66th ASH Annual Meeting: 636. Myelodysplastic Syndromes: Basic and Translational: Disease Mechanisms and Therapeutic Vulnerabilities in Molecular Genetic Subtypes of MDS

Symposia: Myelodysplastic Syndromes: Basic and Translational Oral and Poster Abstracts
Oral

Research, Fundamental Science, Acute Myeloid Malignancies, AML, MDS, Acquired Marrow Failure Syndromes, Adult, Translational Research, CHIP, Bone Marrow Failure Syndromes, Inherited Marrow Failure Syndromes, Genomics, Bioinformatics, Chronic Myeloid Malignancies, Hematopoiesis, Diseases, Immunology, Computational biology, Myeloid Malignancies, Biological Processes, Emerging technologies, Molecular biology, Technology and Procedures, Gene editing, Study Population, Human, Pathogenesis

Ballroom 20CD (San Diego Convention Center)

Moderators:

Mikko Myllymäki, MD, PhD, and Carmelo Gurnari, MD, PhD, ARRAY(0xeaad838)

Disclosures:

Myllymäki: Gilead: Research Funding.

4:00 PM

343

Mis-Splicing Derived Neoantigens and Cognate T Cell Receptors in Splicing Factor Mutant Myeloid Neoplasms

Won Jun Kim¹^*, Edie I. Crosse, PhD²^*, Emma De Neef³^*, Inaki Etxeberria¹^*, Erich Sabio¹^*, Eric Wang, PhD⁴^*, Jan Philipp Bewersdorf, MD⁵, Sydney X. Lu⁶^*, Andrea Belleville³^*, Nina Fox¹^*, Cynthia Castro¹^*, Pu Zhang¹^*, Takeshi Fujino⁷^*, Jennifer Lewis⁷^*, Jahan Rahman⁸^*, Beatrice Zhang⁷^*, Jacob H. Winick¹^*, Alexander M. Lewis⁹^*, Robert Stanley, MD, PhD¹, Susan Dewolf, MD¹⁰^*, Brigita Meskauskaite Urben¹¹^*, Meril Takizawa¹¹^*, Tobias Krause¹²^*, Henrik Molina¹³^*, Ronan Chaligne, PhD¹⁴^*, Priya Koppikar¹⁵^*, Jeffrey J. Molldrem, MD¹⁶^*, Mathieu Gigoux¹⁷^*, Taha Merghoub¹⁸^*, Anthony F. Daniyan, MD¹⁹^*, Benjamin D. Greenbaum, PhD²⁰^*, Christopher A. Klebanoff, MD¹^*, Robert K. Bradley, PhD²¹^* and Omar Abdel-Wahab, MD²²

¹Memorial Sloan Kettering Cancer Center, New York
²Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA
³Fred Hutchinson Cancer Research Center, Seattle
⁴The Jackson Laboratory For Genomic Medicine, Farmington, CT
⁵Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
⁶Stanford University, Palo Alto
⁷Memorial Sloan Kettering Cancer Center, New York, NY
⁸Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, NY
⁹Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY
¹⁰Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY
¹¹Single-cell Analytics Innovation Lab, MSKCC, NEW YORK, NY
¹²Single-cell Analytics Innovation Lab, MSKCC, New York
¹³Rockefeller University, New York
¹⁴Single Cell Analytics and Innovation Lab, Memorial Sloan Kettering Cancer Center, New York, NY
¹⁵MD Anderson Cancer Center, Houston
¹⁶Department of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX
¹⁷McGill University, Montreal
¹⁸Weill Cornell Medical College, New York
¹⁹Department of Medicine, Cell Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY
²⁰Computational Oncology, Memorial Sloan Kettering Cancer Center, New York
²¹Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA
²²Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY

4:15 PM

344

MDS-Associated SF3B1 Mutations Promote Aberrant Hematopoietic Cell Fate Choice By Disrupting Mediator Kinase Module Component CDK8

Elizabeth Alice Bonner, BSc^1,2, Axia Song, MD²^*, Erica A Arriaga-Gomez, BSc²^*, Katherine Gadek, PhD³^*, Laura Baquero Galvis, BSc^1,4^*, Jonathan Linton, BA²^*, Rasika A Venkataraman, MSc^2,5,6, Sayantani Sinha, PhD²^*, Anthony Rongvaux, PhD^2,7^*, Myron Evans II, PhD³^*, Sergei Doulatov, PhD⁸ and Stanley C. Lee, PhD^9,10

¹Molecular and Cellular Biology Program, University of Washington School of Medicine, Seattle, WA
²Translational Science and Therapeutics Division, Fred Hutchison Cancer Center, Seattle, WA
³Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA
⁴Division of Hematology and Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA
⁵Molecular Medicine and Mechanism of Disease Program, University of Washington School of Medicine, Seattle, WA
⁶University of Washington, Department of Laboratory Medicine and Pathology, Seattle, WA
⁷Department of Immunology, University of Washington School of Medicine, Seattle, WA
⁸Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA
⁹Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA
¹⁰Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA

4:30 PM

345

Mitochondrial Transcriptional-Translational Conflict Contributes to Defective Erythropoiesis and Disease Progression in Splicing Factor Mutant Myelodysplastic Syndromes

Qiaoli Li, MD^1,2,3^*, Fei Yang^2,3,4^*, Yuanyi Ling^2,4^*, Zhen Gao^2,3,5^*, Hong Pan^2,3,6^*, Weiwang Li^2,3^*, Jingyu Zhao, MSc^2,3,5^*, Liwei Fang^2,3,5^*, Yajing Chu^2,7^*, Weiping Yuan^2,7 and Jun Shi, MD^2,5^*

¹State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology& Blood Diseases Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College, Tianjin, AL, China
²Tianjin Institutes of Health Science, Tianjin, China
³Red Blood Cell Diseases Center & Regenerative Medicine Clinic, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
⁴State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology& Blood Diseases Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College, Tianjin, China
⁵State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
⁶Red Blood Cell Diseases Center & Regenerative Medicine Clinic, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, AL, China
⁷State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, National Clinical Research Center for Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China

4:45 PM

346

Clonal Origin of Therapy-Related Myeloid Neoplasms after Autologous Stem Cell Transplant

Hidetaka Uryu, MD, PhD¹^*, Koichi Saeki²^*, Hiroshi Haeno³^*, Chiraag Kapadia, BA⁴, Ken Furudate, DMD, PhD⁵^*, Jyoti Nangalia, MBBChir⁶, Michael Spencer Chapman, MBBS⁷^*, Li Zhao⁸^*, Joanne Hsu, MD, PhD⁹^*, Chong Zhao¹⁰^*, Shujuan Chen¹¹^*, Tomoyuki Tanaka¹²^*, Zongrui Li¹²^*, Hui Yang, PhD, MD¹³, Courtney D. DiNardo, MD, MSc¹⁴, Naval Daver, MD¹⁵, Naveen Pemmaraju, MD¹⁶, Nitin Jain, MD⁵, Farhad Ravandi, MBBS¹⁷, Jianhua Zhang, PhD¹⁸^*, Xingzhi Song¹⁹^*, Erika Thompson²⁰^*, Hongli Tang²⁰^*, Latasha Little¹⁹^*, Curtis Gumbs²¹^*, Robert Z. Orlowski, MD, PhD^22,23, Muzaffar H. Qazilbash, MD²⁴, Kapil N. Bhalla, MD⁵, Simona Colla, PhD⁵, Hagop M. Kantarjian, MD⁵, Rashmi Kanagal-Shamanna, MD²⁵, Carlos E. Bueso-Ramos, MD, PhD²⁶, Daisuke Nakada, PhD²⁷, Jeffrey J. Molldrem, MD²⁸, Gheath Alatrash, PhD, DO²⁹, Andrew Futreal, PhD³⁰^*, Elizabeth J. Shpall, MD²⁴, Margaret Goodell, PhD^31,32, Guillermo Garcia-Manero, MD⁵ and Koichi Takahashi, MD, PhD⁵

¹Leukemia, The UNIVERSITY of TEXAS, M.D. Anderson, Houston, TX
²Division of Integrated Research,, Tokyo University of Science, Research Institute for Biomedical Sciences, Noda, Japan
³Division of Integrated Research, Tokyo University of Science, Research Institute for Biomedical Sciences, Noda, Japan
⁴Departments of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX
⁵Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
⁶Wellcome Sanger Institute, Hinxton, United Kingdom
⁷Wellcome Genome Campus, Wellcome Sanger Institute, Hinxton, United Kingdom
⁸Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
⁹Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston
¹⁰Departments of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston
¹¹Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
¹²Leukemia, MD Anderson Cancer Center, Houston, TX
¹³Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX
¹⁴Department of Leukemia, UT MD Anderson Cancer Center, Houston, TX
¹⁵MD Anderson Cancer Center, Houston, TX
¹⁶Department of Leukemia, The University of Texas MD Anderson Cancer Center, Bellaire, TX
¹⁷Department of Leukemia, University of Texas- MD Anderson Cancer Center, Houston, TX
¹⁸Departments of Genomic Medicine, M. D. Anderson Cancer Center, Houston, TX
¹⁹Departments of Genomic Medicine, MD Anderson Cancer Center, Houston, TX
²⁰Departments of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX
²¹Departments of Genomic Medicine, MD Anderson, Houston, TX
²²Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
²³Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
²⁴Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
²⁵Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
²⁶Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
²⁷Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX
²⁸Departments of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX
²⁹Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Pearland, TX
³⁰Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
³¹Department of Molecular Cell Biology, Baylor College of Medicine, Houston, TX
³²Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston

5:00 PM

347

Bi-Allelic DDX41 Mutations Exert Stage Specific Effects on Hematopoiesis to Promote Disease

Benjamin Kroger, BS¹, Yuanyuan Ji, PhD¹^*, Toby Thomas, BS¹^*, Yazan F Madanat, MD^1,2, Robert H. Collins, MD^1,2, Valeria Visconte, PhD³, Carmelo Gurnari, MD, PhD^4,5, Jaroslaw Maciejewski⁶ and Stephen Chung, MD^1,2,7

¹Division of Hematology/Oncology, Department of Internal Medicine, University of Texas Southwestern, Dallas, TX
²Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX
³Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Taussig Cancer Institute, Cleveland, OH
⁴Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
⁵Cleveland Clinic Foundation, Cleveland, OH
⁶Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH
⁷Children's Research Institute, University of Texas Southwestern, Dallas, TX

5:15 PM

348

Deficit of microRNA (miR)-142 Promotes Transformation of Clonal Myeloid Disorder into Acute Myeloid Leukemia (AML)

Yongfang Xu¹^*, Huafeng Wang^1,2^*, Fang Chen³^*, Jihyun Irizarry¹^*, Shawn Sharkas¹^*, Dandan Zhao¹^*, Mark Boldin⁴^*, Guido Marcucci¹ and Bin Zhang¹

¹Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA
²Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
³Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Monrovia, CA
⁴Department of Systems Biology, Beckman Research Institute of City of Hope, Duarte, CA

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^*signifies non-member of ASH

636.O1.6 636. Myelodysplastic Syndromes: Basic and Translational: Disease Mechanisms and Therapeutic Vulnerabilities in Molecular Genetic Subtypes of MDS