We have amplified and sequenced the 5' flanking and the second intervening sequence (IVS-II) regions of both the G gamma- and A gamma-globin genes of the beta S chromosomes from sickle cell anemia (SS) patients with homozygosities for five different haplotypes.
To determine whether the increased fetal hemoglobin production and/or elevated G gamma globin content are tightly linked to this haplotype, we studied 55 members of five Saudi families in which sickle cell disease is present.
Because butyrate and alpha-amino-n-butyric acid (ABA) augment gamma globin expression in normal neonatal and adult erythroid progenitors, we investigated the effects of sodium butyrate and ABA on erythroid progenitors of patients with beta thalassemia and sickle cell anemia who might benefit from such an effect.
Cloning and sequencing of the gamma-globin gene of a sickle cell anemia patient homozygous for the Bantu haplotype has revealed a gene conversion that involves the replacement of an A gamma sequence by a G gamma sequence in the promoter area of the A gamma gene.
Prenatal diagnosis of sickle cell anemia by restriction and endonuclease analysis: HindIII polymorphisms in gamma-globin genes extend test applicability.
However, the type of differences found and their distribution among haplotypes did not suggest that they represented distinctive changes that might explain the differential expression of the gamma-globin genes in sickle cell anemia.
A ribozyme-mediated approach has made it possible to replace the region in beta globin mRNA containing the sickle-cell-anaemia mutation with a gamma-globin-encoding sequence.
In practice, levels of developmental stage-discordant fetal gamma globin that can be achieved by using currently approved therapies are generally insufficient to fully resolve typical clincopathological features of sickle cell disease.
These results could have practical relevance, because pharmacologically mediated regulation of the expression of human gamma-globin genes, leading to increased HbF, is considered a potential therapeutic approach in haematological disorders, including beta-thalassaemia and sickle cell anaemia.
Exploring strategies for the design of artificial transcription factors: targeting sites proximal to known regulatory regions for the induction of gamma-globin expression and the treatment of sickle cell disease.
Lentiviral transduction of CD34(+) cells from patients with sickle cell anemia led to erythroid-specific expression of the gamma-globin transgene and concomitant reduction of endogenous beta(S) transcripts, thus providing proof of principle for therapeutic strategies that require synergistic gene addition and gene silencing in stem cell progeny.
In this review, we discuss the role of DNA methylation in gamma-globin gene regulation, describe clinical trials with agents that hypomethylate DNA and speculate about the future role of DNA hypomethylation therapy in patients with SCD and beta-thalassemia.
The developmental regulation of gamma-globin gene expression has shaped research efforts to establish therapeutic modalities for individuals affected with sickle cell disease (SCD).
Hence, therapeutic treatment of sickle cell anemia has been focused on introducing gamma-globin gene into red blood cells to increase the cellular gamma/beta(S) ratio.
Here, we genotyped additional BCL11A SNPs, HBS1L-MYB SNPs, and an SNP upstream of (G)gamma-globin (HBG2; the XmnI polymorphism), in two independent SCD cohorts: the African American Cooperative Study of Sickle Cell Disease (CSSCD) and an SCD cohort from Brazil.
A novel human gamma-globin gene vector for genetic correction of sickle cell anemia in a humanized sickle mouse model: critical determinants for successful correction.
These data could have practical relevance, because pharmacologically mediated regulation of human gamma-globin gene expression, with the consequent induction of fetal hemoglobin, is considered a potential therapeutic approach in hematological disorders including beta-thalassemia and sickle cell anemia.
Fetal hemoglobin (HbF), encoded by the HBG2 and HBG1 genes, is the best-known genetic modulator of sickle cell anemia, varying dramatically in concentration in the blood of these patients.