64th ASH Annual Meeting and Exposition: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Therapeutic Vulnerabilities Triggering Mechanisms of Drug Resistance and Sensitivity in Myeloid Neoplasms

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

Research, AML, Acute Myeloid Malignancies, Fundamental Science, apoptosis, Translational Research, Non-Biological therapies, Clinical Research, Combination therapy, drug development, Diseases, Therapies, metabolism, Biological Processes, Myeloid Malignancies, molecular biology

343-345 (Ernest N. Morial Convention Center)

Moderators:

Ami B. Patel, MD, University of Utah and Michele S. Redell, MD PhD, Baylor College of Medicine

Disclosures:

No relevant conflicts of interest to declare.

The Proposed Topic of the Session Delves in the Investigation of Mechanisms of Resistance and Sensitivity to Pharmacologic Agents or Epigenetic Factors. The Selected Studies Target Adult and Pediatric Populations.

9:30 AM

Epigenetic Resistance to Menin-MLL1 Inhibition Is Driven By Loss of the Non-Canonical Polycomb Repressive Complex 1.1 in NUP98-Rearranged AML

Emily B. Heikamp, MD, PhD¹^*, Jill A Henrich^1,2^*, Hannah E Rice¹^*, Sanisha Mahendra-Rajah¹^* and Scott A. Armstrong, MD, PhD¹

¹Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA
²University of Pennsylvania, Philadelphia, PA

9:45 AM

The Role of GATA2 in Drug Resistance in AML

Fatemeh Alikarami¹^*, Simone S. Riedel, PhD¹, Qinglan Li, Ph.D²^*, Changya Chen, Ph.D.³^*, Taylor Yamauchi⁴^*, Etienne Danis, PhD⁴^*, Kai Tan, PhD¹^*, Liling Wan, PhD², Tobias Neff⁴ and Kathrin M. Bernt, MD¹

¹Children's Hospital of Philadelphia, Philadelphia
²University of Pennsylvania, Philadelphia
³Children’s Hospital of Philadelphia, Philadelphia
⁴University of Colorado, Denver

10:00 AM

XPO1 Overexpression Is a Mechanism of Resistance to Eprenetapopt and 5-Azacitidine Therapy That Can be Therapeutically Exploited for the Treatment of TP53 Mutated Myeloid Malignancies

Traci L. Kruer, PhD¹, Ariel Quintana, PhD²^*, Meghan Ferrall-Fairbanks, PhD³, Ling Zhang, MD⁴^*, Hannah Newman, BS⁵^*, Amy F McLemore, M.S.⁶^*, Qin Yang, PhD⁷^*, Nana Bencrentsil, MD⁸, Rami S. Komrokji⁵, Sana Chaudhry, BS⁹^*, Tulasigeri M Totiger, PhD¹⁰^*, Maria Ken E. Figueroa, MD¹¹, Justin Taylor, MD¹², David A. Sallman, MD¹³ and Eric Padron, MD⁵

¹Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
²Malignant Hematology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
³J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL
⁴Department of Hematopathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
⁵Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL
⁶Malignant Hematology Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
⁷Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL
⁸H. Lee Moffitt Cancer Research Institute, Department of Malignant Hematology, Tampa, FL
⁹Sylvester Comprehensive Cancer Center, Miami
¹⁰Myeloma Division, Sylvester Comprehensive Cancer Center, University of Miami, Miami
¹¹Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL
¹²Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami, FL
¹³Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL

10:15 AM

Erythroid/Megakaryocytic Differentiation Confers BCL-XL Dependency and Venetoclax Resistance in Acute Myeloid Leukemia

Olli Dufva¹^*, Heikki Kuusanmäki, PhD^2,3, Markus Vaha-Koskela, PhD⁴^*, Aino-Maija Leppä, MSc(Tech)⁵^*, Jani Huuhtanen^6,7^*, Ida Vänttinen, MSc²^*, Petra Johanna Nygren¹^*, Jay Klievink, MSc¹^*, Jonas Bouhlal, BSc⁶^*, Petri Pölönen, PhD⁸^*, Qi Zhang, PhD⁹^*, Shady Adnan Awad, MD, PhD⁶^*, Cristina Mancebo¹⁰^*, Joseph Saad, MSc⁵^*, Juho J. Miettinen, PhD¹¹^*, Komal Kumar Javarappa, PhD¹², Sofia Aakko¹³^*, Tanja Ruokoranta, MSc²^*, Samuli Eldfors, PhD⁵, Merja Heinäniemi, PhD¹⁴^*, Ulla Wartiovaara-Kautto, MD, PhD¹⁵, Marina Konopleva, MD, PhD¹⁶, Mikko A Keränen, MD, PhD¹⁷^*, Kimmo Porkka, MD, PhD¹⁵^*, Krister Wennerberg^18,19^*, Mika Kontro, MD, PhD²⁰^*, Caroline A. Heckman, PhD⁵ and Satu Mustjoki, MD, PhD¹

¹Hematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
²Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
³Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark
⁴Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Finland, Helsinki, Finland
⁵Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
⁶Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
⁷Department of Computer Science, Aalto University School of Science, Espoo, Finland
⁸Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN
⁹Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX
¹⁰Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, Helsinki, Finland
¹¹University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, Helsinki, Finland
¹²Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Helsinki, Finland
¹³Institute of Molecular Medicine Finland (FIMM), Helsinki, Finland
¹⁴Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
¹⁵Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland
¹⁶Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX
¹⁷Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, Helsinki, Finland
¹⁸Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
¹⁹Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark
²⁰Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, Helsinki University Hospital Comprehensive Cancer Centre, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

10:30 AM

Simultaneous Inhibition of SIRT3 and Cholesterol Homeostasis Targets AML Stem Cells By Perturbing Fatty Acid β-Oxidation and Inducing Lipotoxicity

Cristiana O'Brien^1,2^*, Tianyi Ling¹^*, Jacob Berman²^*, Rachel Culp-Hill³^*, Julie A. Reisz⁴^*, Vincent Rondeau², Soheil Jahangiri⁵^*, Jonathan St-Germain, PhD²^*, Vinitha Macwan⁶^*, Audrey Astori⁵^*, Andy G.X. Zeng, BSc², Jun Young Hong, BS⁷^*, Meng Li, PhD⁸^*, Min Yang, PhD⁷^*, Sadhan Jana⁹^*, John E. Dick, PhD⁵, Hening Lin, PhD¹⁰^*, Ari Melnick, MD¹¹, Anastasia N Tikhonova, PhD^12,13, Andrea Arruda, MSc⁵^*, Mark D. Minden, MD, PhD^1,14, Brian Raught, PhD^1,2^*, Angelo D'Alessandro, PhD⁴ and Courtney L Jones, PhD^15,16

¹Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
²Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
³Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz School of Medicine, Aurora, CO
⁴Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO
⁵University Health Network, Toronto, ON, Canada
⁶University Health Network, Toronto, ON, CAN
⁷Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY
⁸Department of Medicine, Division of Hematology & Medical Oncology, Weill Cornell Medical College, New York, NY
⁹Cornell University, Ithaca, NY
¹⁰Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Cornell University, Ithaca, NY
¹¹Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY
¹²Department of Medical Biophysics, University of Toronto, Toronto, Canada
¹³Princess Margaret Cancer Research Centre, University Health Network, Toronto, ON, Canada
¹⁴Division of Medical Oncology and Hematology, University Health Network, Toronto, ON, Canada
¹⁵Princess Margaret Cancer Centre; University Health Network, Toronto, ON, Canada
¹⁶University of Toronto, Toronto, ON, Canada

10:45 AM

High Fatality CBFA2T3-GLIS2 Pediatric Acute Megakaryoblastic Leukemia Is Sensitive to BCL-X_L Inhibition

Verena Gress, MS¹^*, Mathieu Roussy²^*, Sophie Cardin, PhD²^*, Luc Boulianne²^*, Furat Fatima²^*, Louise Laramée²^*, Emma R. Cheetham²^*, Alexandre Rouette³^*, Nehme Hachem²^*, Véronique Lisi, PhD²^*, Azer Farah⁴^*, Melanie Bilodeau, PhD²^*, Frederic Barabe, MD⁵, Vincent-Philippe Lavallée, MD⁶^*, Brian T. Wilhelm, PhD, BSc⁷^* and Sonia Cellot, MD, PhD⁶

¹CHU Sainte-Justine Research Center, Montreal, QC, Canada
²CHU Sainte-Justine Research Center, Montréal, QC, Canada
³Integrated Centre for Pediatric Clinical Genomics, CHU Sainte-Justine Research Center, Montréal, QC, Canada
⁴The Leucegene project at Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, QC, Canada
⁵Centre intégré de cancérologie, CHU de Québec - Université Laval, Quebec, QC, Canada
⁶Department of Pediatric Hematology Oncology, CHU Sainte-Justine Research Center, Montréal, QC, Canada
⁷IRIC-University of Montreal, Montréal, QC, Canada

See more of: Oral and Poster Abstracts

<< Previous Session | Next Session >>

^*signifies non-member of ASH

604.O1.6 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Therapeutic Vulnerabilities Triggering Mechanisms of Drug Resistance and Sensitivity in Myeloid Neoplasms