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The sympathomimetic agonist mirabegron did not lower JAK2-V617F allele burden, but restored nestin-positive cells and reduced reticulin fibrosis in patients with myeloproliferative neoplasms
Beatrice Drexler, Jakob R Passweg, Alexandar Tzankov, Martin Bigler, Alexandre Pa Theocharides, Nathan Cantoni, Peter Keller, Georg Stussi, Axel Ruefer, Rudolf Benz, Geneviève Favre, Pontus Lundberg, Ronny Nienhold, Andrea Fuhrer, Christine Biaggi, Markus G Manz, Mario Bargetzi, Simon Mendez-Ferrer, Radek C Skoda, Swiss Group for Clinical Cancer Research (SAKK)
Dec 13, 2018
The β-3 sympathomimetic agonist BRL37344 restored nestin-positive cells within the stem cell niche, and thereby normalized blood counts and improved myelofibrosis in a mouse model of JAK2-V617F-positive myeloproliferative...
BET protein inhibition shows efficacy against JAK2V617F-driven neoplasms.
BS Wyspiańska, AJ Bannister, I Barbieri, J Nangalia, A Godfrey, FJ Calero-Nieto, S Robson, I Rioja, J Li, M Wiese, E Cannizzaro, MA Dawson, B Huntly, RK Prinjha, AR Green, B Gottgens, T Kouzarides
Jun 13, 2014
Cohesin-dependent regulation of gene expression during differentiation is lost in cohesin-mutated myeloid malignancies.
Daniel Sasca, Haiyang Yun, George Giotopoulos, Jakub Szybinski, Theo Evan, Nicola K Wilson, Moritz Gerstung, Paolo Gallipoli, Anthony R Green, Robert Hills, Nigel Russell, Cameron S Osborne, Elli Papaemmanuil, Berthold Göttgens, Peter Campbell, Brian JP Huntly
Oct 03, 2019
Cohesin complex disruption alters gene expression, and cohesin mutations are common in myeloid neoplasia, suggesting a critical role in hematopoiesis. Here, we explore cohesin dynamics and regulation of hematopoietic stem cell...
Biomarkers Tumor Cell Cycle Proteins Cell Line Tumor Chromosomal Proteins Non-Histone Female Gene Dosage Gene Expression Regulation Leukemic Hematopoietic Stem Cells Histones Humans Male Mutation Myeloproliferative Disorders Neoplasm Grading Protein Binding Proto-Oncogene Proteins c-ets Regulatory Sequences Nucleic Acid Repressor Proteins
Hematopoietic Stem Cell Heterogeneity Is Linked to the Initiation and Therapeutic Response of Myeloproliferative Neoplasms.
Jingyuan Tong, Ting Sun, Shihui Ma, Yanhong Zhao, Mankai Ju, Yuchen Gao, Ping Zhu, Puwen Tan, Rongfeng Fu, Anqi Zhang, Ding Wang, Di Wang, Zhijian Xiao, Jiaxi Zhou, Renchi Yang, Stephen J Loughran, Juan Li, Anthony R Green, Emery H Bresnick, Dong Wang, Tao Cheng, Lei Zhang, Lihong Shi
Feb 24, 2021
The implications of stem cell heterogeneity for disease pathogenesis and therapy are poorly defined. JAK2V617F+ myeloproliferative neoplasms (MPNs), harboring the same mutation in hematopoietic stem cells (HSCs), display diverse...
Myeloproliferative neoplasms
Substantial progress has been made in our understanding of the pathogenetic basis of myeloproliferative neoplasms. The discovery of mutations in JAK2 over a decade ago heralded a new age for patient care as a consequence of...
Low-dose methotrexate in myeloproliferative neoplasm models.
Kavitha Chinnaiya, Michelle A Lawson, Sally Thomas, Marie-Therese Haider, Jenny Down, Andrew D Chantry, David Hughes, Antony Green, Jon R Sayers, John A Snowden, Martin P Zeidler
Nov 23, 2017
Myeloproliferative neoplasms – from origins to outcomes
Molecular determinants of pathogenesis and clinical phenotype in myeloproliferative neoplasms
The myeloproliferative neoplasms are a heterogeneous group of clonal disorders characterized by the overproduction of mature cells in the peripheral blood, together with an increased risk of thrombosis and progression to acute...
Clonal heterogeneity as a driver of disease variability in the evolution of myeloproliferative neoplasms.
Animals Cell Division Cell Transformation Neoplastic Clone Cells Cytokines Epigenesis Genetic evolution Molecular Gene Dosage Gene Knock-In Techniques Genetic Heterogeneity Hematopoietic Stem Cells Humans Janus Kinase 2 Leukemia Myeloid Models Genetic Multipotent Stem Cells Mutation Missense Myeloproliferative Disorders Neoplasm Proteins Neoplastic Stem Cells Phenotype Point Mutation RNA Splicing selection Genetic Signal Transduction Transcription Factors
The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance.
Monika Mortensen, Elizabeth J Soilleux, Gordana Djordjevic, Rebecca Tripp, Michael Lutteropp, Elham Sadighi-Akha, Amanda J Stranks, Julie Glanville, Samantha Knight, Sten-Eirik W Jacobsen, Kamil R Kranc, Anna Katharina Simon
Dec 21, 2018
The role of autophagy, a lysosomal degradation pathway which prevents cellular damage, in the maintenance of adult mouse hematopoietic stem cells (HSCs) remains unknown. Although normal HSCs sustain life-long hematopoiesis...
Classification and Personalized Prognosis in Myeloproliferative Neoplasms.
Jacob Grinfeld, Jyoti Nangalia, E Joanna Baxter, David C Wedge, Nicos Angelopoulos, Robert Cantrill, Anna L Godfrey, Elli Papaemmanuil, Gunes Gundem, Cathy MacLean, Julia Cook, Laura O'Neil, Sarah O'Meara, Jon W Teague, Adam P Butler, Charlie E Massie, Nicholas Williams, Francesca L Nice, Christen L Andersen, Hans C Hasselbalch, Paola Guglielmelli, Mary F McMullin, Alessandro M Vannucchi, Claire N Harrison, Moritz Gerstung, Anthony R Green, Peter J Campbell
Oct 03, 2018
Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal.
Mairi S Shepherd, Juan Li, Nicola K Wilson, Caroline A Oedekoven, Jiangbing Li, Miriam Belmonte, Juergen Fink, Janine CM Prick, Dean C Pask, Tina L Hamilton, Dirk Loeffler, Anjana Rao, Timm Schröder, Berthold Göttgens, Anthony R Green, David G Kent
Nov 01, 2018
JAK2V617F mediates resistance to DNA damage-induced apoptosis by modulating FOXO3A localization and Bcl-xL deamidation.
Apoptosis Cell Line Tumor DNA Damage Female Forkhead Box Protein O3 Gene Expression Regulation Neoplastic Hematopoietic Stem Cells Humans Janus Kinase 2 Male Mutation Myeloproliferative Disorders Neoplasms Phosphatidylinositol 3-Kinases Reactive Oxygen Species Sodium-Hydrogen Exchangers bcl-X Protein
Continuous Indexing of Fibrosis (CIF)
Hosuk Ryou, Korsuk Sirinukunwattana, Alan Aberdeen, Gillian Grindstaff, Bernadette J Stolz, Helen Byrne, Heather A Harrington, Nikolaos Sousos, Anna L Godfrey, Claire N Harrison, Bethan Psaila, Adam J Mead, Gabrielle Rees, Gareth DH Turner, Jens Rittscher, Daniel Royston
Feb 09, 2023
The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to...
Zinc-dependent multimerization of mutant calreticulin is required for MPL binding and MPN pathogenesis.
Jeanne F Rivera, April J Baral, Fatima Nadat, Grace Boyd, Rachael Smyth, Hershna Patel, Emma L Burman, Ghadah Alameer, Sally A Boxall, Brian R Jackson, E Joanna Baxter, Peter Laslo, Anthony R Green, David G Kent, Ann Mullally, Edwin Chen
Apr 09, 2021
Calreticulin (CALR) is mutated in the majority of JAK2/MPL-unmutated myeloproliferative neoplasms (MPNs). Mutant CALR (CALRdel52) exerts its effect by binding to the thrombopoietin receptor MPL to cause constitutive activation...
Results of a national UK physician reported survey of COVID-19 infection in patients with a myeloproliferative neoplasm.
Richard A Salisbury, Natalia Curto-Garcia, Jennifer O'Sullivan, Frederick Chen, Paolo Polzella, Anna L Godfrey, James Russell, Steven Knapper, John Willan, Rebecca Frewin, Shivani Joshi, Siamak Arami, Sarah Burns, Chun Huat Teh, Frances Wadelin, Jaymathi Dhanapal, Pratap Neelakantan, Dragana Milojkovic, Beth Psaila, Richard Szydlo, Sebastian Francis, Catherine Cargo, Manish Jain, Andrew McGregor, Louise Wallis, Andrew Duncombe, Hayder Hussein, Peter Dyer, Laura Munro, Lee Bond, Mary Frances McMullin, Tim CP Somervaille, Mamta Garg, Mallika Sekhar, Claire Harrison, Adam J Mead, Andrew J Innes
Jul 30, 2021
Mutant CALR functions
In this issue of Blood, Shide et al separate the roles of loss of a normal CALR
allele and gain of a mutant CALR allele in CALR-driven essential thrombocythemia (ET).
Ruxolitinib-induced defects in DNA repair cause sensitivity to PARP inhibitors in myeloproliferative neoplasms.
Margaret Nieborowska-Skorska, Silvia Maifrede, Yashodhara Dasgupta, Katherine Sullivan, Sylwia Flis, Bac Viet Le, Martyna Solecka, Elizaveta A Belyaeva, Lucia Kubovcakova, Morgan Nawrocki, Martin Kirschner, Huaqing Zhao, Josef T Prchal, Katarzyna Piwocka, Alison R Moliterno, Mariusz Wasik, Steffen Koschmieder, Tony R Green, Radek C Skoda, Tomasz Skorski
May 31, 2018
Myeloproliferative neoplasms (MPNs) often carry JAK2(V617F), MPL(W515L), or CALR(del52) mutations. Current treatment options for MPNs include cytoreduction by hydroxyurea and JAK1/2 inhibition by ruxolitinib, both of which are...
Inhibition of interleukin-1β reduces myelofibrosis and osteosclerosis in mice with JAK2-V617F driven myeloproliferative neoplasm.
Shivam Rai, Elodie Grockowiak, Nils Hansen, Damien Luque Paz, Cedric B Stoll, Hui Hao-Shen, Gabriele Mild-Schneider, Stefan Dirnhofer, Christopher J Farady, Simón Méndez-Ferrer, Radek C Skoda
Oct 15, 2022
Interleukin-1β (IL-1β) is a master regulator of inflammation. Increased activity of IL-1β has been implicated in various pathological conditions including myeloproliferative neoplasms (MPNs). Here we show that IL-1β serum levels...