Table 1. Twenty cases with SF3B1 mutations examined serially.
Patient number | Prior Tx | SF3B1 mutation | IGHV status | ZAP-70 status | FISH abnormality | Initial ratio (%)a | Increase over time (%) | First to last SC (months) | Increase/month (%) | P-value |
---|---|---|---|---|---|---|---|---|---|---|
1 | Yes | K700E | UM | Pos | del(17p) | 30.1 | 45.5 | 7.9 | 5.8 | 0.0091 |
2 | No | E622D | MU | Neg | del(13q) | 37.0 | 63.1 | 12.9 | 4.9 | 0.0095 |
3 | No | K700E | MU | Neg | None | 16.3 | 161.2 | 40.2 | 4.0 | 0.0022 |
4 | No | G740E | UM | Pos | None | 23.9 | 62.1 | 23.6 | 2.6 | 0.0096 |
5 | Yes | G740E | UM | Pos | None | 39.0 | 23.1 | 9.8 | 2.4 | 0.0111 |
6 | Yes | R625C | UM | Pos | None | 30.8 | 34.2 | 16.6 | 2.1 | 0.0464 |
7 | Yes | K700E | MU | Pos | None | 30.5 | 32.3 | 27.3 | 1.2 | 0.0017 |
8 | No | K700E | UM | Pos | del(13q) | 36.1 | 27.7 | 24.1 | 1.1 | 0.1472 |
9 | No | K700E | UM | Pos | None | 33.0 | 17.8 | 16.1 | 1.1 | 0.2104 |
10 | No | K666E | UM | Neg | None | 45.4 | 6.8 | 6.3 | 1.1 | 0.0726 |
11 | No | K666E | UM | Pos | del(11q) | 46.9 | 7.3 | 11.1 | 0.7 | 0.1641 |
12 | No | K666N | UM | Neg | trisomy 12 | 49.9 | 10.4 | 23.8 | 0.4 | 0.1643 |
13 | Yes | K666Q | UM | Pos | del(11q) | 20.9 | 3.0 | 11.0 | 0.3 | 0.0750 |
14 | No | E622D | UM | Pos | del(11q) | 61.6 | 6.8 | 36.1 | 0.2 | 0.1413 |
15 | Yes | K700E | MU | Neg | del(13q) | 46.3 | 1.2 | 10.3 | 0.1 | 0.7482 |
16 | Yes | K700E | UM | Pos | None | 45.9 | −0.3 | 35.7 | 0.0 | 0.7762 |
17 | Yes | K700E | UM | Pos | del(11q) | 48.7 | −2.3 | 61.5 | 0.0 | 0.7643 |
18 | No | N626Y | UM | Pos | del(13q) | 52.5 | −1.9 | 23.8 | −0.1 | 0.4690 |
19 | Yes | K741T | MU | Neg | del(13q) | 63.7 | −4.7 | 52.0 | −0.1 | 0.1531 |
20 | Yes | K700E | MU | Neg | del(13q) | 49.2 | −11.7 | 26.7 | −0.4 | 0.2838 |
Abbreviations: FISH, fluorescence in situ hybridization; IGHV, immunoglobulin heavy chain variable; MU, mutated; neg, negative; pos, positive; SC, sample collection ; UM, unmutated.
The column marked ‘Prior Tx' indicates whether the patient did (yes) or did not (no) have prior therapy for CLL. The column marked ‘SF3B1 mutation' provides the site (middle number) and amino-acid residue of the wild-type and mutant allele, using standard single-letter amino-acid nomenclature. The column marked ‘IGHV status' provides the mutation status for the expressed IGHV gene, which was considered UM when it had ⩾98% identity with the germ-line IGHV or MU when it had <98% identity. The column marked ‘ZAP-70 status' indicates whether the CLL sample was pos or neg for ZAP-70, as assessed via flow cytometry. The column marked ‘FISH abnormality' provides the abnormal FISH finding (if any) for the initial sample. The column marked ‘Initial ratio (%)' provides the proportionate representation of the SF3B1-mutant allele in this initial sample. The column labeled ‘increase over time (%)' provides the percent increase in the proportionate representation of the mutant SF3B1 allele, which was calculated with the formula 100 × [(mutant allele ratio of the last SC - mutant allele ratio of the first SC)/mutant allele ratio of the first SC]. The column marked ‘First to last SC (months)' provides the number of months between the last SC and first SC. The column labeled ‘Increase/months (%)' was calculated by dividing the value in the column marked ‘Increase over time' by the value in the column labeled ‘First to last SC'. The P-values were calculated using the Student's t-test when two time points were available or using the one-way analysis of variance when data from three or more time points from the same case were available.
Initial proportionate representation of the SF3B1-mutant allele according to the formula 100 × (M peak intensity/(M peak intensity+WT peak intensity)).