Table 1.
Promising molecules for therapeutic targeting of mutant NPM1 in AML.
| Molecules | Target cells | Consequences in cellular processes | Study |
|---|---|---|---|
| ATRA/ATO | OCI-AML3 and IMS-M2 (NPM1 mutated cell lines) | Proteasome-dependent degradation of NPM1c protein | Martelli109 |
| AML patient primary cells with NPM1 mutation | Oxidative stress induction/cell apoptosis | ||
| EAPB0503 | OCI-AML3 | Proteasome-mediated degradation of NPM1c protein | Nabbouh110 |
| OCI-AML3 xenograft mice | Restore wt-NPM1 nucleolar localization/growth arrest/apoptosis | ||
| NSC348884 | OCI-AML3 | Interference with the oligomerization of NPM1 | Balusu111 |
| AML patient primary cells with NPM1 mutation | Cell apoptosis/sensitize NPM1c+ AML cells to ATRA | ||
| MI-2-2 | OCI-AML3 | Inhibition of menin-MLL1 and DOT1L | Kuhn112 |
| EPZ4777 | AML patient primary cells with NPM1 mutation | Suppression of HOX and FLT3 expression | |
| MI-503 | OCI-AML3 xenograft mice | Cell differentiation/inhibition NPM1mut leukemia initiation |
AML, acute myeloid leukemia; ATO, arsenic trioxide; ATRA, all-trans retinoic acid; EAPB0503, 1-(3-methoxyphenyl)-N-methylimidazoquinoxalin-4-amine; FLT3, fms-related tyrosine kinase 3; HOX, homeobox; NPM1, nucleophosmin; wt, wild type.