65th ASH Annual Meeting & Exposition: 631. Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational: Lineage Tracing and Novel Target Discovery

Symposia: Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational Oral and Poster Abstracts
Oral

Research, Fundamental Science, MDS, Translational Research, MPN, CML, Chronic Myeloid Malignancies, CMML, drug development, Diseases, Therapies, Myeloid Malignancies

Pacific Ballroom Salons 21-22 (Marriott Marquis San Diego Marina)

Moderators:

Linda Resar, MD, Johns Hopkins University SOM and Bethan Psaila, MD, PhD, University of Oxford

Disclosures:

No relevant conflicts of interest to declare.

This session covers how studying germline genetics, cooperating mutations and lineage tracing provides insights into pathobiology of MPNs, and the potential of mutant specific JAK inhibition.

2:45 PM

859

Cellular Barcoding of JAK2-V617F Hematopoietic Stem Cells Reveals No Substantial Preferences in the Contribution of Individual Stem Cell Clones to Erythroid Versus Megakaryocytic Lineages

Marc Usart¹^*, Tiago Almeida²^*, Julien Roux³^*, Athimed El Taher³^*, Riikka Karjalainen²^*, Quentin Kimmerlin⁴^*, Shivam Rai²^*, Hui Hao-Shen²^* and Radek C. Skoda, MD⁵

¹Department of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Basel-Stadt, Switzerland
²Department of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Switzerland
³University of Basel and University Hospital Basel, Basel, Switzerland
⁴Experimental Hematology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland, Basel, Switzerland
⁵Experimental Hematology, Department of Biomedicine, University Hospital and University, Basel, Switzerland

3:00 PM

860

Preclinical Evaluation of INCB160058 – a Novel and Potentially Disease-Modifying Therapy for JAK2V617F Mutant Myeloproliferative Neoplasms

Matthew C. Stubbs, PhD¹, Hamza Celik¹^*, Yanran Ai¹^*, Xin He¹^*, Hong Chang¹^*, Angela Lei¹^*, Mark Rupar¹^*, Brittney Wass¹^*, Melody Diamond¹^*, Xiaoming Wen¹^*, Jun Li¹^*, Nina Zolotarjova¹^*, Alex Margulis¹^*, Gaurang Trivedi¹^*, Angelo B.A. Laranjeira¹^*, Cooper A. Taylor¹^*, Jennifer Rocha¹^*, Christoph Pollmann²^*, Jacob Piehler²^*, Bianca L. Ferreira³^*, Ian Hitchcock³, Ricardo Macarrón¹, Eddy W. Yue¹^* and Sunkyu Kim¹^*

¹Incyte Research Institute, Wilmington, DE
²Osnabrück University, Osnabrück, Germany
³University of York, York, United Kingdom

3:15 PM

861

Cooperation between SF3B1 and JAK2^V617F Mutations Accelerates Fibrotic Progression in Myeloproliferative Neoplasms By Enhancing STAT1 Signaling

Jennifer O Sullivan^1,2^*, Sean Wen, BSc, MSc, PhD³^*, Affaf Aliouat⁴^*, Alba Rodriguez-Meira^5,6^*, Sally-Ann Clark, BSc, PhD⁷^*, Neil Ashley⁸^*, Amy Wood⁴^*, Ramy Slama⁴^*, Guanlin Wang⁹^*, Angela Hamblin, MD, PhD¹⁰^*, Lauren Murphy, BSc⁷^*, Christina Simoglou Karali⁷^*, Charlotte K Brierley, bmbch², Adam P Cribbs¹¹^*, Aimee Paterson⁴^*, Claire N Harrison¹², Bethan Psaila, MD, PhD¹³ and Adam J Mead, MRCP, FRCPath, PhD⁷

¹Dept of Haematology, Guys and St Thomas’ NHS Foundation Trust, London, United Kingdom
²Medical Research Council (MRC) Weatherall Institute of Molecular Medicine (WIMM) and NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom
³Haematopoietic Stem Cell Biology Laboratory, Medical Research Council Molecular Haematology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Cambridge, ENG, United Kingdom
⁴Weatherall Institute of Molecular Medicine, Oxford, United Kingdom
⁵Broad Institute of MIT and Harvard, Cambridge, MA
⁶Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA
⁷Medical Research Council (MRC) Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom
⁸Exact Sciences, Oxford, United Kingdom
⁹Fudan University, Institute of Metabolism and Integrative Biology,, Shanghai, China
¹⁰Cancer and Haematology Centre, The Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
¹¹Botnar Research Centre, Oxford, United Kingdom
¹²Guy’s and St. Thomas’ NHS Foundation Trust, London, ENG, United Kingdom
¹³Medical Research Council (MRC) Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, ENG, United Kingdom

3:30 PM

862

Nutrient-Sensitising Drug Repurposing Screen Identifies Lomerizine As a Mitochondrial Metabolism Inhibitor in Chronic Myeloid Leukaemia

Ahmed Khalaf, PhD¹^*, Lucie de Beauchamp, PhD¹^*, Eric Kalkman, PhD¹^*, Kevin Rattigan, PhD¹^*, Ekaterini Himonas¹^*, Joe Jones, PhD¹^*, Daniel James²^*, Engy Shokry Abd Shokry²^*, Mary Scott, PhD¹^*, Karen Dunn³^*, Saverio Tardito²^*, Mhairi Copland, PhD, MBBChir, FRCP, FRCPath³, David Sumpton, PhD²^*, Emma Shanks, PhD¹^* and Vignir Helgason, PhD¹

¹Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom
²Cancer Research UK Beatson Institute, Glasgow, United Kingdom
³Paul O’Gorman Leukaemia Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom

3:45 PM

863

Polygenic Germline Risk of Common Haematological Traits Drives Clonal Selection on JAK2^V617F and Development of Myeloproliferative Neoplasms

Jyoti Nangalia, MBBChir PhD¹^*, Jing Guo¹^*, Klaudia Walter¹^*, Pedro Quiros²^*, Muxin Gu²^*, E Joanna Baxter³^*, John Danesh⁴^*, Emanuele Di Angelantonio⁴^*, David Roberts⁴^*, Paola Guglielmelli, MD, PhD^5,6, Claire N Harrison⁷, Anna L Godfrey⁸^*, Anthony R Green⁹, George Vassiliou, FRCPath, MRCP, PhD, MBBS¹⁰, Dragana Vuckovic¹¹^* and Nicole Soranzo^12,13^*

¹Wellcome Sanger Institute, Hinxton, United Kingdom
²Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom
³Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
⁴University of Cambridge, National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, Cambridge, United Kingdom
⁵Centro Ricerca e Innovazione Malattie Mieloproliferative (CRIMM), AOU Careggi, Florence, Italy
⁶Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
⁷Guy’s and St. Thomas’ NHS Foundation Trust, London, ENG, United Kingdom
⁸Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom
⁹University of Cambridge, Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom
¹⁰Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
¹¹Imperial College London, London, United Kingdom
¹²Wellcome Trust Sanger Institute Wellcome Trust Genome Campus, Cambridge, United Kingdom
¹³Human Technopole, Milan, ITA

4:00 PM

864

TYK2 Is Essential for IFNα-Induced Resolution of MPN Features in a Murine Jak2V617F PMF Model

Yuki Tahira¹^*, Kotaro Shide, MD, PhD², Takuro Kameda, MD³, Ayako Kamiunten³^*, Keiichi Akizuki, MD⁴^*, Masayoshi Karasawa⁵^*, Ryoma Ikeda⁵^*, Kengo Matsumoto⁵^*, Yoko Kubuki, MD, PhD⁵^* and Kazuya Shimoda, MD, PhD³

¹Hematol., University of Miyazaki, Miyazaki, Japan, Miyazaki City, Japan
²Faculty of Medicine, Miyazaki Univ., Miyazaki, JPN
³University of Miyazaki, Miyazaki, Japan
⁴Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
⁵Division of Hematology, Diabetes, and Endcrinology University of Miyazaki, Miyazaki, JPN

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^*signifies non-member of ASH

631.O2.6 631. Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational: Lineage Tracing and Novel Target Discovery