to our knowledge, first-in-class small-molecule inhibitors of PU.1 that we developed specifically to allosterically interfere with PU.1-chromatin binding through interaction with the DNA minor groove that flanks PU.1-binding motifs. These small molecules of the heterocyclic diamidine family disrupted the interaction of PU...
December 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29017059/direct-activation-of-bax-by-btsa1-overcomes-apoptosis-resistance-in-acute-myeloid-leukemia
#11
Denis E Reyna, Thomas P Garner, Andrea Lopez, Felix Kopp, Gaurav S Choudhary, Ashwin Sridharan, Swathi-Rao Narayanagari, Kelly Mitchell, Baoxia Dong, Boris A Bartholdy, Loren D Walensky, Amit Verma, Ulrich Steidl, Evripidis Gavathiotis
The BCL-2 family protein BAX is a central mediator of apoptosis. Overexpression of anti-apoptotic BCL-2 proteins contributes to tumor development and resistance to therapy by suppressing BAX and its activators. We report the discovery of BTSA1, a pharmacologically optimized BAX activator that binds with high affinity and specificity to the N-terminal activation site and induces conformational changes to BAX leading to BAX-mediated apoptosis. BTSA1-induced BAX activation effectively promotes apoptosis in leukemia cell lines and patient samples while sparing healthy cells...
October 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28986391/altered-hydroxymethylation-is-seen-at-regulatory-regions-in-pancreatic-cancer-and-regulates-oncogenic-pathways
#12
Sanchari Bhattacharyya, Kith Pradhan, Nathaniel Campbell, Jozef Mazdo, Aparna Vasantkumar, Shahina Maqbool, Tushar D Bhagat, Sonal Gupta, Masako Suzuki, Yiting Yu, John M Greally, Ulrich Steidl, James Bradner, Meelad Dawlaty, Lucy Godley, Anirban Maitra, Amit Verma
Transcriptional deregulation of oncogenic pathways is a hallmark of cancer and can be due to epigenetic alterations. 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification that has not been studied in pancreatic cancer. Genome-wide analysis of 5-hmC-enriched loci with hmC-seal was conducted in a cohort of low-passage pancreatic cancer cell lines, primary patient-derived xenografts, and pancreatic controls and revealed strikingly altered patterns in neoplastic tissues. Differentially hydroxymethylated regions preferentially affected known regulatory regions of the genome, specifically overlapping with known H3K4me1 enhancers...
November 2017: Genome Research
https://www.readbyqxmd.com/read/28900037/znf143-protein-is-an-important-regulator-of-the-myeloid-transcription-factor-c-ebp%C3%AE
#13
David Gonzalez, Annouck Luyten, Boris Bartholdy, Qiling Zhou, Miroslava Kardosova, Alex Ebralidze, Kenneth D Swanson, Hanna S Radomska, Pu Zhang, Susumu S Kobayashi, Robert S Welner, Elena Levantini, Ulrich Steidl, Gilbert Chong, Samuel Collombet, Min Hee Choi, Alan D Friedman, Linda M Scott, Meritxell Alberich-Jorda, Daniel G Tenen
The transcription factor C/EBPα is essential for myeloid differentiation and is frequently dysregulated in acute myeloid leukemia. Although studied extensively, the precise regulation of its gene by upstream factors has remained largely elusive. Here, we investigated its transcriptional activation during myeloid differentiation. We identified an evolutionarily conserved octameric sequence, CCCAGCAG, ∼100 bases upstream of the CEBPA transcription start site, and demonstrated through mutational analysis that this sequence is crucial for C/EBPα expression...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28684528/epigenetically-aberrant-stroma-in-mds-propagates-disease-via-wnt-%C3%AE-catenin-activation
#14
Tushar D Bhagat, Si Chen, Matthias Bartenstein, A Trevor Barlowe, Dagny Von Ahrens, Gaurav S Choudhary, Patrick Tivnan, Elianna Amin, A Mario Marcondes, Mathijs A Sanders, Remco M Hoogenboezem, Suman Kambhampati, Nandini Ramachandra, Iaonnis Mantzaris, Vineeth Sukrithan, Remi Laurence, Robert Lopez, Prafullla Bhagat, Orsi Giricz, Davendra Sohal, Amittha Wickrema, Cecilia Yeung, Kira Gritsman, Peter Aplan, Konrad Hochedlinger, Yiting Yu, Kith Pradhan, Jinghang Zhang, John M Greally, Siddhartha Mukherjee, Andrea Pellagatti, Jacqueline Boultwood, Britta Will, Ulrich Steidl, Marc H G P Raaijmakers, H Joachim Deeg, Michael G Kharas, Amit Verma
The bone marrow microenvironment influences malignant hematopoiesis, but how it promotes leukemogenesis has not been elucidated. In addition, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28405618/efficacy-of-alk5-inhibition-in-myelofibrosis
#15
Lanzhu Yue, Matthias Bartenstein, Wanke Zhao, Wanting Tina Ho, Ying Han, Cem Murdun, Adam W Mailloux, Ling Zhang, Xuefeng Wang, Anjali Budhathoki, Kith Pradhan, Franck Rapaport, Huaquan Wang, Zonghong Shao, Xiubao Ren, Ulrich Steidl, Ross L Levine, Zhizhuang Joe Zhao, Amit Verma, Pearlie K Epling-Burnette
Myelofibrosis (MF) is a bone marrow disorder characterized by clonal myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis, and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in ameliorating MF in patients. TGF-β family members are profibrotic cytokines and we observed significant TGF-β1 isoform overexpression in a large cohort of primary MF patient samples...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28292433/eto2-glis2-a-chimeric-transcription-factor-drives-leukemogenesis-through-a-neomorphic-transcription-network
#16
COMMENT
Justin C Wheat, Ulrich Steidl
Acute megakaryoblastic leukemia (AMKL) is a heterogeneous disease with a relatively poorly understood pathogenesis. In this issue of Cancer Cell, Thirant and colleagues systematically examine unique transcriptional and functional effects of ETO2-GLIS2, an oncogenic fusion protein frequently encountered in AMKL, and elucidate a therapeutic vulnerability in this poor-prognosis leukemia.
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28159737/stem-and-progenitor-cell-alterations-in-myelodysplastic-syndromes
#17
REVIEW
Aditi Shastri, Britta Will, Ulrich Steidl, Amit Verma
Recent studies have demonstrated that myelodysplastic syndromes (MDSs) arise from a small population of disease-initiating hematopoietic stem cells (HSCs) that persist and expand through conventional therapies and are major contributors to disease progression and relapse. MDS stem and progenitor cells are characterized by key founder and driver mutations and are enriched for cytogenetic alterations. Quantitative alterations in hematopoietic stem and progenitor cell (HSPC) numbers are also seen in a stage-specific manner in human MDS samples as well as in murine models of the disease...
March 23, 2017: Blood
https://www.readbyqxmd.com/read/27597933/dnmt3a-and-tet2-in-the-pre-leukemic-phase-of-hematopoietic-disorders
#18
REVIEW
Hanae Sato, Justin C Wheat, Ulrich Steidl, Keisuke Ito
In recent years, advances in next-generation sequencing (NGS) technology have provided the opportunity to detect putative genetic drivers of disease, particularly cancers, with very high sensitivity. This knowledge has substantially improved our understanding of tumor pathogenesis. In hematological malignancies such as acute myeloid leukemia and myelodysplastic syndromes, pioneering work combining multi-parameter flow cytometry and targeted resequencing in leukemia have clearly shown that different classes of mutations appear to be acquired in particular sequences along the hematopoietic differentiation hierarchy...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27392220/eliminating-cancer-stem-cells-in-cml-with-combination-transcriptional-therapy
#19
COMMENT
Luis A Carvajal, Ulrich Steidl
Leukemia stem cells (LSCs) are resistant to current therapies used to treat chronic myeloid leukemia (CML). Abraham et al. (2016) have identified a molecular network critical for CML LSC survival and propose that simultaneously targeting two of their major transcriptional regulators, p53 and c-Myc, may facilitate their eradication.
July 7, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27175029/targeted-positron-emission-tomography-imaging-of-cxcr4-expression-in-patients-with-acute-myeloid-leukemia
#20
Peter Herhaus, Stefan Habringer, Kathrin Philipp-Abbrederis, Tibor Vag, Carlos Gerngross, Margret Schottelius, Julia Slotta-Huspenina, Katja Steiger, Torben Altmann, Tanja Weißer, Sabine Steidle, Markus Schick, Laura Jacobs, Jolanta Slawska, Catharina Müller-Thomas, Mareike Verbeek, Marion Subklewe, Christian Peschel, Hans-Jürgen Wester, Markus Schwaiger, Katharina Götze, Ulrich Keller
Acute myeloid leukemia originates from leukemia-initiating cells that reside in the protective bone marrow niche. CXCR4/CXCL12 interaction is crucially involved in recruitment and retention of leukemia-initiating cells within this niche. Various drugs targeting this pathway have entered clinical trials. To evaluate CXCR4 imaging in acute myeloid leukemia, we first tested CXCR4 expression in patient-derived primary blasts. Flow cytometry revealed that high blast counts in patients with acute myeloid leukemia correlate with high CXCR4 expression...
August 2016: Haematologica
keyword
keyword
85082
1
2
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"