Table 1 Areas of discrepancy between the 5th edition of the World Health Organization (WHO-5) and the International Consensus Classifications (ICC).
No. | Area of discrepancy | WHO-5 (MDS with biallelic TP53 inactivation) | ICC (Myeloid neoplasms with mutated TP53) | Evidence presented | Conclusion |
|---|---|---|---|---|---|
1 | Acute myeloid leukemia (AML) | No separate category, most cases would be classified as AML-MR | Separate category (BM/PB blasts ≥20%), includes AEL | Survival of TP53mut AML is significantly poorer compared to TP53wt AML-MR (4.7 vs. 18.3 months; P < 0.0001). | TP53mut AML should be included in TP53mut MN |
2 | Interaction of blast percentage category with allelic status | Requires demonstration of biallelic loss for 0–19% blasts | Requires demonstration of biallelic loss for 0–9% blasts | Survival of monoallelic TP53mut MDS with 10–19% blasts is comparable to biallelic loss. | Monoallelic TP53mut MDS with 10–19% blasts should be considered TP53mut MN |
3 | Confirmation of 17p13.1 deletion detected on karyotype by CNV analysis | Requires confirmation of loss of the TP53 locus detected on the karyotype with an additional CNA method | Does not require confirmation of 17p13.1 deletion | Cases with single TP53mut (VAF < 50%) with 17p13.1 deletion on karyotype: CNV analysis verified the LOH across the TP53 locus in 94% of evaluable cases. Cases with single TP53mut (VAF < 50%) without 17p13.1 deletion on karyotype: • CNV analysis identified LOH/cnLOH in 26.9% of evaluable cases. • Importantly, all cases with LOH/cnLOH across the TP53 locus on CNV analysis had CK. • Conversely, no LOH/cnLOH was observed in cases with or without CK | In a single TP53mut with VAF < 50%, confirmation of 17p deletion with an additional CNV is not necessary |
4 | CK as a multi-hit equivalent | CK is not considered a multi-hit equivalent | CK is considered a multi-hit equivalent | Survival of single TP53mut VAF < 50% with CK was comparable to those with 17p deletion on karyotype (10.4 vs. 11.0 months; P = 0.39) and poorer than monoallelic TP53mut without 17p loss or CK (33.4 months; P < 0.0001) | In single TP53mut with VAF < 50%, CK should be considered multi-hit equivalent |
5 | VAF threshold | None | VAF ≥ 10% | Survival of TP53mut ‘multi-hit’ VAF 2 to <10% was shorter compared to that of ‘single-hit’ TP53mut VAF < 10%, but comparable to VAF ≥ 10% (14.1 vs. 48.8 vs. 7.8 months, P < 0.0001). | ‘Multi-hit’ TP53mut with VAF 2 to <10% should be included in TP53mut MN |
