Fetal Hemoglobin Regulation in Beta-Thalassemia

Henry Y Lu; Stuart H Orkin; Vijay G Sankaran

doi:10.1016/j.hoc.2022.12.002

Fetal Hemoglobin Regulation in Beta-Thalassemia

Hematol Oncol Clin North Am. 2023 Apr;37(2):301-312. doi: 10.1016/j.hoc.2022.12.002.

Authors

Henry Y Lu¹, Stuart H Orkin², Vijay G Sankaran³

Affiliations

¹ Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Karp Family Research Laboratories, Boston Children's Hospital, 1 Blackfan Street, Boston, MA 02115, USA. Electronic address: https://twitter.com/realhenrylu.
² Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Karp Family Research Laboratories, Boston Children's Hospital, 1 Blackfan Street, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Harvard Stem Cell Institute, Cambridge, MA, USA.
³ Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Karp Family Research Laboratories, Boston Children's Hospital, 1 Blackfan Street, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA, USA. Electronic address: sankaran@broadinstitute.org.

PMID: 36907604
DOI: 10.1016/j.hoc.2022.12.002

Abstract

β-thalassemia is caused by mutations that reduce β-globin production, causing globin chain imbalance, ineffective erythropoiesis, and consequent anemia. Increased fetal hemoglobin (HbF) levels can ameliorate the severity of β-thalassemia by compensating for the globin chain imbalance. Careful clinical observations paired with population studies and advances in human genetics have enabled the discovery of major regulators of HbF switching (i.e. BCL11A, ZBTB7A) and led to pharmacological and genetic therapies for treating β-thalassemia patients. Recent functional screens using genome editing and other emerging tools have identified many new HbF regulators, which may improve therapeutic HbF induction in the future.

Keywords: Anemia; Beta-thalassemia; Fetal hemoglobin.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
DNA-Binding Proteins
Fetal Hemoglobin* / genetics
Humans
Transcription Factors
beta-Thalassemia* / genetics

Substances

Fetal Hemoglobin
DNA-Binding Proteins
Transcription Factors
ZBTB7A protein, human

Grants and funding

HHMI/Howard Hughes Medical Institute/United States