64th ASH Annual Meeting and Exposition: 112. Thalassemia and Globin Gene Regulation I

Symposia: Thalassemia and Globin Gene Regulation Oral and Poster Abstracts
Oral

Research, Fundamental Science, clinical trials, Sickle Cell Disease, Acute Myeloid Malignancies, AML, adult, Translational Research, Clinical Research, Combination therapy, Thalassemia, Hemoglobinopathies, hematopoiesis, Diseases, Therapies, Biological Processes, Myeloid Malignancies, molecular biology, Study Population, Human

220-222 (Ernest N. Morial Convention Center)

Moderators:

Sujit Sheth, MD, Cornell University and Sherif M. Badawy, MD, Ann & Robert H. Lurie Children's Hospital of Chicago

Disclosures:

No relevant conflicts of interest to declare.

A mechanistic understanding of γ-globin silencing is of clinical importance as reversal of silencing in adult erythroid cells results in high level of hemoglobin F which is therapeutic in thalassemia. In this session, the first 4 presenters in this session describe the mechanism by which HIC2 expression is controlled during the developmental switch from fetal-to-adult hemoglobin production, locate the specific contacts driving the direct binding of ETO2 to NuRD, identify the obligate partner of BCL11A in silencing hemoglobin F and examined the role of individual Baf chromatin remodeling complex components in globin gene regulation. The two last abstracts summarize a subanalysis of Believe study evaluating the therapeutic effectiveness of luspatercept in patients with β0/β0 thalassemia and the effect of splenectomy on response to luspatercept and a combination therapy is explored in lab to increase response to luspatercept in beta thalassemia.

2:45 PM

799

Let-7 Inhibits HIC2 to Control BCL11A Transcription and Hemoglobin Switching

Peng Huang, PhD¹^*, Eugene Khandros, MD, PhD¹, Scott A. Peslak, MD, PhD^1,2, Cheryl A. Keller, PhD^3,4^*, Belinda M. Giardine⁴^*, Ross C. Hardison, PhD⁴^* and Gerd A. Blobel, MD, PhD¹

¹Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA
²Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
³Genomics Research Incubator, Pennsylvania State University, University Park, PA
⁴Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA

3:00 PM

800

ETO2 Recruitment of NuRD to the γ-Globin Locus Involves Multivalent Interaction with GATAD2A

David C. Williams, MD, PhD¹, Gage Oliver Leighton²^*, Parnika Agrawal²^*, Glory Dan-Dukor²^*, Shengzhe Shang³^* and Gordon Ginder, MD⁴

¹Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC
²University of North Carolina - Chapel Hill, Chapel Hill, NC
³Massey Cancer Center, Virginia Commonwealth University, Richmond
⁴Massey Cancer Center, Massey Cancer Center, Richmond, VA

3:15 PM

801

MBD2a-NuRD Binds to the γ-Globin Gene Promoter and Uniquely Forms a Complex Required for Bcl11a Mediated Silencing of Hb F Expression

Shengzhe Shang¹^*, Xia Li¹^*, Alexander Azzo²^*, Mikhail Dozmorov³^*, Tin Truong¹^*, Asit Manna⁴^*, David C. Williams, MD, PhD⁵ and Gordon Ginder, MD¹

¹Massey Cancer Center, Virginia Commonwealth University, Richmond
²School of Medicine, Virginia Commonwealth University, Richmond
³Bio-Statistics, Virginia Commonwealth University, Richmond
⁴Pathology, University of North Carolina, Chapel Hill
⁵Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC

3:30 PM

802

Examining the Role of Individual Baf Chromatin Remodeling Complex Components in Globin Gene Regulation

Kathryn M. Farrell¹^*, Peng Huang, PhD¹^*, Osheiza Y. Abdulmalik, DVM¹^*, Belinda M. Giardine²^*, Cheryl A. Keller, PhD²^*, Ross C. Hardison, PhD²^*, Junwei Shi, PhD³^*, Gerd A. Blobel, MD, PhD¹ and Eugene Khandros, MD, PhD¹

¹Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA
²Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA
³Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

3:45 PM

803

Combination of a TGF-β Ligand Trap (RAP-GRL) and TMPRSS6-ASO Is Superior for Correcting β-Thalassemia

Amaliris Guerra, PhD¹^*, Perry Demsko^2,3^*, Ariel Rivera³^*, Carlo Castruccio Castracani, PhD⁴^*, Laura Breda, PhD⁵^*, Naoto Tanaka⁴^*, Shuling Guo, PhD⁶^* and Stefano Rivella, PhD^2,7,8,9,10

¹Department of Pediatrics, Division of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, PA
²Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
³Children's Hospital Of Philadelphia, Philadelphia, PA
⁴Children's Hospital of Philadelphia, Philadelphia, PA
⁵The Children's Hospital of Philadelphia, Philadelphia, PA
⁶Ionis Pharmaceuticals, Inc., Carlsbad, CA
⁷Department of Pediatrics, Division of Hematology, Children’s Hospital of Philadelphia, Philadelphia, PA
⁸Cell and Molecular Biology affinity group (CAMB), University of Pennsylvania, Philadelphia, PA
⁹Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children’s Hospital of Philadelphia, Philadelphia, PA
¹⁰Penn Center for Musculoskeletal Disorders, University of Pennsylvania, Philadelphia, PA

4:00 PM

804

Effect of Luspatercept in β-Thalassemia Patients with β0/β0 Genotype: A Subgroup Analysis of the BELIEVE Study

Sujit Sheth, MD¹, Olivier Hermine, MD, PhD^2,3, Ali T. Taher, MD, PhD, FRCP⁴, Kevin H.M. Kuo, MD, MSc, FRCPC^5,6,7, John B. Porter, MD, FRCP, FRCPath⁸^*, Antonio Piga, MD⁹, Thomas D. Coates, MD^10,11, Antonis Kattamis, MD¹², Loyse Felber Medlin¹³^*, Wen-Ling Kuo¹⁴^*, Natalia Holot¹⁴^* and Maria Domenica Domenica Cappellini, MD¹⁵

¹Division of Pediatric Hematology/Oncology, Weill Cornell Medicine, New York, NY
²Department of Hematology, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
³Imagine Institute, INSERM U1163, University of Paris, Paris, France
⁴Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
⁵Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
⁶Division of Medical Oncology and Hematology, Department of Medicine, University Health Network, Toronto, ON, Canada
⁷Division of Hematology, Department of Medicine, University of Toronto, Toronto, ON, Canada
⁸University College London, University College London Hospitals, London, United Kingdom
⁹University of Turin, Turin, Italy
¹⁰Cancer and Blood Disease Institute, Children’s Hospital Los Angeles, Los Angeles, CA
¹¹USC Keck School of Medicine, Los Angeles, CA
¹²First Department of Pediatrics, National and Kapodistrian University of Athens, Athens, Greece
¹³Celgene International Sàrl, a Bristol-Myers Squibb Company, Boudry, Switzerland
¹⁴Bristol Myers Squibb, Princeton, NJ
¹⁵Fondazione IRCCS Ca’ Granda Policlinico Hospital, University of Milan, Milan, Italy

See more of: Oral and Poster Abstracts

<< Previous Session | Next Session >>

^*signifies non-member of ASH

112.O1.6 112. Thalassemia and Globin Gene Regulation I