65th ASH Annual Meeting & Exposition: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Personalized and Combinatorial Approaches to Target Vulnerabilities in Myeloid Malignancies

Symposia: Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms Oral and Poster Abstracts
Oral

Translational Research, Diseases, Therapies, Myeloid Malignancies

Ballroom 20CD (San Diego Convention Center)

Moderators:

Elvin Wagenblast, PhD, Icahn School of Medicine at Mount Sinai and Jennifer S. Carew, PhD, University of Arizona Cancer Center

Disclosures:

Carew: Majestic Therapeutics, LLC: Current equity holder in private company.

Identifying novel therapies, combination therapy approaches, and which patients will likely best respond to these therapies is essential to improving patient outcomes. In this session, novel therapeutic approaches for myeloid malignancies and potential strategies identify the optimal therapy for individual leukemia specimens will be discussed.

9:30 AM

Primary U2AF1^S34F Mutated Hematopoietic Cells Are Sensitive to Nonsense-Mediated RNA Decay Disruption In Vivo

Claudia Cabrera, BS¹, Sridhar N Srivatsan²^*, Abigael Cheruiyot³^*, Tanzir Ahmed⁴^*, Zheng Yang³^*, Jin Shao⁵^*, Monique Chavez, BS⁶^*, Sarah Grieb⁴^*, Julie Bailis, PhD⁷^*, Zhongsheng You, PhD³^* and Matthew J. Walter, MD⁸

¹Department of Medicine, Division of Oncology, Washington University School of Medicine, Saint Louis, MO
²Washington University in St. Louis, St. Louis, MO
³Department of Cell Biology and Physiology, Washington University in St.Louis, St. Louis
⁴Department of Medicine, Division of Oncology, Washington University in St.Louis, St. Louis
⁵Department of Medicine, Division of Oncology, Washington University School of Medicine, St Louis, MO
⁶Department of Medicine, Division of Oncology, Washington University In St. Louis School of Medicine, Saint Louis, MO
⁷Oncology Research, Amgen Inc, South Francisco, California Amgen, Inc, San Francisco
⁸Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO

9:45 AM

Altered RNA Export in SF3B1 Mutants Increases Sensitivity to Nuclear Export Inhibition

Sana Chaudhry, BS¹, Felipe Beckedorff, PhD²^*, Tulasigeri M Totiger, PhD¹^*, Maurizio Affer, MS¹^*, Nidhi Hariramani, MS³^*, Skye Montoya, BS¹, Alyssa Cornista, BS¹^*, Daniel Bilbao, PhD⁴, Evan R. Roberts, BS⁴^*, Jumana Afaghani, BS¹^*, Jose Antonio Rodríguez, PhD⁵^*, Eric Wang, PhD³ and Justin Taylor, MD⁶

¹Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
²Cancer Epigenetics Program, Sylvester Comprehensive Cancer Center, University of Miami-Miller School of Medicine, Miami, FL
³The Jackson Laboratory For Genomic Medicine, Farmington, CT
⁴Cancer Modeling Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
⁵Department of Genetics, University of the Basque Country (UPV/EHU), Leioa, Spain
⁶Sylvester Comprehensive Cancer Center, Miami, FL

10:00 AM

Synthetic Lethal Interactions with IRAK4 Inhibition in Myeloid Malignancies

Eric J Vick, MD, PhD^1,2, Josh Bennett, PhD³^*, Ashley E. Cochran, PhD¹^*, Kathleen Hueneman, MBA¹^*, Lyndsey C. Bolanos, MBA, BSc¹^*, Xiaohu Zhang⁴^*, Crystal McKnight⁴^*, Michele Ceribelli, PhD⁴^*, Carleen Klumpp-Thomas⁴^*, Kwangmin Choi, PhD¹^*, Kenneth Greis, PhD³^*, Craig J. Thomas, PhD⁴^* and Daniel T. Starczynowski, PhD^1,3

¹Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
²Division of Hematology/Oncology, University of Cincinnati, Cincinnati, OH
³University of Cincinnati College of Medicine, Cincinnati, OH
⁴Division of Pre-Clinical Innovation Chemistry Technologies, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD

10:15 AM

RSK1 Is an Exploitable Dependency in Myeloid Malignancies

Tim Kong, MSc¹, Angelo B. A. Laranjeira¹^*, LaYow Yu¹^*, Jared Scott Fowles, PhD¹^*, Daniel A.C. Fisher, PhD¹^*, Sherwin Ng²^*, Wei Yang, PhD³^*, Fan He, PhD¹, Maggie J Cox¹^*, Mary C. Fulbright¹^*, Stacey L. Rentschler, MD, PhD²^*, My-my Huynh, PhD⁴^*, Gerrit Los, PhD⁴^*, Sandra E. Dunn, PhD⁴^*, Grant A Challen, PhD⁵ and Stephen T. Oh, MD, PhD⁶

¹Division of Hematology, Department of Medicine, Washington University School of Medicine, St Louis, MO
²Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, MO
³Department of Genetics, Washington University School of Medicine, St. Louis, MO
⁴Phoenix Molecular Designs, Vancouver, BC, Canada
⁵Washington University School of Medicine In St. Louis, Saint Louis, MO
⁶Department of Medicine, Washington University School of Medicine, Saint Louis, MO

10:30 AM

SAMHD1 Inhibitor Combined with Immune Checkpoint Inhibitor Elicits an Anti-AML Immunity

Lei Zhang, MD¹^*, Haojie Dong, PhD²^*, Xin He, MD²^*, Amandeep Salhotra, MD³, Guido Marcucci, MD⁴, Yun Luo⁵^* and Ling Li, PhD²

¹Department of Hematological Malignancies Translational Science, City of Hope National Medical center, Monrovia
²Department of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
³Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
⁴Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
⁵College of Pharmacy, Western University of Health Sciences, Pomona

10:45 AM

Targeting Mitochondrial Apoptotic Priming State to Personalize Therapy for Relapsed Acute Myeloid Leukemia

Elyse Olesinski¹^*, Karanpreet Bhatia², Chuqi Wang³^*, Marissa Pioso^4,5^*, Shu Xuan Ng⁶^*, Xiao Xian Lin, BSc⁷^*, Vedant Sandhu⁶^*, Binyam Yilma¹^*, Stephan Rainer Maximilian Bohl, MD⁸^*, Jeremy Ryan¹^*, Disha Malani, PhD^1,9, Marlise R. Luskin, MD¹⁰, Olli Kallioniemi^11,12^*, Kimmo Porkka, MD, PhD¹³, Allen Yeoh, MD¹⁴^*, Sophia Adamia, PhD¹⁵, Wee Joo Chng, FRCP, FRCPath, PhD¹⁶^*, Motomi Osato¹⁷^*, David M. Weinstock, MD⁴, Jacqueline S. Garcia, MD¹⁸, Anthony G. Letai¹ and Shruti Bhatt, PhD¹⁹

¹Dana-Farber Cancer Institute, Boston, MA
²Winship Cancer Institute, Emory University, Atlanta
³Department of Pharmacy, National University of Singapore, Singapore, Singapore, SGP
⁴Dana Farber Cancer Institute, Boston, MA
⁵Harvard Medical School, Boston, MA, USA, Boston
⁶Department of Pharmacy, National University of Singapore, Singapore, Singapore, Singapore
⁷Department of Pharmacy, National University of Singapore, Singapore, SGP
⁸Dana-Farber Cancer Institute, Boston, MA, USA, Boston
⁹Harvard Medical School, Boston, MA
¹⁰Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
¹¹FIMM, University of Helsinki, Helsinki, Finland
¹²Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Stockholm, Sweden
¹³Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
¹⁴Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
¹⁵Dana-Farber Cancer Institute & HMS, Boston, MA
¹⁶National University Cancer Institute of Singapore, Singapore, SGP
¹⁷Kumamoto University, IRCMS, Kumamoto, JPN
¹⁸Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
¹⁹Department of Pharmacy, National University of Singapore, Singapore, Singapore

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^*signifies non-member of ASH

604.O3.6 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Personalized and Combinatorial Approaches to Target Vulnerabilities in Myeloid Malignancies