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An α-chain modification rivals the effect of fetal hemoglobin in retarding the rate of sickle cell fiber formation.

ABSTRACT: Adults with sickle cell disease bear a mutation in the β-globin gene, leading to the expression of sickle hemoglobin (HbS; α₂β^S₂). Adults also possess the gene for γ-globin, which is a component of fetal hemoglobin (HbF, α₂γ₂); however, γ-chain expression normally ceases after birth. As HbF does not form the fibers that cause the disease, pharmacological and gene-modifying interventions have attempted to either reactivate expression of the γ chain or introduce a gene encoding a modified β chain having γ-like character. Here, we show that a single-site modification on the α chain, αPro114Arg, retards fiber formation as effectively as HbF. Because this addition to the repertoire of anti-sickling approaches acts independently of other modifications, it could be coupled with other therapies to significantly enhance their effectiveness.

SUBMITTER: Worth EH

PROVIDER: S-EPMC10713580 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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An α-chain modification rivals the effect of fetal hemoglobin in retarding the rate of sickle cell fiber formation.

Worth Eli H EH Fugate Mark K MK Grasty Kimberly C KC Loll Patrick J PJ Bishop Marilyn F MF Ferrone Frank A FA

Scientific reports 20231211 1

Adults with sickle cell disease bear a mutation in the β-globin gene, leading to the expression of sickle hemoglobin (HbS; α2βS2). Adults also possess the gene for γ-globin, which is a component of fetal hemoglobin (HbF, α2γ2); however, γ-chain expression normally ceases after birth. As HbF does not form the fibers that cause the disease, pharmacological and gene-modifying interventions have attempted to either reactivate expression of the γ ...[more]

PMID: 38081985

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Fetal hemoglobin modulates neurocognitive performance in sickle cell anemia✰,✰✰.

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