Studies of clonal evolution in patients who progressed to post-AA secondary MDS
| Reference (year) . | Study design (methodology) . | Median age, (range), y . | Patients, n . | Pre-MDS analysis . | MDS analysis . | Associations reported . | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Patients with malignancy-associated mutations, n (%) . | Reported mutations (n) . | Median allelic fraction (%) . | Patients with malignancy-associated mutations, n (%) . | Reported mutations (n) . | Karyotype at MDS transformation (n, %) . | |||||
| 9 (2014)* | Retrospective (Targeted NGS) | 54 (17-83) | 17 | 11 (65) | None (6), ASXL1 (7), DNMT3A (3), BCOR (1), ERBB2 (1), TET2 (1), U2AF1 (1) | 31 | N/A | N/A | Normal (10, 58), monosomy 7 (4, 24%), others in 1 patient each | AA patients with somatic mutations had a higher rate of MDS evolution. Patients with somatic mutations had shorter leukocyte telomere lengths. |
| 12 (2015)* | Retrospective (Sanger sequencing of ASXL1, TET2, RUNX1, TP53, K-RAS, N-RAS) | 21 (7-76) | 9 | 4 (44) | ASXL1 (3), TET2 (1) | N/A | N/A | N/A | Normal (5, 56), monosomy 7 (2, 22), others in 1 patient each | Patients with mutations in ASXL1 had a higher rate of MDS evolution. |
| 25 (2015) | Retrospective (WES, targeted NGS) of AA patients with monosomy 7 | 27 (18-68) | 13 | 2 (15) | Patient 1 (ASXL1, DNMT3A, SETBP1, DOT1L, STAT3). Patient 2 (DNMT3A, RUNX1). | ∼30 | 4 (31) | ASXL1 (4), DNMT3A (3), RUNX1 (3), SETBP1 (2), others | Monosomy 7 (13, 100) | Relatively low frequency of somatic mutations in patients with monosomy 7. Patients with monosomy 7 had shorter leukocyte telomere lengths. |
| 3 (2015)* | Retrospective (WES, targeted NGS) | 40.5 (2.5-88) | 16 | N/A | Various | N/A; clone size expanded over time | N/A | N/A | N/A | Patients with mutations in ASXL1, DNMT3A, RUNX1, JAK2, and JAK3 had worse overall and progression-free survival. Patients with mutations in PIGA, BCOR, BCORL1 had better overall and progression-free survival. |
| 7 (2017) | Retrospective (WES, targeted NGS) | 62 (18-75) | 23 | 4 of 8 (50) | RUNX1 (2), ASXL1 (1), U2AF1 (1), JAK2 (1), PHF6 (1), SETBP1 (1), TET2 (1) | 26 | 15 (65) | ASXL1, RUNX1, splicing factors, SETBP1, others | Monosomy 7 (17, 63) | Mutations in ASXL1, RUNX1, splicing factors, and CBL were associated with post-AA secondary MDS. |
| Reference (year) . | Study design (methodology) . | Median age, (range), y . | Patients, n . | Pre-MDS analysis . | MDS analysis . | Associations reported . | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Patients with malignancy-associated mutations, n (%) . | Reported mutations (n) . | Median allelic fraction (%) . | Patients with malignancy-associated mutations, n (%) . | Reported mutations (n) . | Karyotype at MDS transformation (n, %) . | |||||
| 9 (2014)* | Retrospective (Targeted NGS) | 54 (17-83) | 17 | 11 (65) | None (6), ASXL1 (7), DNMT3A (3), BCOR (1), ERBB2 (1), TET2 (1), U2AF1 (1) | 31 | N/A | N/A | Normal (10, 58), monosomy 7 (4, 24%), others in 1 patient each | AA patients with somatic mutations had a higher rate of MDS evolution. Patients with somatic mutations had shorter leukocyte telomere lengths. |
| 12 (2015)* | Retrospective (Sanger sequencing of ASXL1, TET2, RUNX1, TP53, K-RAS, N-RAS) | 21 (7-76) | 9 | 4 (44) | ASXL1 (3), TET2 (1) | N/A | N/A | N/A | Normal (5, 56), monosomy 7 (2, 22), others in 1 patient each | Patients with mutations in ASXL1 had a higher rate of MDS evolution. |
| 25 (2015) | Retrospective (WES, targeted NGS) of AA patients with monosomy 7 | 27 (18-68) | 13 | 2 (15) | Patient 1 (ASXL1, DNMT3A, SETBP1, DOT1L, STAT3). Patient 2 (DNMT3A, RUNX1). | ∼30 | 4 (31) | ASXL1 (4), DNMT3A (3), RUNX1 (3), SETBP1 (2), others | Monosomy 7 (13, 100) | Relatively low frequency of somatic mutations in patients with monosomy 7. Patients with monosomy 7 had shorter leukocyte telomere lengths. |
| 3 (2015)* | Retrospective (WES, targeted NGS) | 40.5 (2.5-88) | 16 | N/A | Various | N/A; clone size expanded over time | N/A | N/A | N/A | Patients with mutations in ASXL1, DNMT3A, RUNX1, JAK2, and JAK3 had worse overall and progression-free survival. Patients with mutations in PIGA, BCOR, BCORL1 had better overall and progression-free survival. |
| 7 (2017) | Retrospective (WES, targeted NGS) | 62 (18-75) | 23 | 4 of 8 (50) | RUNX1 (2), ASXL1 (1), U2AF1 (1), JAK2 (1), PHF6 (1), SETBP1 (1), TET2 (1) | 26 | 15 (65) | ASXL1, RUNX1, splicing factors, SETBP1, others | Monosomy 7 (17, 63) | Mutations in ASXL1, RUNX1, splicing factors, and CBL were associated with post-AA secondary MDS. |
N/A, not available.
Data shown correspond to the subset of patients who progressed to post-AA secondary MDS.