Sickle cell disease in the era of precision medicine: looking to the future

ABSTRACT

Introduction: Sickle cell anemia is a Mendelian disease that is noted for the heterogeneity of its clinical expression. Because of this, providing an accurate prognosis has been a longtime quest.

Areas covered: Reviewed are the benefits and shortcomings of testing for the major modulators of the severity of the disease, like fetal hemoglobin and α thalassemia, along with studies that have attempted to link genetic variation with sub-phenotypes of disease in a predictive fashion. Induced pluripotent stem cells driven to differentiate into erythroid precursor cells provide another area for potential patient-specific drug testing.

Expert opinion: Fetal hemoglobin is the strongest modulator of sickle cell anemia but simply measuring its blood levels is an insufficient means of forecasting an individual’s prognosis. A more precise method would be to know the distribution of fetal hemoglobin levels across the population of red cells, an assay not yet available. Prognostic measures have been developed using genetic and other signatures, but their predictive value is suboptimal. Widely applicable assays must be developed to allow a tailored approach to using several new treatments that are likely to be available in the near future.

KEYWORDS:

• HbF
• GWAS
• iPSCs

Article highlights

• New disease-modifying therapeutic options for sickle cell anemia are likely to become available in the next 1 to 5 years.

• These options will include both drug and cell-based therapeutics.

• Risk stratification based on genetic and other biomarkers would be useful for tailoring treatment to the patients.

• Although our understanding of the genetic basis of the clinical heterogeneity of sickle cell anemia has improved, few biomarkers, genetic or otherwise, are sufficiently precise for individualized prognosis or treatment decisions.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported in part by the NIH, NHLBI under Grants U01 HL107443; R01 HL 87681; R01 HL 068970; RC2 HL101212.