Is There any Relationship Between the Repeated Complications of Sickle Cell Disease and the Potential Development of Acute Leukemia?

Abstract

Sickle cell disease (SCD) is a severe monogenic hereditary hemoglobinopathy that is characterized by repeated clinical and biological manifestations able to generate stress erythopoiesis. A clonal hematopoiesis involving mainly variants of TP53, DNMT3A, ASXL1, and/or TET2 may be more prevalent in patients with SCD, suggesting that mutations in these genes may lead to an increased risk of leukemia. An increased prevalence of leukemia in patients with SCD has been confirmed by an increasing number of acute myeloid leukemia cases with myelodysplastic features reported in this patient population even in the absence of disease-modifying treatments. This leads to the hypothesis of a mechanism involving multifactorial causes through the pathophysiologic manifestations of SCD, in which cells are undergoing constant hematopoietic hyperplasia, inducing genomic damage and somatic mutations.

Keywords: Acute leukemia; Clonal hematopoiesis; Mutations; Sickle cell disease.

Fig. 1

Repetitive chronic clinical and biological manifestations may lead to patients with SCD developing clonal hematopoiesis over time that (following further hits) may or may not evolve to clonal expansion and potentially to malignant disease. AML Acute myeloid leukemia, BM bone marrow, CCUS clonal cytopenia of undetermined significance, HSC hematopoietic stem cell, ICUS idiopathic cytopenia of undetermined significance, IDUS idiopathic dysplasia of undetermined significance, MDS myelodysplastic syndrome, SCD sickle cell disease