65th ASH Annual Meeting & Exposition: 602. Myeloid Oncogenesis: Basic: Mechanisms and Models of Myeloid Malignancy

Symposia: Myeloid Oncogenesis: Basic Oral and Poster Abstracts
Oral

Research, Fundamental Science, Acute Myeloid Malignancies, AML, MDS, Chronic Myeloid Malignancies, Diseases, Myeloid Malignancies, Biological Processes

Marriott Grand Ballroom 11-13 (Marriott Marquis San Diego Marina)

Moderators:

Chun-Wei David Chen, PhD, City of Hope and Juerg Schwaller, MD, University Hospital

Disclosures:

Schwaller: The Lundbeck Foundation: Consultancy.

The theme of this session is centered around novel models of myeloid malignancy. These approaches include mouse models of disease, engineering of human hematopoietic stem cells, and hybrid introduction of human genetic material into mouse cells. This session will explore research programs aimed at modeling mutation timing, sequential mutagenesis, and novel means for evaluating the necessity and sufficiency for common mutations in myeloid malignancies. The oral presentation in this session will offer new insights into the mechanisms by which common predisposing mutations, including STAG2 and DDX41, result in myeloid transformation.

4:30 PM

949

DDX41 Dissolves G-Quadruplexes to Maintain Erythroid Genomic Integrity and Prevent Genome DNA Leakage-Induced Cgas Activation

Honghao Bi, PhD¹, Pan Wang, Ph.D.¹^*, Wen Wang, Ph.D.²^*, Kehan Ren^1,3, Elizabeth Bartom, Ph.D.^3,4,5^*, Xu Han, PhD¹^*, Ermin Li, Ph.D.¹^* and Peng Ji, MD, PhD^1,3

¹Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL
²Center for Translational Neuroscience, University of Oregon, Eugene, OR
³Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
⁴Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL
⁵Department of Preventive Medicine/Division of Biostatistics, Feinberg School of Medicine, Northwestern University, Chicago, IL

4:45 PM

950

Fetal MLL-ENL Initiation Induces Developmental Stage-Specific Programs That Restrict Transformation and Depend on MLL3

Jonny Mendoza-Castrejon, BS¹, Emily B. Casey¹^*, Riddhi M. Patel¹^*, Elisabeth Denby¹^* and Jeffrey Magee, MD, PhD²

¹Department of Pediatrics, Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, MO
²Washington University School of Medicine, Saint Louis, MO

5:00 PM

951

Trisomy 8 Remodels Chromatin and Activates Transcription of Runx1-Target Genes in Hematopoietic Stem Cell

Jie Bai, PhD¹^*, Kimi Araki, PhD^2,3^*, Yasuhiro Kazuki, PhD⁴^*, Sho Kubota, PhD¹^*, Kenta Kikuchi, PhD⁵^*, Ai Hamashima¹^*, Mihoko Iimori¹^*, Supannika Sorin¹^*, Minetaro Ogawa, PhD⁶^*, Daisuke Kurotaki, PhD⁵^*, Mitsuo Oshimura, PhD⁷^* and Goro Sashida, MD, PhD¹

¹Laboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan
²Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan
³Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto, Japan
⁴Division of Genome and Cellular Functions, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Tottori, Japan
⁵Laboratory of Chromatin Organization in Immune Cell Development, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan
⁶Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan
⁷Chromosome Engineering Research Center, Tottori University, Tottori, Japan

5:15 PM

952

Pathogenic Mechanisms of DDX41 Mutations in the Development of Myeloid Malignancies

Ayana Kon¹^*, Masahiro Marshall Nakagawa, MD, PhD¹, Keisuke Kataoka, MD, PhD^2,3, Nobuyuki Kakiuchi, MD, PhD^1,4^*, Hideki Makishima, MD, PhD¹, Manabu Nakayama, MD, PhD⁵^*, Haruhiko Koseki, MD, PhD⁶^*, Yasuhito Nannya, MD, PhD^1,7 and Seishi Ogawa^1,8

¹Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
²Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
³Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo, Japan
⁴The Hakubi Center for Advanced Research, Kyoto University, Kyoto, Japan
⁵Chromosome Engineering Team, Department of Technology Development, Kazusa DNA Research Institute, Chiba, Japan
⁶Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
⁷Division of Hematopoietic Disease Control, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
⁸Center for Hematology and Regenerative Medicine, Department of Medicine (MedH), Karolinska Institutet, Huddinge, Sweden

5:30 PM

953

Engineering Sequential Mutations into Human HSPCs Yields an Aggressive Myeloid Malignancy Allowing for Interrogation of Preleukemic Transformation

Cailin T Collins^1,2,3, Yusuke Nakauchi, MD, PhD^1,3^*, Thomas Koehnke, MD^1,3, James S Chavez, BS^1,3^*, Suyoun Choi³^*, Rajiv Sharma, PhD³^*, Feifei Zhao^1,3^* and Ravi Majeti, MD^2,3,4

¹Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA
²Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA
³Cancer Institute, Stanford University School of Medicine, Stanford, CA
⁴Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA

5:45 PM

954

Synergy of Stag2-Cohesin Loss Results in Expansion of Npm1c-Mutant Hematopoietic Stem and Progenitor Cells

Jane J Xu, PhD^1,2^*, Yi Chen, MD, PhD³^*, John Pantazi³^*, Sebastian Fernando⁴^*, Besmira Alija³^*, Varun Sudunagunta, BA⁵, Govind Bhagat, MD⁶ and Aaron D. Viny, MD, MS⁷

¹Columbia University Irving Medical Center, Department of Medicine, Division of Hematology / Oncology, New York, NY
²Columbia Stem Cell Initiative, New York, NY
³Columbia Stem Cell Initiative, Columbia Irving Medical Centre, New York, NY
⁴Columbia Stem Cell Initiative, Columbia Irving Medical Centre, New York
⁵Columbia University Vagelos College of Physicians and Surgeons, NEW YORK, NY
⁶Department of Pathology, Columbia University Irving Medical Center, New York, NY
⁷Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY

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^*signifies non-member of ASH

602.O1.6 602. Myeloid Oncogenesis: Basic: Mechanisms and Models of Myeloid Malignancy