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COMMENT
Koki Ueda, Ulrich Steidl
No abstract text is available yet for this article.
May 2021: Nature Cancer
#22
EDITORIAL
Justin C Wheat, Ulrich Steidl
No abstract text is available yet for this article.
February 3, 2022: Blood
#23
JOURNAL ARTICLE
Dörte Wichmann, Silvio Nadalin, Ulrich Schweizer, Wiebke Solaß, Christoph Steidle, Dietmar Stüker, Jessica Lange, Christoph R Werner, Alfred Königsrainer, Markus Quante
BACKGROUND: After intestinal transplantation, close allograft monitoring especially during the early postoperative period is crucial since the intestine is a highly immunogenic organ. Current protocols are based on endoscopic and histologic examination with the latter one being linked to the risk of bleeding and perforation. AIMS: Evaluation of the diagnostic value of endoscopy utilizing magnification to predict acute cellular rejection compared to routine allograft biopsies...
March 2022: Digestive and Liver Disease
#24
JOURNAL ARTICLE
Mansoor N Saleh, Manish R Patel, Todd M Bauer, Sanjay Goel, Gerald S Falchook, Geoffrey I Shapiro, Ki Y Chung, Jeffrey R Infante, Robert M Conry, Guilherme Rabinowits, David S Hong, Judy S Wang, Ulrich Steidl, Loren D Walensky, Gurudatta Naik, Vincent Guerlavais, Vojislav Vukovic, D Allen Annis, Manuel Aivado, Funda Meric-Bernstam
No abstract text is available yet for this article.
January 15, 2022: Clinical Cancer Research
#25
EDITORIAL
Goichi Tatsumi, Ulrich Steidl
No abstract text is available yet for this article.
October 21, 2021: Blood
#26
JOURNAL ARTICLE
Astha Thakkar, Zhu Cui, Stephen Zachary Peeke, Nishi Shah, Kith Pradhan, Amanda Lombardo, Fariha Khatun, Jennat Mustafa, Alyssa De Castro, Kailyn Gillick, Felisha Joseph, Anjali Naik, Shafia Rahman, Angelica D'Aiello, Richard Elkind, Susan Sakalian, Karen Fehn, Karen Wright, Michelly Abreu, Latoya Townsend-Nugent, Nicole Chambers, Rosmi Mathew, Donika Binakaj, Randin Nelson, Carlo Palesi, Monika Paroder, Joan Uehlinger, Yanhua Wang, Yang Shi, Xingxing Zang, Hao Wang, Christopher Nishimura, Xiaoxin Ren, Ulrich G Steidl, Kira Gritsman, Murali Janakiram, Noah Kornblum, Olga Derman, Ioannis Mantzaris, Aditi Shastri, Rachel Bartash, Yoram Puius, Margaret McCort, Mendel Goldfinger, Lizamarie Bachier-Rodriguez, Amit Verma, Ira Braunschweig, R Alejandro Sica
BACKGROUND: Adoptive immunotherapy using CD19-targeted Chimeric antigen receptor T cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data is limited on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy...
2021: Stem Cell Investigation
#27
JOURNAL ARTICLE
Teresa V Bowman, Catriona Jamieson, Ulrich Steidl, E Richard Stanley, Kira Gritsman, Denisa Wagner, Deepa Manwani, Andreas Trumpp, Toshio Suda, Keisuke Ito, Meelad Dawlaty, Daniel Lucas, Sandra Pinho
No abstract text is available yet for this article.
October 7, 2021: Cell Stem Cell
#28
JOURNAL ARTICLE
Teresa V Bowman, Catriona Jamieson, Ulrich Steidl, E Richard Stanley, Kira Gritsman, Denisa Wagner, Deepa Manwani, Andreas Trumpp, Toshio Suda, Keisuke Ito, Meelad Dawlaty, Daniel Lucas, Sandra Pinho
No abstract text is available yet for this article.
September 30, 2021: Cell
#29
JOURNAL ARTICLE
Teresa V Bowman, Catriona Jamieson, Ulrich Steidl, E Richard Stanley, Kira Gritsman, Denisa Wagner, Deepa Manwani, Andreas Trumpp, Toshio Suda, Keisuke Ito, Meelad Dawlaty, Daniel Lucas, Sandra Pinho
No abstract text is available yet for this article.
September 28, 2021: Developmental Cell
#30
JOURNAL ARTICLE
Nora E Rahmani, Nandini Ramachandra, Srabani Sahu, Nadege Gitego, Andrea Lopez, Kith Pradhan, Tushar D Bhagat, Shanisha Gordon-Mitchell, Bianca Rivera Pena, Mohammad Kazemi, Keshav Rao, Orsi Giricz, Shahina Bano Maqbool, Raul Olea, Yongmei Zhao, Jinghang Zhang, Hamid Dolatshad, Vickram Tittrea, Dharamveer Tatwavedi, Shalini Singh, Juseong Lee, Tianyu Sun, Ulrich Steidl, Aditi Shastri, Daichi Inoue, Omar Abdel-Wahab, Andrea Pellagatti, Evripidis Gavathiotis, Jacqueline Boultwood, Amit Verma
The BCL2-inhibitor, Venetoclax (VEN), has shown significant anti-leukemic efficacy in combination with the DNMT-inhibitor, Azacytidine (AZA). To explore the mechanisms underlying the selective sensitivity of mutant leukemia cells to VEN and AZA, we used cell-based isogenic models containing a common leukemia-associated mutation in the epigenetic regulator ASXL1. KBM5 cells with CRISPR/Cas9-mediated correction of the ASXL1G710X mutation showed reduced leukemic growth, increased myeloid differentiation, and decreased HOXA and BCL2 gene expression in vitro compared to uncorrected KBM5 cells...
September 21, 2021: Blood Cancer Journal
#31
COMMENT
Samuel J Taylor, Sriram Sundaravel, Ulrich Steidl
In this issue of Molecular Cell, Cao et al. (2021) report that AML cells are specifically addicted to an IRF8-MEF2D gene expression network. Furthermore, they identify a chromatin reader, ZMYND8, as the upstream regulator of the IRF8-MEF2D program whose activity is critical for AML cell survival.
September 2, 2021: Molecular Cell
#32
JOURNAL ARTICLE
Camila Prieto, Diu T T Nguyen, Zhaoqi Liu, Justin Wheat, Alexendar Perez, Saroj Gourkanti, Timothy Chou, Ersilia Barin, Anthony Velleca, Thomas Rohwetter, Arthur Chow, James Taggart, Angela M Savino, Katerina Hoskova, Meera Dhodapkar, Alexandra Schurer, Trevor S Barlowe, Ly P Vu, Christina Leslie, Ulrich Steidl, Raul Rabadan, Michael G Kharas
RNA binding proteins (RBPs) are key arbiters of post-transcriptional regulation and are found to be found dysregulated in hematological malignancies. Here, we identify the RBP RBMX and its retrogene RBMXL1 to be required for murine and human myeloid leukemogenesis. RBMX/L1 are overexpressed in acute myeloid leukemia (AML) primary patients compared to healthy individuals, and RBMX/L1 loss delayed leukemia development. RBMX/L1 loss lead to significant changes in chromatin accessibility, as well as chromosomal breaks and gaps...
July 2021: Nature Cancer
#33
REVIEW
Justin C Wheat, Ulrich Steidl
Nongenetic heterogeneity, or gene expression stochasticity, is an important source of variability in biological systems. With the advent and improvement of single molecule resolution technologies, it has been shown that transcription dynamics and resultant transcript number fluctuations generate significant cell-to-cell variability that has important biological effects and may contribute substantially to both tissue homeostasis and disease. In this respect, the pathophysiology of stem cell-derived malignancies such as acute myeloid leukemia and myelodysplastic syndromes, which has historically been studied at the ensemble level, may require reevaluation...
August 26, 2021: Blood
#34
JOURNAL ARTICLE
Mansoor N Saleh, Manish R Patel, Todd M Bauer, Sanjay Goel, Gerald S Falchook, Geoffrey I Shapiro, Ki Y Chung, Jeffrey R Infante, Robert M Conry, Guilherme Rabinowits, David S Hong, Judy S Wang, Ulrich Steidl, Gurudatta Naik, Vincent Guerlavais, Vojislav Vukovic, D Allen Annis, Manuel Aivado, Funda Meric-Bernstam
PURPOSE: We describe the first-in-human dose-escalation trial for ALRN-6924, a stabilized, cell-permeating peptide that disrupts p53 inhibition by mouse double minute 2 (MDM2) and MDMX to induce cell-cycle arrest or apoptosis in TP53-wild-type (WT) tumors. PATIENTS AND METHODS: Two schedules were evaluated for safety, pharmacokinetics, pharmacodynamics, and antitumor effects in patients with solid tumors or lymphomas. In arm A, patients received ALRN-6924 by intravenous infusion once-weekly for 3 weeks every 28 days; arm B was twice-weekly for 2 weeks every 21 days...
October 1, 2021: Clinical Cancer Research
#35
REVIEW
Emily Schwenger, Ulrich Steidl
Emerging clonal complexity has brought into question the way in which we perceive and, in turn, treat disorders of the hematopoietic system. Former models of cell-intrinsic clonal dominance driven by acquisition of driver genes in a stereotypic sequence are often insufficient in explaining observations such as clonal hematopoiesis, and new paradigms are in order. Here, we review the evidence within the hematologic malignancy field and also borrow from perspectives rooted in evolutionary biology to reframe pathogenesis of hematologic disorders as dynamic processes involving complex interplays of genetic and nongenetic subclones and the tissue microenvironment in which they reside...
May 2021: Cancer Discovery
#36
JOURNAL ARTICLE
Justin C Wheat, Ulrich Steidl
Non-genetic heterogeneity, or gene expression stochasticity, is an important source of variability in biological systems. With the advent and improvement of single molecule resolution technologies, it has been shown that transcription dynamics and resultant transcript number fluctuations generate significant cell-to-cell variability that has important biological effects and may contribute substantially to both tissue homeostasis and disease. In this respect, the pathophysiology of stem cell-derived malignancies such as AML and MDS, which has historically been studied at the ensemble level, may require re-evaluation...
June 22, 2021: Blood
#37
REVIEW
Emily Schwenger, Ulrich Steidl
Emerging clonal complexity has brought into question the way in which we perceive and, in turn, treat disorders of the hematopoietic system. Former models of cell-intrinsic clonal dominance driven by acquisition of driver genes in a stereotypic sequence are often insufficient in explaining observations such as clonal hematopoiesis, and new paradigms are in order. Here, we review the evidence both within the hematologic malignancy field and also borrow from perspectives rooted in evolutionary biology to reframe pathogenesis of hematologic disorders as dynamic processes involving complex interplays of genetic and non-genetic subclones and the tissue microenvironment in which they reside...
May 2021: Blood cancer discovery
#38
JOURNAL ARTICLE
Koki Ueda, Rajni Kumari, Emily Schwenger, Justin C Wheat, Oliver Bohorquez, Swathi-Rao Narayanagari, Samuel J Taylor, Luis A Carvajal, Kith Pradhan, Boris Bartholdy, Tihomira I Todorova, Hiroki Goto, Daqian Sun, Jiahao Chen, Jidong Shan, Yinghui Song, Cristina Montagna, Shunbin Xiong, Guillermina Lozano, Andrea Pellagatti, Jacqueline Boultwood, Amit Verma, Ulrich Steidl
MDMX is overexpressed in the vast majority of patients with acute myeloid leukemia (AML). We report that MDMX overexpression increases preleukemic stem cell (pre-LSC) number and competitive advantage. Utilizing five newly generated murine models, we found that MDMX overexpression triggers progression of multiple chronic/asymptomatic preleukemic conditions to overt AML. Transcriptomic and proteomic studies revealed that MDMX overexpression exerts this function, unexpectedly, through activation of Wnt/β-Catenin signaling in pre-LSCs...
April 12, 2021: Cancer Cell
#39
JOURNAL ARTICLE
Sriram Sundaravel, Ulrich Steidl, Amittha Wickrema
Erythroid differentiation program is comprised of lineage commitment, erythroid progenitor proliferation, and termination differentiation. Each stage of the differentiation program is heavily influenced by epigenetic modifiers that alter the epigenome in a dynamic fashion influenced by cytokines/humeral factors and are amicable to target by drugs. The epigenetic modifiers can be classified as DNA modifiers (DNMT, TET), mRNA modifiers (RNA methylases and demethylases) and histone protein modifiers (methyltransferases, acetyltransferases, demethylases, and deacetylases)...
January 2021: Seminars in Hematology
#40
JOURNAL ARTICLE
Iris Divé, Eike Steidl, Marlies Wagner, Katharina Filipski, Michael C Burger, Kea Franz, Patrick N Harter, Oliver Bähr, Emmanouil Fokas, Ulrich Herrlinger, Joachim P Steinbach
INTRODUCTION: Gliomatosis cerebri (GC) is defined by diffuse, widespread glial tumor growth affecting three or more cerebral lobes. Previous studies in gliomas found no distinct histological or molecular GC subtype, yet the presence of GC is associated with worse median overall survival (OS). Here, we explored whether differing therapeutic strategies in first-line treatment could account for this. METHODS: From our University Cancer Center database, 47 patients with histological diagnosis of WHO grade II or III glioma and GC imaging pattern were identified...
2021: Oncology
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