Document Detail


Targeted therapeutic strategies for fetal hemoglobin induction.
MedLine Citation:
PMID:  22160074     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Increased levels of fetal hemoglobin (HbF) can ameliorate the severity of the β-hemoglobin disorders, sickle cell disease (SCD) and β-thalassemia, which are major sources of morbidity and mortality worldwide. As a result, there has been a longstanding interest in developing therapeutic approaches for inducing HbF. For more than 3 decades, the majority of HbF inducers developed were based on empiric observations and have had limited success. Recently, human genetic approaches have provided insight into previously unappreciated regulators of the fetal-to-adult hemoglobin switch and HbF silencing, revealing molecular targets to induce HbF. This article reviews these developments and discusses how molecules including BCL11A, KLF1, MYB, SOX6, miRNAs 15a and 16-1, and histone deacetylase 1 and 2 (HDAC1/2) could be important targets for HbF induction in humans. The current understanding of how these molecules function and the benefits and drawbacks of each of these potential therapeutic targets are also examined. The identification of these regulators of HbF expression is extremely promising and suggests that rationally designed approaches targeting the very mechanisms mediating this switching process could lead to better, less toxic, and more effective strategies for HbF induction.
Authors:
Vijay G Sankaran
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program     Volume:  2011     ISSN:  1520-4383     ISO Abbreviation:  Hematology Am Soc Hematol Educ Program     Publication Date:  2011  
Date Detail:
Created Date:  2011-12-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100890099     Medline TA:  Hematology Am Soc Hematol Educ Program     Country:  United States    
Other Details:
Languages:  eng     Pagination:  459-65     Citation Subset:  IM    
Affiliation:
1Children's Hospital Boston, Harvard Medical School, Boston, MA;
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