Sensitivity to cisplatin-induced mutations and elevated chromosomal aberrations in lymphocytes from sickle cell disease patients

Abstract

Sickle cell disease (SCD) is an inherited disorder caused by a single nucleotide substitution in the beta-globin gene. The clinical heterogeneity observed in SCD patients has been attributed to environmental and genetic factors. The patients are subjected to increased oxidative stress, particularly during vaso-occlusive crises and acute chest pain. Another possible cause of oxidative stress in SCD is the high concentration of iron in the patients' plasma. The increase in oxidative stress could be a relevant risk factor for mutagenesis and carcinogenesis. Studies on the frequency of basal chromosomal aberrations in cultured lymphocytes from SCD patients have not been reported so far. In order to contribute to the understanding of the role of the different biomarkers and their relationship with the extremely variable clinical manifestation of SCD, we investigated the frequency of chromosome damage in peripheral lymphocytes from sickle cells patients and healthy controls. We found an increased frequency of chromosome damage and percentage of aberrant metaphases in these patients when compared with control subjects, even at basal values (p<0.05). In the cytogenetic sensitivity assay, the results showed that these patients presented a marked decrease in the mitotic index values compared with healthy controls. Cisplatin-induced chromosomal damage in lymphocytes from these patients was significantly higher than the frequency measured in healthy controls. The results obtained in the present study showed that more investigations are needed in order to elucidate the susceptibility to genomic instability of SCD patients.

Sickle cell disease and acute leukemia: one case report and an extensive review

“…The pro-tumorigenic role of inflammasomes is associated with promoting cell proliferation, inhibition of apoptosis, and an immunosuppressive effect on the immune cells. Constant hematopoietic hyperplasia, stimulated by a hemolysis-induced cytokine storm, may increase the risk of somatic mutations, resulting in transformation of myeloid precursors [ 71 ]. Other factors associated with the increased risk include increased risk of infections, and increased bone marrow turnover, which form the pathophysiologic mechanisms of the clinical manifestations of SCD [ 5 , 72 ].…”

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

“…In this setting, inflammasomes behave as pro-tumorigenic agents associated with the promotion of cell proliferation, inhibition of apoptosis, and an immunosuppressive effect on the immune cells [ 9 ]. Constant hematopoietic hyperplasia, stimulated by a hemolysis-induced cytokine storm, may also increase the risk of somatic mutations, resulting in a potential transformation of myeloid precursors [ 10 ].…”