64th ASH Annual Meeting and Exposition: 631. Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational: Identification of Novel Therapeutic Targets in MPN and CML

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

Research, Fundamental Science, Biological therapies, Antibody Therapy, adult, Translational Research, MPN, Non-Biological therapies, CML, Combination therapy, genomics, Chronic Myeloid Malignancies, hematopoiesis, Diseases, immune mechanism, Therapies, metabolism, Adverse Events, computational biology, Myeloid Malignancies, Biological Processes, molecular biology, Technology and Procedures, gene editing, Study Population, Human, pathogenesis, machine learning, omics technologies

275-277 (Ernest N. Morial Convention Center)

Moderators:

Anna E Marneth, PhD, Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School and Bethan Psaila, MD, PhD, MRC Molecular Haematology Unit

Disclosures:

Psaila: Novartis: Consultancy, Honoraria, Speakers Bureau; Galecto: Research Funding; Blueprint Therapeutics: Consultancy; Evotec: Research Funding; Alethiomics: Consultancy, Current equity holder in private company, Honoraria, Other: Co-founder , Research Funding; Constellation Therapeutics: Consultancy.

In this session, mechanistic insights into the pathogenesis of MPN and CML will be revealed which represent molecular vulnerabilities of the MPN or CML inducing hematopoietic stem cells. This includes the discovery of a monoclonal antibody which specifically targets mutant Calreticulin in MPN. Single cell RNA sequencing, CRISPR screens and drug profiling led to the identification of novel therapeutic targets which were validated in pre-clinical models.

4:00 PM

325

A Single-Cell Atlas Identifies Pretreatment Features of Primary Imatinib Resistance in Chronic Myeloid Leukemia

Vaidehi Krishnan, PhD¹^*, Florian Schmidt²^*, Zahid Nawaz²^*, Kian Leong Lee¹^*, Prasanna Nori Venkatesh²^*, Meera Makheja²^*, Zhu En Chan¹^*, Mengge Yu³^*, Nirmala Arul Rayan²^*, Michelle Gek Liang Lim²^*, Alice Cheung, PhD⁴, Sudipto Bari, PhD⁵^*, John Ouyang⁶^*, Owen Rackham⁶^*, Tuan Zea Tan, Ph.D⁷^*, William YK Hwang, MBBS⁸, Charles Chuah, MD⁹^*, Shyam Prabhakar²^* and Sin Tiong Ong, MD^1,4,10

¹Cancer & Stem Cell Biology Programme, DUKE-NUS Medical School, Singapore, Singapore
²Genome Institute of Singapore, Singapore, Singapore
³Cancer & Stem Cell Biology Programme, Duke-NUS Medical School, Singapore, Singapore
⁴Singapore General Hospital, Singapore, Singapore
⁵National Cancer Centre, Singapore, Singapore
⁶DUKE-NUS Medical School, Singapore, Singapore
⁷Cancer Science Institute of Singapore, Singapore, Singapore
⁸Department of Hematology, Singapore General Hospital, Singapore, Singapore
⁹Singapore General Hospital, Duke-NUS Medical School, Singapore, Singapore
¹⁰Duke University Medical Center, Durham, NC

4:15 PM

326

JAK Inhibition Mediates Clonal Selection of RAS Pathway Mutations in Myeloproliferative Neoplasms

Nabih Maslah, PharmD, PhD^1,2^*, Blandine Roux, MSc³^*, Nina Kaci, MSc³^*, Emmanuelle Verger, PhD^1,2^*, Rafael Daltro De Oliveira, MD⁴^*, Hélène Pasquer, MSc^3,4^*, Nicolas Gauthier, MD⁴^*, Juliette Soret, MD⁴^*, Saravanan Ganesan²^*, Panhong Gou, PhD²^*, Frank Ling, MSc³^*, Nathalie Parquet, MD⁵^*, William Vainchenker, MD, PhD⁵^*, Emmanuel Raffoux⁵^*, Rose Ann Padua, PhD², Stephane Giraudier, MD PhD^1,2^*, Alexandre Puissant, PhD³, Camille Lobry, PhD³^*, Jean-Jacques Kiladjian, MD^2,4, Bruno Cassinat, PharmD, PhD^1,2 and Lina Benajiba, MD, PhD^3,4

¹Laboratoire de Biologie Cellulaire, Université Paris Cité, APHP, Hôpital Saint-Louis, Paris, France
²INSERM UMR 1131, Institut de Recherche Saint-Louis, Paris, France
³INSERM UMR 944, Institut de Recherche Saint-Louis, Paris, France
⁴Centre d’Investigations Cliniques, INSERM CIC 1427, Université Paris Cité, APHP, Hôpital Saint-Louis, Paris, France
⁵Département d’hématologie et d’Immunologie, Université Paris Cité, APHP, Hôpital Saint-Louis, Paris, France

4:30 PM

327

Dual Targeting of HDM2 and PPM1D As a Novel Therapeutic Approach for Myelofibrosis

Bridget K Marcellino, MD, PhD¹, Cara Clementelli, MS²^*, Kristin Beaumont, PhD³^*, Christoph Schaniel, PhD²^*, Min Lu, PhD, MD⁴, Karie Chen, MS²^*, Adena Russel²^*, Ayman Mohammad²^*, Daniel I Nathan, MD²^*, Jake Aronin²^*, Alan H. Shih, MD, PhD², Robert Sebra, PhD³^* and Ronald Hoffman, MD^2,5

¹Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY
²Tisch Cancer Institute, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY
³Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY
⁴Tisch Cancer Institute, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, Elmhurst, NY
⁵MPN Research Consortium, New York, NY

4:45 PM

328

Integrated High-Throughput Drug Profiling and CRISPR Screening Identify Novel Pathway Vulnerabilities of Leukemic Stem Cells in Chronic Myeloid Leukemia

Shady Adnan Awad, MD, PhD^1,2^*, Olli Dufva^3,4^*, Jay Klievink, MSc^3,5^*, Ella Karjalainen, MSc⁶^*, Aleksandr Ianevski⁷^*, Paavo Pietarinen, PhD³^*, Daehong Kim, PhD³^*, Swapnil Potdar, MSc⁸^*, Maija Wolf, PhD⁸^*, Kourosh Lotfi, MD⁹^*, Tero Aittokallio, PhD⁷^*, Krister Wennerberg^10,11^*, Kimmo Porkka, MD, PhD^3,12,13^* and Satu Mustjoki, MD, PhD^1,14,15

¹Translational Immunology Research program and Department of Clinical Chemistry and Hematology, University of Helsinki, Helsinki, Finland
²Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
³Hematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
⁴Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
⁵Translational Immunology Research program, University of Helsinki, Helsinki, Finland
⁶Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Finland, Helsinki, Finland
⁷Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
⁸Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
⁹Department of Hematology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
¹⁰Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark
¹¹Institute for Molecular Medicine Finland, University of Helsinki, University of Helsinki, Finland
¹²HUS Comprehensive Cancer Center, Hematology Research Unit Helsinki and iCAN Digital Precision Cancer Center Medicine Flagship, University of Helsinki, Helsinki, Finland
¹³Helsinki University Central Hospital Cancer Center, Helsinki, Finland
¹⁴iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
¹⁵Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, Helsinki, Finland

5:00 PM

329

The High Mobility Group A1 Chromatin Regulator Drives Immune Evasion during MPN Progression By Repressing Genes Involved in Antigen Presentation

Joseph Kim, BS^1,2, Jung-Hyun Kim, PhD¹, Leslie Cope, PhD³^*, Liping Li, MD, PhD¹^*, Raajit K Rampal, MD, PhD⁴, Richard Koche, PhD⁴^*, Jerry L. Spivak, MD^1,3, Alison R. Moliterno, MD¹ and Linda Resar, MD^1,2,3,5

¹Department of Medicine, Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD
²Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD
³Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
⁴Human Oncology and Pathogenesis Program, Leukemia Service, Department of Medicine, Center for Epigenetics, Memorial Sloan Kettering Cancer Center, New York, NY
⁵Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD

5:15 PM

330

Jak2^V617F Reversible Activation Shows an Essential Requirement for Jak2^V617F in Myeloproliferative Neoplasms (MPNs)

Andrew Dunbar, MD¹, Robert L. Bowman, PhD², Young Park, MS³^*, Franco Izzo, PhD⁴, Robert M. Myers⁵, Abdul Karzai, BS³^*, Won Jun Kim³^*, Inés Fernández Maestre³^*, Michael R. Waarts⁶^*, Abbas Nazir³^*, Wenbin Xiao, MD, PhD⁷, Max Brodsky, MD⁸, Mirko Farina, MD⁹^*, Louise Cai⁶^*, Sheng F Cai, MD, PhD¹⁰, Benjamin Wang¹¹^*, Wenbin An⁶^*, Julie Yang, PhD¹²^*, Shoron Mowla⁶^*, Shira E. Eisman⁶^*, Tanmay Mishra⁶^*, Remie Houston³^*, Emily Guzzardi, BA³^*, Anthony R. Martinez Benitez, BA³^*, Aaron D Viny, MD, MS¹³, Richard Koche, PhD¹²^*, Dan A. Landau, MD, PhD¹⁴ and Ross L. Levine, MD⁶

¹Department of Medicine and Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY
²Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA
³Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY
⁴Meyer Cancer Center & Institute of Computational Biomedicine, Weill Cornell Medicine, New York City, NY
⁵Tri-Institutional MD-PhD Program, Weill Cornell Medicine, Rockefeller University, Memorial Sloan Kettering Cancer Center, New York, NY
⁶Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY
⁷Department of Pathology and Laboratory Medicine, Hematopathology Service, Memorial Sloan Kettering Cancer Center, New York, NY
⁸Department of Medicine, Johns Hopkins University, Baltimore, MD
⁹Unit of Blood Diseases and Stem Cell Transplantation, ASST Spedali Civili, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Pavia, Italy
¹⁰Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY
¹¹Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York
¹²Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY
¹³Columbia Stem Cell Initiative, Columbia University, New York, NY
¹⁴Meyer Cancer Center & Institute of Computational Biomedicine, Weill Cornell Medicine, New York, NY

See more of: Oral and Poster Abstracts

<< Previous Session | Next Session >>

^*signifies non-member of ASH

631.O1.6 631. Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational: Identification of Novel Therapeutic Targets in MPN and CML