“FLipping” the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors
Abstract
:Simple Summary
Abstract
1. Introduction
2. The FLT3 Receptor
3. FLT3 Mutations
3.1. Internal Tandem Duplications
3.2. Mutations within the Tyrosine Kinase Domain
3.3. Non-ITD, Non-TKD FLT3 Mutations
3.4. All ITD Mutations Are not Created Equal
3.4.1. Allelic Ratio
3.4.2. Mutation Length
3.4.3. Co-Occurring Mutations
3.5. Implications of FLT3 Mutations for AML Risk Categorization
4. Clinical Implementation of FLT3 Inhibitors in Adult Clinical Trials
4.1. First Generation, Type 1 FLT3 Inhibitors
4.1.1. Midostaurin
4.1.2. Lestaurtinib
4.1.3. Sunitinib
4.2. First Generation, Type 2 FLT3 Inhibitors
4.2.1. Sorafenib
4.2.2. Pexidartinib
4.2.3. Ponatinib
4.3. Second Generation, Type 1 FLT3 Inhibitors
4.3.1. Gilteritinib
4.3.2. Crenolanib
4.3.3. MRX-2843
4.4. Second Generation, Type 2 FLT3 Inhibitors
Quizartinib
5. FLT3 Inhibition in Pediatric FLT3-Mutated AML
6. CD33+ Targeting, Consolidative HSCT, and Integration of FLT3 Inhibition
7. Resistance to FLT3 Inhibition—And How to Overcome It
7.1. Intrinsic Mechanisms of Resistance
7.2. Emergent Mechanisms of Resistance
8. Conclusions and Future Directions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Type 1 FLT3 Inhibitors (Inhibition of Both Active and Inactive FLT3 Confirmation) | Type 2 FLT3 Inhibitors (Inhibition of Inactive Conformation Only) | |
---|---|---|
First Generation FLT3 Inhibitors | * Midostaurin [80,81,82,83] Lestaurtinib [84,85] Sunitinib [86] | Sorafenib [87,88,89,90] Pexidartinib [91] Ponatinib [92,93,94,95] |
Second Generation FLT3 Inhibitors | ** Gilteritinib [96,97,98,99,100,101] Crenolanib [67,102,103,104,105] MRX-2843 [106,107,108] | Quizartinib [109,110] |
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Knight, T.E.; Edwards, H.; Meshinchi, S.; Taub, J.W.; Ge, Y. “FLipping” the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors. Cancers 2022, 14, 3398. https://doi.org/10.3390/cancers14143398
Knight TE, Edwards H, Meshinchi S, Taub JW, Ge Y. “FLipping” the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors. Cancers. 2022; 14(14):3398. https://doi.org/10.3390/cancers14143398
Chicago/Turabian StyleKnight, Tristan E., Holly Edwards, Soheil Meshinchi, Jeffrey W. Taub, and Yubin Ge. 2022. "“FLipping” the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors" Cancers 14, no. 14: 3398. https://doi.org/10.3390/cancers14143398