Fetal haemoglobin induction in sickle cell disease
| Autor: | Alireza Paikari, Vivien A. Sheehan |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Genetic enhancement Genome-wide association study Anemia Sickle Cell Disease Biology Article Hydroxycarbamide 03 medical and health sciences Antisickling Agents hemic and lymphatic diseases Fetal hemoglobin medicine Animals Humans Fetal Hemoglobin Clinical Trials as Topic Genetic Therapy Hematology Clinical trial Haematopoiesis Treatment Outcome 030104 developmental biology Gene Expression Regulation Immunology Stem cell medicine.drug |
| Zdroj: | British Journal of Haematology. 180:189-200 |
| ISSN: | 0007-1048 |
| DOI: | 10.1111/bjh.15021 |
| Popis: | Fetal haemoglobin (HbF, α2γ2) induction has long been an area of investigation, as it is known to ameliorate the clinical complications of sickle cell disease (SCD). Progress in identifying novel HbF-inducing strategies has been stymied by limited understanding of gamma (γ)–globin regulation. Genome-wide association studies (GWAS) have identified variants in BCL11A and HBS1L-MYB that are associated with HbF levels. Functional studies have established the roles of BCL11A, MYB, and KLF1 in γ–globin regulation, but this information has not yielded new pharmacological agents. Several drugs are under investigation in clinical trials as HbF-inducing agents, but hydroxycarbamide remains the only widely used pharmacologic therapy for SCD. Autologous transplant of edited haematopoietic stem cells holds promise as a cure for SCD, either through HbF induction or correction of the causative mutation, but several technical and safety hurdles must be overcome before this therapy can be offered widely, and pharmacological therapies are still needed. |
| Databáze: | OpenAIRE |
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