Sickle Cell Anemia and Its Phenotypes

Annu Rev Genomics Hum Genet. 2018 Aug 31:19:113-147. doi: 10.1146/annurev-genom-083117-021320. Epub 2018 Apr 11.

Abstract

In the 100 years since sickle cell anemia (SCA) was first described in the medical literature, studies of its molecular and pathophysiological basis have been at the vanguard of scientific discovery. By contrast, the translation of such knowledge into treatments that improve the lives of those affected has been much too slow. Recent years, however, have seen major advances on several fronts. A more detailed understanding of the switch from fetal to adult hemoglobin and the identification of regulators such as BCL11A provide hope that these findings will be translated into genomic-based approaches to the therapeutic reactivation of hemoglobin F production in patients with SCA. Meanwhile, an unprecedented number of new drugs aimed at both the treatment and prevention of end-organ damage are now in the pipeline, outcomes from potentially curative treatments such as allogeneic hematopoietic stem cell transplantation are improving, and great strides are being made in gene therapy, where methods employing both antisickling β-globin lentiviral vectors and gene editing are now entering clinical trials. Encouragingly, after a century of neglect, the profile of the vast majority of those with SCA in Africa and India is also finally improving.

Keywords: Africa; genetic modifiers; genetics; genomics; sickle cell anemia.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia, Sickle Cell / diagnosis
  • Anemia, Sickle Cell / genetics*
  • Anemia, Sickle Cell / physiopathology*
  • Anemia, Sickle Cell / therapy
  • Carrier Proteins / genetics
  • Genetic Therapy
  • Hemoglobins / metabolism
  • Humans
  • Nuclear Proteins / genetics
  • Phenotype*
  • Repressor Proteins
  • Treatment Outcome

Substances

  • BCL11A protein, human
  • Carrier Proteins
  • Hemoglobins
  • Nuclear Proteins
  • Repressor Proteins