Acquired DNA mutations associated with in vivo hydroxyurea exposure

The long-term safety of hydroxyurea in blood disorders remains unclear. While short-term effects are well-documented, its mutagenic potential is not fully understood. Some studies link hydroxyurea to leukemia in myeloproliferative patients. This uncertainty limits its use in chronic conditions like sickle cell disease. Researchers have not yet resolved how hydroxyurea affects DNA over time. The lack of data on mutation rates in treated patients creates a knowledge gap. This study aimed to address this by measuring DNA changes in blood cells. Understanding these changes could guide safer treatment protocols.

This research aimed to assess the mutagenic effects of hydroxyurea in blood cells. The focus was on acquired DNA mutations in patients with myeloproliferative disorders and sickle cell disease. The team used two assays to detect somatic mutations in peripheral blood cells. They compared mutation rates across different exposure durations. The goal was to determine if hydroxyurea increases mutation risk. The study included patients with varying treatment histories. Researchers wanted to clarify the long-term safety of hydroxyurea. Their findings could influence clinical use and monitoring strategies.

The study used two assays to detect DNA mutations in blood cells. The HPRT assay measured hprt gene mutations. The VDJ assay identified T-cell receptor recombination events. Blood samples were collected from patients and controls. Participants included those with myeloproliferative disorders and sickle cell disease. Mutation counts were compared based on hydroxyurea exposure. Statistical analysis evaluated differences between groups. The team focused on peripheral blood mononuclear cells. They analyzed mutation rates in adults and children separately.

Patients with myeloproliferative disorders showed no increase in DNA mutations. Mutation rates were similar between long-term and short-term hydroxyurea users. Sickle cell adults had consistent mutation levels regardless of exposure. Children with sickle cell and 30 months of hydroxyurea had higher VDJ mutations. The average was 1.82 events per microgram of DNA in long-term users. Short-term users had 1.58 events, and controls had 1.06 events. The difference reached statistical significance at P = 0.04. These results suggest limited mutagenic effects of hydroxyurea in most groups.

The study suggests that hydroxyurea has low mutagenic potential in most patient groups. Mutation rates in myeloproliferative patients were not higher with long-term use. Sickle cell adults showed no exposure-related differences in DNA changes. Children with longer hydroxyurea exposure had more VDJ mutations. This increase was statistically significant but not necessarily linked to leukemia. The authors propose monitoring young sickle cell patients for mutation trends. They recommend serial assessments to detect any increases. These findings support continued use of hydroxyurea with careful monitoring.