66th ASH Annual Meeting: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Uncovering New Targets and Disease Mechanisms in Myeloma

Symposia: Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational Oral and Poster Abstracts
Oral

Research, Fundamental Science, Adult, Translational Research, Assays, Plasma Cell Disorders, Genomics, Bioinformatics, Diseases, Immune mechanism, Lymphoid Malignancies, Metabolism, Computational biology, Biological Processes, Emerging technologies, Molecular biology, Technology and Procedures, Study Population, Human, Profiling, Animal model, Pathogenesis, Omics technologies

Pacific Ballroom Salons 24-26 (Marriott Marquis San Diego Marina)

Moderators:

Benjamin G. Barwick, PhD, Emory University and Linda B. Baughn, PhD,

Disclosures:

No relevant conflicts of interest to declare.

10:30 AM

763

Proteogenomic Screens Identify Plasma Cell Specific Vulnerabilities to Halt Oncogenic Transcription in Multiple Myeloma

Arnold Bolomsky¹^*, Smriti Kanangat¹^*, Michele Ceribelli, PhD²^*, Kristina Rinaldi¹^*, Lin Zhang¹^*, Elizabeth Hill, MD¹, Jagan R. Muppidi, MD, PhD¹^*, Craig J. Thomas, PhD²^* and Ryan M. Young, PhD¹^*

¹Lymphoid Malignancies Branch, National Institutes of Health, Bethesda, MD
²Division of Pre-Clinical Innovation Chemistry Technologies, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD

10:45 AM

764

PKMYT1 Kinase Is an Actionable Synthetically Lethal Target for Del17p Myeloma

Anais Schavgoulidze^1,2^*, Mariateresa Fulciniti, PhD³, Giulia Giorgetti, MS⁴^*, Sabrina Maheo⁵^*, Shuhui Deng⁶^*, Vanessa Favasuli, PhD⁷^*, Srikanth Talluri, PhD⁸^*, Masood A. Shammas, PhD⁸^*, Luka Pavageau⁹^*, Anil Aktas-Samur, PhD⁷^*, Mehmet K. Samur, PhD⁸, Herve Avet-Loiseau, MD, PhD¹⁰^*, Jill Corre, PharmD, PhD¹¹^* and Nikhil C. Munshi, MD¹²

¹Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA
²Toulouse Cancer Research Center-Oncopole, Toulouse University, INSERM UMR1037, Toulouse, France
³Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
⁴Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy
⁵IUCT, TOULOUSE, FRA
⁶State 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 Colleg, Tianjin, CHN
⁷Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
⁸Dana Farber Cancer Institute, Harvard Medical School, Boston, MA
⁹IUCT-Oncopole, Toulouse, FRA
¹⁰Institut universitaire du cancer de Toulouse Oncopole, Toulouse, France
¹¹Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France
¹²Dana-Farber Cancer Institute, Boston, MA

11:00 AM

765

The Mitochondrial Protease Clpp Is a Metabolic Vulnerability and an Immunogenic Trigger Against Multiple Myeloma

Tommaso Perini, MD, PhD^1,2^*, Paola Zordan³^*, Rossella Del Pizzo¹^*, Massimo Resnati¹^*, Ugo Orfanelli¹^*, Davide Stefanoni, PhD⁴^*, Laura Cassina⁵^*, Laura Oliva¹^*, Mehmet K. Samur, PhD⁶, Lisa Viviani¹^*, Maria Materozzi¹^*, Matteo Trudu¹^*, Alessandra Boletta⁵^*, Enrico Milan, PhD^1,7^*, Fabio Ciceri^2,7^*, Nikhil C. Munshi, MD⁸, Matteo Bellone, MD³^* and Simone Cenci, MD^4,7

¹Age Related Diseases Unit, Division of Genetics and Cell Biology, IRCCS Ospedale San Raffaele, Milan, Italy
²Hematology and Bone Marrow Transplantation Unit, IRCCS Ospedale San Raffaele, Milan, Italy
³Cellular Immunology Unit, Division of Immunology, Infectious Diseases and Transplantation, IRCCS Ospedale San Raffaele, Milan, Italy
⁴Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy
⁵Cystic Kidney Disorders Unit, Division of Genetics and Cell Biology, IRCCS Ospedale San Raffaele, Milan, Italy
⁶Dana Farber Cancer Institute, Harvard Medical School, Boston, MA
⁷Vita-Salute San Raffaele University, Milan, Italy
⁸Dana-Farber Cancer Institute, Boston, MA

11:15 AM

766

Whole Genome Sequencing Reveals Lower Apobec-Mutational Activity in Multiple Myeloma Patients with African Ancestry Compared with Those Having European Ancestry

Kylee H Maclachlan, PhD, BSc, FRACP, FRCPA¹, Marios Papadimitriou²^*, Patrick Blaney, MS³^*, Tala Shekarkhand, MS⁴^*, Timothy R. Chu, MS⁵^*, Alexandra Maria Poos, PhD⁶^*, Elizabeth Brown⁷^*, Antje Hoering, PhD⁸, Benjamin Diamond, M.D.⁹^*, Bachisio Ziccheddu¹⁰^*, Marc S. Raab, M.D.⁶^*, Niels Weinhold, PhD⁶^*, Ola Landgren¹¹, Faith E Davies, MD¹², Alexander M. Lesokhin, MD¹, Saad Z. Usmani, MD⁴, Francesco Maura, MD¹³ and Gareth Morgan, M.D., Ph.D.¹⁴^*

¹Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
²Myeloma Institute, Sylvester Comprehensive Cancer Center, University of Miami, Miami
³Myeloma Research Program, NYU Langone, Perlmutter Cancer Center, New York, NY
⁴Myeloma Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
⁵New York Genome Center, New York, NY
⁶Heidelberg Myeloma Center, Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany
⁷University of Alabama At Birmingham, Birmingham, AL
⁸Cancer Research And Biostatistics, Seattle, WA
⁹Sylvester Comprehensive Cancer Center, Myeloma Division, University of Miami, Miami, FL
¹⁰Myeloma Institute, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
¹¹Sylvester Comprehensive Cancer Center, Miami, FL
¹²NYU Perlmutter Cancer Center, NYU Langone Health, New York, NY
¹³University of Miami, Coral Gables, FL
¹⁴NYU Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY

11:30 AM

767

Single-Cell Multi-Omic Profiling of Patients with BCMA-Targeted Therapy Identifies Molecular and Cellular Factors Associated with Responsiveness and Treatment Effects

Minghao Dang, PhD¹^*, Hans C. Lee, MD¹, Hima Bansal, PhD²^*, Maria Acevedo-Calado, PhD¹^*, Li Qin, PhD¹^*, Wei Tan, PhD¹^*, Luz Yurany Moreno Rueda, PhD, MSc¹^*, David Berrios¹^*, Krina K. Patel, MD, MSc¹, Pei Lin, MD, DM, MDPC³, Sheeba K. Thomas, MD¹, Donna M. Weber, MD¹, Linghua Wang, MD, PhD, MS⁴^* and Robert Z. Orlowski, MD, PhD¹

¹Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
²Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
³Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
⁴Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

11:45 AM

768

Multiomics Data Integration in the Complete Myeloma Genome Reveals Frequent Centromeric Rearrangements and Their Epigenomic Consequences

Aneta Mikulasova, PhD¹^*, Enze Liu, PhD²^*, Nathan Becker, MS²^*, Parvathi Sudha²^*, Rafat Abonour, MD² and Brian A. Walker, PhD^2,3

¹Centre for Cancer and Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
²Melvin and Bren Simon Comprehensive Cancer Center, Division of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, IN
³Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN

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^*signifies non-member of ASH

651.O3.3 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Uncovering New Targets and Disease Mechanisms in Myeloma