Table 3. Monitoring TP53 mutations over time.
| Sample ID | Retrospective (R) /prospective (P) analysis | First available sample: time from dg (y) | Study enrollment: time from dg (years) | Last available sample: time from dg (years) | Total follow-up (years) | MPN therapy before study enrollment | Therapy after study enrollment | Mutation ⩾0.1% in dg sample | The development of most abundant mutation (%) a | Mutation development during follow-up |
|---|---|---|---|---|---|---|---|---|---|---|
| 186A | R | 0.0 | 15.0 | 15.0 | 15.0 | IFN | HUb | yes | 0.4-8.3-NA | Increase |
| MP15 | P/R | 0.2 | 7.0 | 11.9 | 11.5 | HU, IFN | IFN | no | 0-0.8-2.1-2.6-3.8-4.4-10.7-11.3-11.2(W)13.8(G) | |
| MP10 | P/R | 0.0 | 6.4 | 9.8 | 9.8 | HU | HU | no | 0-10.1-85.5 | |
| JAK1716 | P/R | 6.0 | 9.3 | 16.2 | 10.2 | IFN | IFN→HU | NA | 0-0.1-0.1-0.2-0.7-2.2-2-2.2 | |
| MP326 | P/R | 0.0 | 6.7 | 9.1 | 9.1 | HU | HU | no | 0-0.6-0.5-0.5 | |
| MP96 | P/R | 0.0 | 5.4 | 8.8 | 8.8 | HU | HU | no | 0-0.5-0.6 | |
| MP168 | P/R | 2.4 | 7.1 | 10.5 | 8.1 | HU | HU | NA | 0.1-1-0.5-0.6 | |
| MP319 | P/R | 0.0 | 5.2 | 7.5 | 7.5 | HU, ANA | HU, ANA | yes | 0.1-0.4-0.4-0.8 | |
| MP369 | P | 0.0 | 0.0 | 7.0 | 7.0 | nonec | HU | NA | NA-0.13-1.4 | |
| 65A | P | 13.2 | 13.2 | 19.6 | 6.5 | IFN, ANA | IFN, ANA | NA | NA-1.7-5.4 | |
| MP327 | P/R | 4.9 | 10.4 | 11.2 | 6.3 | HU | HU | NA | 0-0.1-0.5-0.5 | |
| JAK22 | P | 0.0 | 0.0 | 5.0 | 5.0 | nonec | HU | yes | NA-2.0-46.1 | |
| MP273 | P | 9.3 | 9.3 | 12.0 | 2.8 | HU | HU | NA | NA-0.3/0-0.3/1.7 | |
| MP317 | P | 5.5 | 5.5 | 6.0 | 0.5 | HU | HU | NA | NA-0.8-1.9 | |
| MP289 | P/R | 15.2 | 22.1 | 24.6 | 9.3 | HU, IFN | none | NA | 0.2/1.4-3.3/0.7-4.4/0.4-6.3/0.6-3.5/0.4d | Increase/decrease |
| MP68 | P/R | 0.0 | 4.8 | 8.3 | 8.3 | HU, ANA | HU→none | no | 0-6.9-8.8-10.7-11.7-16.9-9.6-2.7 | |
| MP315 | P/R | 4.6 | 9.1 | 11.5 | 6.9 | IFN | IFN | NA | 0.2-0.8-0.4-0.2 | |
| MP230 | P | 8.0 | 8.0 | 9.2 | 1.2 | HU | HU | NA | NA-0.5-2.3-1.3 | |
| MP189 | P/R | 6.9 | 11.5 | 14.6 | 7.7 | ANA | HU, ANA | NA | 3.9-2.8-2.5 | Stable |
| MP155 | P/R | 5.7 | 10.2 | 13.0 | 7.3 | ANA | ANA | NA | 0.4-0.2-0.2 | |
| MP229 | P | 9.4 | 9.4 | 12.4 | 3.0 | HU | HU, ANA | NA | NA-1-0.5-0.6 | |
| MP302 | P | 19.3 | 19.3 | 21.7 | 2.4 | busulfan→HU | HU | NA | NA-0.4-0.4-0.7 | |
| MP329 | P | 13.5 | 13.5 | 15.7 | 2.2 | HU | HU, ANA | NA | NA-2.6-1.9-3.1/3.0 | |
| MP324 | P | 21.2 | 21.2 | 22.0 | 0.7 | HU | HU | NA | NA-0.3-0.4 | |
| 221A | P/R | 0.0 | 15.0 | 24.6 | 24.6 | IFN | IFN | yes | 10.2/ND-2.2/0.6-0.7/2.0d | Decrease |
| MP2 | P/R | 12.1 | 16.3 | 21.7 | 9.6 | HU, IFN, ANA | HU, ANA | NA | 11.5-10.6-11.6-2.9-2.2-1.9-2.1 | |
| MP63 | P/R | 1.5 | 6.6 | 10.0 | 8.5 | HU | HU | NA | 0-0.2/0.1-0.1/0.2-0/0d | |
| MP160 | P/R | 1.2 | 5.1 | 7.1 | 5.8 | HU | HU | NA | 0.5-0.2-0 | |
| MP307 | P | 8.6 | 8.6 | 10.2 | 1.6 | HU | HU | NA | 0.2-0 | |
| MP314 | P/R | 14.8 | 19.4 | 21.9 | 7.1 | busulfan→HU | HU | NA | 3.3/0.2-1.3/0.4-0.6/0.9-0.2/0.2d | |
| MP345 | P/R | 0.0 | 4.2 | 6.3 | 6.3 | HU | HU | yes | 0.1-1.1-0.9-0.5-0.6 |
Abbreviations: G, granulocytes; NA, not available; W, leukocytes.
Mutations with highest VAF are shown. "Study enrollment" describes the sampling from which the mutation was identified. For over-time monitoring and validation of previously identified mutation, cut-off 0.1% was applied (minimal coverage per base ⩾10000). VAF bellow 0.1% considered as a background (0%). Development was cathegorised as follows: increase—VAF twofold increase between first and last sample or no mutation at diagnosis; decrease—VAF decrease in VAF to half between first and last sample or no mutation at last sampling; increase/decrease—increase followed by decrease; stable—other. y, years; NA, not available; G, granulocytes; W, leukocytes.
Result from study enrollment is highlighted.
Samples not available.
Mutation identified at diagnosis.
Two mutations with the highest VAFs in distinct samplings.