Quantitation of acquired DNA mutations in association with in vivo hydroxyurea exposure
| Patient population . | No.patients . | Mean age (years) . | Median HU exposure . | HPRT cloning efficiency (%) . | HPRT mutational frequency (×10−6) . | VDJ events (per μg DNA) . |
|---|---|---|---|---|---|---|
| Adults with MPD | 27 | |||||
| Low HU exposure | 15 | 57 ± 17 | 0 months | 12.8 ± 8.9 | 37.3 ± 37.6 | 1.06 ± 0.73 |
| Prolonged HU exposure | 12 | 62 ± 16 | 11 years | 12.2 ± 8.4 | 41.1 ± 29.3 | 0.64 ± 0.29 |
| Adults with SCD | 30 | |||||
| No HU exposure | 15 | 27 ± 12 | 0 months | 15.1 ± 12.3 | 19.1 ± 19.1 | 1.07 ± 0.38 |
| Short HU exposure | 15 | 29 ± 9 | 24 months | 12.4 ± 8.2 | 16.7 ± 10.9 | 1.14 ± 0.38 |
| Children with SCD | 38 | |||||
| No HU exposure | 21 | 11 ± 3 | 0 months | 14.9 ± 8.3 | 11.5 ± 18.7 | 1.06 ± 0.45 |
| With HU exposure | 17 | |||||
| After short HU exposure | 11 ± 3 | 7 months | 13.2 ± 6.1 | 11.2 ± 6.7 | 1.58 ± 0.87 | |
| After longer HU exposure | 13 ± 3 | 30 months | 20.9 ± 10.2 | 9.2 ± 7.8 | 1.82 ± 1.20 | |
| Normal controls | 32 | 43 ± 15 | 0 months | 16.0 ± 8.7 | 25.8 ± 24.8 | 1.04 ± 0.38 |
| Ataxia telangiectasia | 1 | 9 | 0 months | 2.3 | 240.7 | 12.99 |
| Patient population . | No.patients . | Mean age (years) . | Median HU exposure . | HPRT cloning efficiency (%) . | HPRT mutational frequency (×10−6) . | VDJ events (per μg DNA) . |
|---|---|---|---|---|---|---|
| Adults with MPD | 27 | |||||
| Low HU exposure | 15 | 57 ± 17 | 0 months | 12.8 ± 8.9 | 37.3 ± 37.6 | 1.06 ± 0.73 |
| Prolonged HU exposure | 12 | 62 ± 16 | 11 years | 12.2 ± 8.4 | 41.1 ± 29.3 | 0.64 ± 0.29 |
| Adults with SCD | 30 | |||||
| No HU exposure | 15 | 27 ± 12 | 0 months | 15.1 ± 12.3 | 19.1 ± 19.1 | 1.07 ± 0.38 |
| Short HU exposure | 15 | 29 ± 9 | 24 months | 12.4 ± 8.2 | 16.7 ± 10.9 | 1.14 ± 0.38 |
| Children with SCD | 38 | |||||
| No HU exposure | 21 | 11 ± 3 | 0 months | 14.9 ± 8.3 | 11.5 ± 18.7 | 1.06 ± 0.45 |
| With HU exposure | 17 | |||||
| After short HU exposure | 11 ± 3 | 7 months | 13.2 ± 6.1 | 11.2 ± 6.7 | 1.58 ± 0.87 | |
| After longer HU exposure | 13 ± 3 | 30 months | 20.9 ± 10.2 | 9.2 ± 7.8 | 1.82 ± 1.20 | |
| Normal controls | 32 | 43 ± 15 | 0 months | 16.0 ± 8.7 | 25.8 ± 24.8 | 1.04 ± 0.38 |
| Ataxia telangiectasia | 1 | 9 | 0 months | 2.3 | 240.7 | 12.99 |
HU indicates hydroxyurea; MPD, myeloproliferative disorder; SCD, sickle cell disease; VDJ events, T-cell receptor V-J interlocus recombination events.
Note: Patient and control PBMCs were tested for acquired DNA mutations in both the HPRT and VDJ assays. The adults with MPD or SCD had no significant differences in hprt cloning efficiency, mutational frequency, or VDJ recombination events, according to HU exposure. Children with SCD and HU exposure had a trend for more VDJ events compared with those with no HU exposure, P = .04 by ANOVA (with no adjustment for multiple comparisons). The child with ataxia telangiectasia had increased numbers of acquired DNA mutations in both assays.36