Precision diagnostic criteria for MDS-del(5q)
| Disease-defining criteria (current diagnostic criteria according to ICC 20226 and WHO 20227 ) |
| Cytopenias: ≥1 (typically, anemia with normal to low white blood cell count and normal to elevated platelet count) |
| Dysplasia: ≥1 lineage (typically, dysmegakaryopoiesis consisting of megakaryocytes with hypolobulated nuclei) |
| Chromosomal 5q deletion, with up to 1 additional chromosomal aberration, except monosomy 7 or del(7q) |
| Absence of TP53 multihit lesions∗ |
| Blast count as a disease stage indicator. Although both ICC 20226 and WHO 20227 require a blast count of <5%, a more logical classification would be: |
| MDS-del(5q) with low blasts (blast count of less than 5%, indicating an initial or chronic phase of the disease) |
| MDS-del(5q) with increased blasts (blast count ranging from 5% to 19%, indicating an advanced phase of the disease) |
| Molecular qualifier (co-occurring somatic mutation) and its clinical implications |
| Somatic DTA mutation† |
| Co-occurring DTA mutations usually indicate age-related clonal hematopoiesis and have limited clinical significance |
| Somatic mutation in SF3B1 |
| A concomitant SF3B1 mutation, which is typically associated with the presence of ring sideroblasts, has a significant impact on clinical outcomes, with a substantial reduction in overall survival and an increased risk of leukemic transformation |
| Monoallelic TP53 mutation |
| No major impact on clinical outcomes per se. Potential risk of transition from monoallelic mutation to TP53 multihit state under lenalidomide treatment, with progression to a t-MN. Patients with high mutation VAF may have small, difficult-to-detect TP53 biallelic clones before treatment. |
| Somatic mutation in RUNX1 |
| A co-occurring mutation in RUNX1 markedly affects clinical outcomes, with poor response to lenalidomide, poor overall survival, and a very high risk of leukemic transformation |
| Somatic mutation in CSNK1A1 |
| A concomitant mutation in the nondeleted CSNK1A1 allele is associated with poor response to lenalidomide and an elevated risk of progression to a t-MN |
| Disease-defining criteria (current diagnostic criteria according to ICC 20226 and WHO 20227 ) |
| Cytopenias: ≥1 (typically, anemia with normal to low white blood cell count and normal to elevated platelet count) |
| Dysplasia: ≥1 lineage (typically, dysmegakaryopoiesis consisting of megakaryocytes with hypolobulated nuclei) |
| Chromosomal 5q deletion, with up to 1 additional chromosomal aberration, except monosomy 7 or del(7q) |
| Absence of TP53 multihit lesions∗ |
| Blast count as a disease stage indicator. Although both ICC 20226 and WHO 20227 require a blast count of <5%, a more logical classification would be: |
| MDS-del(5q) with low blasts (blast count of less than 5%, indicating an initial or chronic phase of the disease) |
| MDS-del(5q) with increased blasts (blast count ranging from 5% to 19%, indicating an advanced phase of the disease) |
| Molecular qualifier (co-occurring somatic mutation) and its clinical implications |
| Somatic DTA mutation† |
| Co-occurring DTA mutations usually indicate age-related clonal hematopoiesis and have limited clinical significance |
| Somatic mutation in SF3B1 |
| A concomitant SF3B1 mutation, which is typically associated with the presence of ring sideroblasts, has a significant impact on clinical outcomes, with a substantial reduction in overall survival and an increased risk of leukemic transformation |
| Monoallelic TP53 mutation |
| No major impact on clinical outcomes per se. Potential risk of transition from monoallelic mutation to TP53 multihit state under lenalidomide treatment, with progression to a t-MN. Patients with high mutation VAF may have small, difficult-to-detect TP53 biallelic clones before treatment. |
| Somatic mutation in RUNX1 |
| A co-occurring mutation in RUNX1 markedly affects clinical outcomes, with poor response to lenalidomide, poor overall survival, and a very high risk of leukemic transformation |
| Somatic mutation in CSNK1A1 |
| A concomitant mutation in the nondeleted CSNK1A1 allele is associated with poor response to lenalidomide and an elevated risk of progression to a t-MN |
Defined as the presence of either 2 TP53 mutations (in trans) or 1 TP53 mutation with loss of the second TP53 allele, due to a deletion of the TP53 locus on chromosome 17p detected by karyotype or FISH, or copy-neutral loss of heterozygosity. Multihit TP53 state can also be inferred by a TP53 VAF >50%.
DTA: DNMT3A, TET2, and AXSL1.