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Fetal haemoglobin induction in sickle cell disease
Author(s) -
Paikari Alireza,
Sheehan Vivien A.
Publication year - 2018
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15021
Subject(s) - fetal hemoglobin , medicine , hydroxycarbamide , disease , haematopoiesis , clinical trial , hemoglobinopathy , immunology , stem cell , bioinformatics , fetus , biology , pregnancy , genetics
Summary 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 BCL 11A and HBS 1L ‐ MYB that are associated with HbF levels. Functional studies have established the roles of BCL 11A, MYB , and KLF 1 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.