MDS entities defined by genetic abnormalities in the ICC and WHO-HAEM5
| WHO-HAEM5 . | ICC . | Implications of genomic profiling . |
|---|---|---|
| MDS with low blasts and isolated 5q deletion | MDS with del(5q) | |
| BM blasts of <5% del(5q) alone or with 1 additional abnormality, except −7/del(7q) Any somatic mutation, except biallelic TP53 inactivation | BM blasts of <5% del(5q) alone or with 1 additional abnormality, except −7/del(7q) Any somatic mutation, except biallelic TP53 | Genomic profiling is fundamental to diagnosis. Patients with biallelic inactivation of TP53 have poor outcomes and are therefore classified as TP53-mutant MDS. |
| MDS with low blasts and SF3B1 mutation | MDS with mutated SF3B1 | |
| BM blasts of <5% Absence of del(5q), −7, or complex karyotype SF3B1 mutation, no biallelic TP53 | BM blasts of <5% Absence of del(5q), −7/del(7q), abn3q26.2, or complex karyotype SF3B1 mutation (VAF ≥10%), no biallelic TP53 inactivation, no RUNX1 mutation | Genomic profiling is fundamental to diagnosis (exclusion of biallelic inactivation of TP53) and important for prognosis. Patients with comutation patterns in other genes such as BCOR, BCORL1, NRAS, RUNX1, or STAG2 have worse clinical outcomes. |
| MDS with biallelic TP53 inactivation | MDS with mutated TP53 | |
| BM blasts of <20% Two or more TP53 mutations, or one mutation with evidence of TP53 copy number loss or cnLOH Usually complex karyotype | BM blasts of 0%-9% Biallelic TP53 inactivation∗ or TP53 mutation (VAF >10%) and complex karyotype often with loss of 17p† | This condition is associated with exceptionally poor clinical outcomes. The identification of a biallelic TP53 inactivation requires the implementation of ad hoc copy number and LOH analysis. |
| MDS/AML with mutated TP53 | ||
| BM blasts of 10%-19% Any somatic TP53 mutation (VAF >10%) |
| WHO-HAEM5 . | ICC . | Implications of genomic profiling . |
|---|---|---|
| MDS with low blasts and isolated 5q deletion | MDS with del(5q) | |
| BM blasts of <5% del(5q) alone or with 1 additional abnormality, except −7/del(7q) Any somatic mutation, except biallelic TP53 inactivation | BM blasts of <5% del(5q) alone or with 1 additional abnormality, except −7/del(7q) Any somatic mutation, except biallelic TP53 | Genomic profiling is fundamental to diagnosis. Patients with biallelic inactivation of TP53 have poor outcomes and are therefore classified as TP53-mutant MDS. |
| MDS with low blasts and SF3B1 mutation | MDS with mutated SF3B1 | |
| BM blasts of <5% Absence of del(5q), −7, or complex karyotype SF3B1 mutation, no biallelic TP53 | BM blasts of <5% Absence of del(5q), −7/del(7q), abn3q26.2, or complex karyotype SF3B1 mutation (VAF ≥10%), no biallelic TP53 inactivation, no RUNX1 mutation | Genomic profiling is fundamental to diagnosis (exclusion of biallelic inactivation of TP53) and important for prognosis. Patients with comutation patterns in other genes such as BCOR, BCORL1, NRAS, RUNX1, or STAG2 have worse clinical outcomes. |
| MDS with biallelic TP53 inactivation | MDS with mutated TP53 | |
| BM blasts of <20% Two or more TP53 mutations, or one mutation with evidence of TP53 copy number loss or cnLOH Usually complex karyotype | BM blasts of 0%-9% Biallelic TP53 inactivation∗ or TP53 mutation (VAF >10%) and complex karyotype often with loss of 17p† | This condition is associated with exceptionally poor clinical outcomes. The identification of a biallelic TP53 inactivation requires the implementation of ad hoc copy number and LOH analysis. |
| MDS/AML with mutated TP53 | ||
| BM blasts of 10%-19% Any somatic TP53 mutation (VAF >10%) |
BM, bone marrow; cnLOH, copy-neutral loss of heterozygosity; VAF, variant allele frequency.
Defined as 2 distinct TP53 mutations (each VAF of >10%) OR a single TP53 mutation with (1) 17p deletion on cytogenetics; (2) VAF of >50%; or (3) cnLOH at the 17p TP53 locus.
If TP53 locus LOH information is not available.