Genetic features of NPM1 mutations
| Heterozygous mutations detected in about one third of adult AML (50-60% of AML with normal cytogenetic). Less frequent in children (∼7%). |
| Mostly restricted to exon 12 (<1% other exons). Mutation A (duplication TCTG) is the most common mutation (75-80% of cases), followed by mutations B and D (∼5% each). |
| Probably arising from replication errors primed by illegitimate terminal deoxynucleotidyl transferase activity. |
| Found in the whole leukemic population (as proven by IHC) and stable over time (being detected at relapse*). |
| Not detected in individuals with clonal hematopoiesis. Driver mutations acting as “gatekeepers” for AML, mostly de novo. |
| Frequently co-occur with mutations of FLT3, DNMT3A, and IDH1/2 genes. Prognosis may vary according to the associated mutations. |
| Mutually exclusive with AML entities defined by recurrent genetic abnormalities in the 2017 WHO classification of hematopoietic tumors. |
| Close association with normal karyotype (∼85% of cases). About 15% of cases carry chromosome aberrations, especially +8, del(9q), +4. |
| Associated with distinct gene expression profile characterized by upregulation of HOX genes (HOXA, HOXB) and low expression of CD34 and CD133. |
| Close association with distinct microRNA and long noncoding RNA profiles. |
| Heterozygous mutations detected in about one third of adult AML (50-60% of AML with normal cytogenetic). Less frequent in children (∼7%). |
| Mostly restricted to exon 12 (<1% other exons). Mutation A (duplication TCTG) is the most common mutation (75-80% of cases), followed by mutations B and D (∼5% each). |
| Probably arising from replication errors primed by illegitimate terminal deoxynucleotidyl transferase activity. |
| Found in the whole leukemic population (as proven by IHC) and stable over time (being detected at relapse*). |
| Not detected in individuals with clonal hematopoiesis. Driver mutations acting as “gatekeepers” for AML, mostly de novo. |
| Frequently co-occur with mutations of FLT3, DNMT3A, and IDH1/2 genes. Prognosis may vary according to the associated mutations. |
| Mutually exclusive with AML entities defined by recurrent genetic abnormalities in the 2017 WHO classification of hematopoietic tumors. |
| Close association with normal karyotype (∼85% of cases). About 15% of cases carry chromosome aberrations, especially +8, del(9q), +4. |
| Associated with distinct gene expression profile characterized by upregulation of HOX genes (HOXA, HOXB) and low expression of CD34 and CD133. |
| Close association with distinct microRNA and long noncoding RNA profiles. |
With the exception of rare cases of second AML occurring in the context of clonal hematopoiesis (see text).