ASH 2021: spotlight on St. Jude research at the American Society of Hematology annual meeting

Presentations from St. Jude scientists

Allogeneic hematopoietic cell transplantation is increasingly being used in patients with sickle cell disease, and researchers are looking at cerebral blood flow to evaluate success. Akshay Sharma, MBBS, of the Department of Bone Marrow Transplantation and Cellular Therapy, will present reduced intensity hematopoietic cell transplantation improves cerebral hemodynamics in children with sickle cell disease  December 11. 

In research to better understand the underlying biology of myeloproliferative disorders, Johanna Melo-Cardenas, PhD, from the laboratory of John Crispino, PhD, Division of Experimental Hematology director, will present how IL13 contributes to fibrotic progression of myeloproliferative neoplasms  December 11.

Swati Naik, MBBS, of the Department of Bone Marrow Transplantation and Cellular Therapy, will discuss transplantation for pediatric cancer, specifically how CD45RA-depleted haploidentical transplantation combined with natural killer cell addback results in promising long-term outcomes in pediatric patients with high-risk hematologic malignancies December 11.

In another December 11 session, researchers will share their findings on new treatments for pediatric acute lymphoblastic leukemia (ALL). Chunliang Li, PhD, of the Department of Tumor Cell Biology, will present interrogating novel bromodomain inhibition resistance mechanisms in MLL-rearranged leukemia.

Another ALL treatment will be shared by Jianzhong Hu, from the laboratory of Jun J. Yang, PhD, of the Department of Pharmacy and Pharmaceutical Sciences, on the development of proteolytic targeting chimeras to target Lck in T cell acute lymphoblastic leukemia. Also from the Yang lab, Yizhen Li, PhD, will present the impact of T cell immunity on chemotherapy response in childhood acute lymphoblastic leukemia. Both talks occur December 13.

Also in ALL, Brennan Bergeron, a student in the St. Jude Graduate School of Biomedical Sciences, will discuss research from the Pharmaceutical Sciences laboratory of Daniel Savic, PhD. Mapping the gluococorticoid gene regulatory network and alterations that contribute to steroid resistance in childhood acute lymphoblastic leukemia will be presented December 13. 

Two December 13 presentations from the laboratory of Mitchell Weiss, MD, PhD, Department of Hematology chair, will explore aspects of the biology of blood cells. Ruopeng Feng, Ph.D., will discuss the regulation of fetal hemoglobin expression by the VHL-HIF1a oxygen sensing system  and Senthil Bhoopalan, MBBS, PhD, will present a novel RPS19-edited hematopoietic stem cell model of Diamond-Blackfan anemia for the development of a lentiviral vector gene therapy. Bhoopalan has received an ASH Abstract Achievement Award for this study.  

Gene therapy is an emerging approach for treating sickle cell disease; however, information about the knowledge and feelings of patients about this therapy is lacking. Liza-Marie Johnson, MD, Department of Oncology, will present research on  December 13 that addresses this through patient and caregiver attitudes toward gene therapy for sickle cell disease: A need for partnership and education.

Bringing together the worlds of sickle cell disease and HPV vaccination efforts, clinical fellow Tarun Aurora, MD, will present successful HPV vaccination in adolescents with sickle cell disease following a quality improvement bundle intervention, in collaboration with Jane Hankins, MD, Department of Hematology, also December 13. 

Late-breaking abstract session

The ASH annual meeting includes a selection of abstracts of research projects completed after the ASH 2021 deadline, but which the program committee recognizes as exciting and of high impact. 

Research from Masayuki Umeda, Ph.D., in the laboratory of Jeffery Klco, MD, PhD, Department of Pathology, will be presented December 14 as a late-breaking abstract looking at the molecular basis of relapse in a type of pediatric leukemia. The work covers how an integrated genomic analysis identifies UBTF tandem duplications as a subtype-defining lesion in pediatric acute myeloid leukemia.

Sessions moderated by St. Jude investigators

December 11, Paulina Velasquez, MD, Department of Bone Marrow Transplantation and Cellular Therapy, will moderate the cellular immunotherapies: basic and translational 1  session; Ilaria Iacobucci, PhD, Department of Pathology, will moderate emerging diagnostic tools and techniques: WGS and WTS: the new gold standard in hematology; and Shannon McKinney-Freeman, PhD, and Wilson Clements, PhD, both of the Department of Hematology, will co-moderate hematopoietic stem and progenitor cells and hematopoiesis: basic and translational: development and aging. 

Moderating December 13 will be Akshay Sharma in a session on hemoglobinopathies, excluding thalassemia: basic and translational emerging strategies to identify and prevent sickle cell disease pathology.

Workshops and special sessions

Marcin Wlodarski, MD, PhD, Department of Hematology, organized a scientific workshop on germline predisposition to hematopoietic malignancies and bone marrow failure. He will moderate and present opening remarks. During this December 10 workshop, Richa Sharma, MD, Department of Hematology, will moderate a session on DNA repair and malignancy. Additionally, Sara Lewis, Department of Hematology, will discuss a registry for individuals with germline SAMD9 and SAMD9L mutations; and Senthil Bhoopalan presents TP53-dependent hematopoietic stem cell defects in RPS19 gene-edited CD34+ cells. 

Other workshops featuring St. Jude researchers include: Shengdar Tsai, PhD, Department of Hematology, on genotoxicities associated with genome editing, including sickle cell disease; Jonathan Yen, PhD, Department of Hematology, on base editing for sickle cell disease; and Shannon McKinney-Freeman, on murine fetal bone marrow and how it does not support functional hematopoietic stem and progenitor cells until birth. 

Also December 10, Esther Obeng, MD, PhD, Department of Oncology, will speak as part of the trainee activities and services session on the ASH Harold Amos Medical Faculty Development Program. In a December 13 special-interest session on gene editing and real-world data, Jane Hankins will present a report and recommendations for the coordinated registry network work group. 

Early-career investigators receive recognition

This year, two St. Jude investigators received the ASH Research Training Award for Fellows.  Senthil Bhoopalan and Richa Sharma, MD, both of the Department of Hematology, were individually recognized with the award that is designed to encourage junior researchers in hematology or hematology/oncology to pursue careers in the field. 

Also in 2021, Aimee Talleur, MD, Department of Bone Marrow Transplantation and Cellular Therapy, received an ASH Scholar Award. The award helps investigators who have completed their training and have research experience work as independent scientists.

Poster Presentations

Poster abstracts are available online.

Session 113. Hemoglobinopathies, Excluding Thalassemia: Basic and Translational: Poster II

• 2027 Association of Thrombospondin-1 Gene Polymorphism with Elevated Tricuspid Regurgitant Velocity in Sickle Cell Anemia; Parul Rai, MD, MBBS, Hematology
  
• 2030 Social Determinants of Health and Neurocognitive Functioning in Sickle Cell Disease; Andrew M Heitzer, PhD, Psychology
  

Session 114. Hemoglobinopathies, Excluding Thalassemia: Clinical and Epidemiological: Poster III

• 3110 Assessment of Cardiac Abnormalities in Sickle Cell Disease Patients Using Cardiac Magnetic Resonance Imaging (CMR); Cara Morin, MD, PhD

Session 401. Blood Transfusion: Poster II

• 2145 Retrospective Review of Transfusion Practices in a Single Neonatal Intensive Care Unit (NICU) Compared to Recent Transfusion Guidelines ; Jasmine Smith, MD, Hematology/Oncology

Session 602. Disordered Gene Expression and Epigenetics in Hematologic Malignancies: Basic: Poster III

• 3304 Amino Acid Stress Response Genes Promote L-Asparaginase Resistance in Pediatric Acute Lymphoblastic Leukemia. Daniel Ferguson, PhD, Pharmaceutical Sciences
• 2215 Chromatin Accessibility Landscapes of Acute Lymphoblastic Leukemia;  Kelly R. Barnett, PhD, Hematological Malignancies Program and Center for Precision Medicine in Leukemia

Session 613. Acute Myeloid Leukemias: Clinical and Epidemiological: Poster II

• 2295 Clinical Features and Cytoreduction Therapy in Children with Newly Diagnosed Acute Myeloid Leukemia and Hyperleukocytosis; Georgios E. Christakopoulos, MD, Oncology

Session 618. Acute Lymphoblastic Leukemias: Biomarkers, Molecular Markers and Minimal Residual Disease in Diagnosis and Prognosis: Poster III

• 3476 The Impact of Genetic Ancestry on the Biology and Prognosis of Childhood Acute Lymphoblastic Leukemia. Shawn Lee, MD, Pharmaceutical Sciences
  

Session 703. Cellular Immunotherapies: Basic and Translational: Poster II

• 2782 CD19-CAR T Cells Develop Exhaustion Epigenetic Programs during a Clinical Response; Caitlin C. Zebley, MD, PhD, Bone Marrow Transplantation and Cellular Therapy
  

Session 711. Cell Collection and Processing: Poster I

• 1770 Optimization of Autologous Hematopoietic Progenitor Stem Cell Apheresis Collection from Plerixafor-Mobilized Patients with Sickle Cell Disease;  Yan Zheng, MD, PhD, Pathology
  

Session 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster II

• 2854 Exposure to Anti-Anaerobic Antimicrobials Around Hematopoietic Cell Transplant (HCT) Is Associated with Poor Outcomes in Pediatric Patients; Jamie Truscott, MD, Bone Marrow Transplantation and Cellular Therapy
  

Session 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster II

• 2897 CD45RO+ T-Cell Add Back and Prophylactic Blinatumomab Administration Post Tcrαβ/CD19-Depleted Haploidentical Transplantation in Pediatric Patients with High Risk Acute Leukemia;  Swati Naik, MBBS
  

Session 901. Health Services Research—Non-Malignant Conditions: Poster II

• 2992 Impact of Gaps in Care during Adult Care Transfer in Sickle Cell Disease; Kristen E Howell, PhD, MPH, Psychology