66th ASH Annual Meeting: 641. Chronic Lymphocytic Leukemia: Basic and Translational: CLL and Richter Transformation: Functional Genomics and Molecular Mechanisms

Symposia: Chronic Lymphocytic Leukemia: Basic and Translational Oral and Poster Abstracts
Oral

Research, Lymphoid Leukemias, Fundamental Science, Translational Research, CLL, Lymphomas, Non-Hodgkin lymphoma, CHIP, B Cell lymphoma, Genomics, Diseases, Immune mechanism, Aggressive lymphoma, Immunology, Lymphoid Malignancies, Metabolism, Biological Processes, Technology and Procedures, Gene editing, Pathogenesis

Pacific Ballroom Salons 15-17 (Marriott Marquis San Diego Marina)

Moderators:

Erika Tissino, PhD, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS and Dimitar G Efremov, MD, PhD, International Centre for Genetic Engineering and Biotechnology

Disclosures:

No relevant conflicts of interest to declare.

This session will include studies investigating CLL origin and driver function, including progression of CLL to Richter transformation. Mechanistic insights will be provided by new studies on patient-derived samples and murine models of disease. Novel insights into the role of clonal hematopoiesis in CLL and transformation will also be presented.

10:30 AM

757

Analysis of the Human CD5-Positive B-Cell Compartment As Cell-of-Origin of Chronic Lymphocytic Leukemia at Single-Cell Level

Cornelis A.M. van Bergen¹^*, Edwin Quinten, BS¹^*, Julieta Haydeé Sepulveda Yanez, MSc²^*, Ramin Monajemi, MSc³^*, Roberta Menafra, PhD⁴^*, Susan L. Kloet, PhD⁴^*, Szymon M. Kiełbasa, PhD³^* and Hendrik Veelken, MD, PhD ⁵

¹Hematology, Leiden University Medical Center, Leiden, Netherlands
²Leiden University Medical Center, Leiden, NLD
³Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
⁴Human Genetics, Leiden University Medical Center, Leiden, Netherlands
⁵Leiden University Medical Center, Leiden, Netherlands

10:45 AM

758

Impaired Response to Oxidative DNA Damage Underlies Genomic Instability in B-Cell Leukemia Driven By RPS15 Mutation

Marwan Kwok, MD, PhD, FRCPath, MRCP^1,2,3,4,5, Catherine Gutierrez, MD, PhD^1,2,3, Neil Ruthen¹^*, Peyton Waddicor^1,2^*, Tamara Ouspenskaia³^*, Christina Curran^1,6^*, Doris Fu^3,7^*, Binyamin Knisbacher, PhD^3,8, Anat Biran, PhD¹^*, Adi Nagler, PhD^1,2,3^*, Aviv Liani^1,6^*, Sarah Chen³^*, Gregory Lazarian, PharmD^1,9,10^*, Elizabeth Witten¹¹^*, Gabriela Brunsting Hoffmann¹^*, Emma Lin¹^*, Lucas Pomerance^1,2^*, Shuqiang Li, PhD^1,3,12^*, Lili Wang, MD, PhD^13,14, Kenneth J. Livak, PhD^1,12^*, Donna S. Neuberg, ScD¹⁵, Gad Getz, PhD^3,16,17^*, Elisa Ten Hacken, PhD^1,18 and Catherine J. Wu, MD^1,2,3^*

¹Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
²Harvard Medical School, Boston, MA
³Broad Institute of MIT and Harvard, Cambridge, MA
⁴Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom
⁵Centre for Clinical Haematology, Queen Elizabeth Hospital Birmingham, Birmingham
⁶Northeastern University, Boston, MA
⁷Massachusetts Institute of Technology, Cambridge, MA
⁸Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
⁹INSERM U978, Université Sorbonne Paris Nord, Bobigny, France
¹⁰Hematology Laboratory, Avicenne University Hospital, Assistance Publique – Hôpitaux de Paris, Bobigny, France
¹¹Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA
¹²Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA
¹³Department of Systems Biology, City of Hope Comprehensive Cancer Center, Duarte, CA
¹⁴Department of Systems Biology, City of Hope, Duarte, CA
¹⁵Department of Data Science, Dana-Farber Cancer Institute, Boston, MA
¹⁶Department of Pathology, Massachusetts General Hospital, Boston, MA
¹⁷Krantz Family Center for Cancer Research and Dept. of Pathology, Massachusetts General Hospital, Boston, MA
¹⁸Division of Hematology and Medical Oncology, Weill Cornell Medical College, Weill Cornell Medicine, New York City, NY

11:00 AM

759

Richter Syndrome-Associated Genetic Lesions in TP53 and the Cell Cycle Inhibitors CDKN2A and CDKN2B Induce Transformation of a CD5+ B Cell Subset Characterized By a Restricted IGHV Repertoire, Autoreactivity and BCR Dependence

Claudio Martines, PhD¹^*, Supriya Chakraborty, PhD¹^*, Giulia Felician, PhD¹^*, Karin Hofmann, MS¹^*, Sasha Blasutig, MS¹^*, Ivan Negara¹^*, Alice Bonato, PhD¹^*, Marija Vujovikj, MS²^*, Alberto Zamò, MD³^*, Andreas Rosenwald, MD⁴^*, Aleksandar J Dimovski, MD, PhD²^* and Dimitar G Efremov, MD, PhD⁵

¹Molecular Hematology, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy
²RCGEB, Macedonian Academy of Sciences and Arts, Skopje, MKD
³Institute of Pathology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany
⁴Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany
⁵Molecular Hematology, International Centre for Genetic Engineering and Biotechnology, Trieste, TS, Italy

11:15 AM

760

Integrating Metabolomics and Molecular Pathways to Uncover Therapeutic Vulnerabilities in Richter’s Transformation

Prajish Iyer, PhD¹, Brian Jiang²^*, Girish Venkataraman, MD, MBBS³, Joo Y. Song, MD⁴, Wing Chung Chan, MD⁵, Tanya Siddiqi, MD^6,7, Steven T. Rosen, MD^8,9, Alexey Danilov, MD, PhD^10,11, Antje Gohla¹²^* and Lili Wang, MD, PhD¹³

¹Department of Systems Biology, Beckman Research Institute, City of Hope National Comprehensive Cancer, Monrovia, CA
²Department of Systems Biology, Beckman Research Institute, City of Hope National Comprehensive Cancer, Monrovia
³Department of Pathology, University of Chicago, Chicago, IL
⁴Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
⁵Department of Pathology, City of Hope National Medical Center, Duarte, CA
⁶Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
⁷Toni Stephenson Lymphoma Center, Beckman Research Institute, Duarte
⁸City of Hope Comprehensive Cancer Center, Toni Stephenson Lymphoma Center, Beckman Research Institute, Duarte, CA
⁹Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope, Duarte, CA
¹⁰City of Hope Comprehensive Cancer Center, La Canada Flintridge, CA
¹¹Toni Stephenson Lymphoma Center, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA
¹²University of Wuerzburg, Wuerzburg, DEU
¹³Department of Systems Biology, City of Hope, Duarte, CA

11:30 AM

Identifying Novel Drug Vulnerabilities in Specified Molecular Subsets of Chronic Lymphocytic Leukemia

Salma Parvin, PhD¹^*, Binyamin Knisbacher, PhD², Aditi Aryal¹^*, Stacey M. Fernandes, BS³^*, Shlomi Medalion⁴^*, Guy Leib⁴^*, Johan Gustafsson, PhD⁵^*, Shir Amit⁴^*, Eden C Meidan⁴^*, Nadav Y Klein⁴^*, Savion Nafussy⁴^*, Donna S. Neuberg, ScD⁶, Catherine J. Wu, MD^3,5,7^*, Jennifer R. Brown, MD, PhD^7,8,9, Gad Getz, PhD^5,7,10,11^* and Anthony G. Letai^9,12

¹Dana Farber Cancer Institute, Boston, MA
²Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
³Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
⁴Bar-Ilan University, Ramat Gan, Israel
⁵Broad Institute of MIT and Harvard, Cambridge, MA
⁶Department of Data Science, Dana-Farber Cancer Institute, Boston, MA
⁷Harvard Medical School, Boston, MA
⁸Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
⁹Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA
¹⁰Department of Pathology, Massachusetts General Hospital, Boston, MA
¹¹Krantz Family Center for Cancer Research and Dept. of Pathology, Massachusetts General Hospital, Boston, MA
¹²Harvard Medical School, Boston

11:45 AM

762

Prevalence and Clinical Impact of Clonal Hematopoiesis of Indeterminate Potential (CHIP) in Chronic Lymphocytic Leukemia and Richter Transformation

Chiara Cosentino¹^*, Samir Mouhssine²^*, Mohammad Almasri¹^*, Ilaria Romano, MD^3,4, Lodovico Terzi Di Bergamo⁵^*, Jana Nabki²^*, Luca Cividini²^*, Bashar Al Deeban¹^*, Francesca Maiellaro¹^*, Abel Mehari Sium¹^*, Annalisa Gaglio⁶^*, Francesca Perutelli, MD⁷^*, Valentina Griggio⁷^*, Riccardo Dondolin, MD⁸^*, Matteo Bellia⁸^*, Silvia Rasi⁹^*, Eleonora Secomandi²^*, Sreekar Kogila¹^*, Joseph Ghanej²^*, Elisa Albi¹⁰^*, Candida Vitale, MD, PhD¹¹^*, Lydia Scarfo, MD^12,13, Paolo Ghia, MD, PhD^14,15, Marta Coscia, MD, PhD^11,16^*, Valter Gattei, MD¹⁷, Antonella Zucchetto, PhD¹⁷^*, Davide Rossi, MD, PhD¹⁸, Gianluca Gaidano, MD, PhD¹⁹ and Riccardo Moia, MD¹^*

¹Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
²Università Del Piemonte Orientale, Novara, ITA
³Institute of Oncology Research, Laboratory of Experimental Hematology, Bellinzona, Switzerland
⁴Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland, Bern, Switzerland
⁵Institute of Oncology Research, Bellinzona, CHE
⁶Clinical and Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
⁷A.O.U. Città della Salute e della Scienza di Torino e Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Università di Torino, Torino, Italy
⁸Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, ITA
⁹Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Novara, ITA
¹⁰Strategic Research Program on CLL, IRCCS Ospedale San Raffaele, Milano, Italy
¹¹Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino and Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy
¹²Università Vita Salute San Raffaele, Milano, Italy
¹³Division of Experimental Oncology, IRCCS Ospedale San Raffaele Milan Italy., Milano, Italy
¹⁴Università Vita-Salute San Raffaele, Milano, Italy
¹⁵Division of Experimental Oncology, B cell neoplasia, IRCCS Ospedale San Raffaele, Milan, Italy
¹⁶Hematology Division, ASST Sette Laghi, Ospedale di Circolo, Varese, Italy
¹⁷Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
¹⁸Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
¹⁹Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy

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^*signifies non-member of ASH

641.O2.6 641. Chronic Lymphocytic Leukemia: Basic and Translational: CLL and Richter Transformation: Functional Genomics and Molecular Mechanisms