Could Targeting NPM1c+ Misfolding Be a Promising Strategy for Combating Acute Myeloid Leukemia?
Abstract
1. Introduction
2. Structure and Functions of NPM1
3. NPM1 Is the Most Commonly Mutated Gene in Adult AML
3.1. Common NPM1 Mutations and Structural Consequences
3.2. Rare Mutations of Exon 5 and Fusion Transcripts of NPM1c+
3.3. Consequences of Cytoplasmic Mislocation of NPM1c+
4. NPM1c+ Mutations Govern the Amyloidogenicity of the CTD
5. Therapeutic Strategies Targeting NPM1c+
5.1. Therapeutics Targeting NPM1 Protein–Protein Interactions
5.2. Therapeutics Targeting the Nucleolus of NPM1c+
5.3. Therapeutics Targeting NPM1c+ Localization
5.4. Therapeutics as Menin Inhibitors
5.5. Therapeutics Targeting Aggregation of NPM1c+
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Nucleotide Sequence | Protein | |
---|---|---|
wt NPM1 | GATCTCTG…GCAGT…GGAGGAAGTCTCTTTAAGAAAATAG | 286DLWQWRKSL294 |
Common mutations | GATCTCTGTCTGGCAGT…GGAGGAAGTCTCTTTAAGAAAATAG | 286DLCLAVEEVSLRK298 |
GATCTCTGCATGGCAGT…GGAGGAAGTCTCTTTAAGAAAATAG | 286DLCMAVEEVSLRK298 | |
GATCTCTGCGTGGCAGT…GGAGGAAGTCTCTTTAAGAAAATAG | 286DLCVAVEEVSLRK298 | |
GATCTCTGCCTGGCAGT…GGAGGAAGTCTCTTTAAGAAAATAG | 286DLCLAVEEVSLRK298 | |
GATCTCTG…GCAGTCTCTTGCCCAAGTCTCTTTAAGAAAATAG | 286DLWQSLAQVSLRK298 | |
GATCTCTG…GCAGTCCCTGGAGAAAGTCTCTTTAAGAAAATAG | 286DLWQSLEKVSLRK298 | |
GATCTCTG…GCAGTCTCTTTCTAAAGTCTCTTTAAGAAAATAG | 286DLWQSLSKVSLRK298 | |
GATCTCTCCCGGGCAGT…AAGTCTCTTTAAGAAAATAG | 286DLSRAVEEVSLRK298 | |
GATCTCTG…GCAGTCCCTTTCCAAAGTCTCTTTAAGAAAATAG | 286DLWQSLSKVSLRK298 | |
GATCTCTGTAGCGCAGT…GGAGGAAGTCTCTTTAAGAAAATAG | 286DLCTAVEEVSLRK298 | |
GATCTCTGCCACGCAGT…GGAGGAAGTCTCTTTAAGAAAATAG | 286DLCHAVEEVSLRK298 | |
GATCTCTGGCAGCGTTTCCAGGAAGTCTCTTTAAGAAAATAG | 286DLWQRFQEVSLRK298 | |
GATCTCTGTACCTTCCT…GGAGGAAGTCTCTTTAAGAAAATAG | 286DLCTFLEEVSLRK298 | |
GATCTCTG…GCAGAGGATGGAGGAAGTCTCTTTAAGAAAATAG | 286DLWQRMEEVSLRK298 | |
Nucleotide Change | ||
Rare mutations | c.864_876delinsTCGGAGTCTCGGCGGAC | 286DLCRSLGGLSLRKA299 |
c.864_873delinsTCAAGACTTTCTTA | 286DLCQDFLKVSLRKA299 | |
c.867_875delinsAGATTTCTTAAATC | 286DLWQDFLNRLFKRIVA301 | |
c.868_876delinsGGGATAGCGATGC | 286DLWQGIAMLSLRKA299 | |
c.868_876delinsGGGGTGGGGAATC | 286DLWQGVGNLSLRKA299 | |
c.863_871delinsCGACCCTCCTGGG | 286DLSTLLGEVSLRKA299 |
In-Frame Insertion/Duplications | Protein | |
---|---|---|
Exon 5 Mutations | c408–409 (F,5′-GCGGAGGATGTGAAACTCTTA) | DVKLL136AEDVKLL…286DLWQWRKSL294 |
c409–410 (F,5′-AATGATCTGTCACTTCTG) | DVKLL137K | |
c424–425 (F,5′-TTTCTGCCTTAAGTATATCTGGAAAGC) | ISGK141LSALSISGK…286DLWQWRKSL294 | |
c399–400 (F,5′-CAACTCTTA) and c400–401 (F,5′-GTGGGCTGC) | EEDV134QLLSGLQ…286DLWQWRKSL294 | |
c406–423 (F,5′-GCCCTGGAACTGGGGAAC) | DVKL135ALELGNLSI…286DLWQWRKSL294 |
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Florio, D.; Marasco, D. Could Targeting NPM1c+ Misfolding Be a Promising Strategy for Combating Acute Myeloid Leukemia? Int. J. Mol. Sci. 2024, 25, 811. https://doi.org/10.3390/ijms25020811
Florio D, Marasco D. Could Targeting NPM1c+ Misfolding Be a Promising Strategy for Combating Acute Myeloid Leukemia? International Journal of Molecular Sciences. 2024; 25(2):811. https://doi.org/10.3390/ijms25020811
Chicago/Turabian StyleFlorio, Daniele, and Daniela Marasco. 2024. "Could Targeting NPM1c+ Misfolding Be a Promising Strategy for Combating Acute Myeloid Leukemia?" International Journal of Molecular Sciences 25, no. 2: 811. https://doi.org/10.3390/ijms25020811
APA StyleFlorio, D., & Marasco, D. (2024). Could Targeting NPM1c+ Misfolding Be a Promising Strategy for Combating Acute Myeloid Leukemia? International Journal of Molecular Sciences, 25(2), 811. https://doi.org/10.3390/ijms25020811