Table 1.

Investigational strategies for targeting AML with mutated NPM1.

	Drug Class	Target	Mechanism	References
ATRA + ATO	Antineoplastic agents	?	Proteasomal degradation of NPM1	Martelli et al., 2015; El Hajj et al., 2015
Dactinomycin	Chemotherapy	RNA-Pol 1	Unclear in this setting	Falini et al., 2015
GO	ADC	CD33	Induces DSBs in DNA, cell cycle Arrest and apoptosis	Lambert et al., 2014; Olombel et al., 2016
Venetoclax	Small molecule	Bcl-2	Induces apoptosis	Lachowiez et al., 2020
Selinexor	Small molecule	XPO1	Inhibits translocation of NPM1 to the cytoplasm	Brunetti et al., 2019
EAPB0503	Small molecule	?	Proteasomal degradation of NPM1	Nabbouh et al., 2017
Modified T cells	Immunotherapy	Neoantigen	T-cell activation	Van der Lee et al., 2019
VTP-50469	Small molecule	Menin	Disrupts MLL chromatin complex Preferential effect on MEIS1 (not HOX)	Uckelman et al., 2020
MI-2, MI-503, MI-463, MI-3454	Small molecule	Menin	Inhibits HOX genes and MEIS1	Borkin et al., 2015; Grembecka et al., 2012; Krivtsov et al. 2019
Deguelin	Rotenoid	?	Induces apoptosis in NPM1c cell lines	Yi et al., 2015
NSC348884	Small molecule	NPM1 Oligomerization domain	Inhibits oligomerization, leading to apoptosis	Balusa et al., 2011

Abbreviations: ATRA + ATO, all-trans retinoic acid with arsenic trioxide; GO, Gemtuzumab ozogamicin; ADC, antibody-drug conjugate. GO is an IgG4 κ antibody bound to calicheamicin. DSBs: double-stranded breaks. Targets of EAPB0503 and Deguelin are unknown.