Table 2.
CH in AA and the general population
| Aplastic anemia | Normal individuals | MDS | |
|---|---|---|---|
| Mutations | High (>50%) | Low (∼2%) | Very high (∼90%)* |
| Correlation to age | Positive | Positive | Positive |
| Mutated <40 y, % | 20-40 | <1 | |
| Mutated >70 y, % | 52 | >10 | |
| Signature | Age-related C to T transitions | Age-related C to T transitions | Age-related C to T transitions |
| Commonly mutated genes | BCOR/BCORL1, PIGA, DNMT3A, ASXL1 | DNMT3A, TET2, ASXL1, JAK2, TP53, SF3B1 | TET2, SF3B1, ASXL1, SRSF2, DNMT3A, RUNX1, TP53 |
| Variant allele frequency | Low (generally <10%) | Low (generally <10%) | High (>30%) |
| Copy number variations, % | ∼20 | <2 | ∼50 |
| Cytogenetics SNP array karyotyping | UPD in 6p | del(20q) | −5/del(5q) |
| −7/del(7q) | del(13q) | −7/del(7q) | |
| +6 | del(11q) | +8 | |
| +8 | 17pLOH | 17pLOH | |
| +15 | UPD in 4q, 9p, 11q, 14q | del(20q) | |
| del(13q) | UPDs in 4q, 11q, 13q, 14q | ||
| Impact of CH on progression to MDS/AML | ∼3% for BCOR, BCORL1, and PIGA mutations | Relative risk: ∼10× to ∼35× | |
| ∼40% for DNMT3A, ASXL1, RUNX1, TP53, and CSMD2 mutations |
*
By abnormal cytogenetic and somatic mutations.