Hemoglobin switching and its clinical implications.
Advances in the field of hemoglobin switching provide an excellent example of how the investigation of a biologic phenomenon may lead to the development of novel approaches for the treatment of disease. In patients with beta thalassemia and sickle cell disease, transcription switches from a normal gamma-globin gene, in the fetal stage of development, to an abnormal beta-globin gene, in the adult. Manipulations designed to achieve normal globin synthesis in patients with these disorders involve either a reversal of switching, with reestablishment of fetal hemoglobin synthesis, or the introduction of a normal exogenous globin gene to compensate for the defective endogenous gene. In this review we summarize how recent progress in understanding globin gene regulation has led to therapeutic interventions now under clinical investigation.
Blau
C A
CA
University of Washington, Seattle, USA.
Stamatoyannopoulos
G
G
D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood; D000818:Animals; D002986:Clinical Trials as Topic; D015536:Down-Regulation; D005319:Fetal Hemoglobin / Q000187:drug effects / Q000235:genetics; D005809:Genes, Regulator; D005812:Genes, Switch / Q000187:drug effects; D005914:Globins / Q000235:genetics; D006454:Hemoglobins / Q000235:genetics*; D006801:Humans; D017086:beta-Thalassemia / Q000097:blood
D006454:Hemoglobins; D005914:Globins; D005319:Fetal Hemoglobin