B-ALL Complexity: Is Targeted Therapy Still A Valuable Approach for Pediatric Patients?
Abstract
:Simple Summary
Abstract
1. Introduction
2. Aneuploidy B-ALL
2.1. Hypodiploidy
2.2. Hyperdiploidy
3. Ph-Like B-ALL
4. iAMP21 B-ALL
5. MEF2D-Rearranged B-ALL
6. ZNF384-Rearranged B-ALL
7. DUX4-Rearranged B-ALL
8. Pax5-Driven B-ALL
8.1. PAX5alt
8.2. PAX5 P80R
9. ETV6-RUNX1-Like B-ALL
10. NUTM1 Rearranged B-ALL
11. Targetable Signaling Pathways in B-ALL
11.1. Ras
11.2. PI3K/Akt/mTOR Signaling
11.3. Ras/MEK/ERK Signaling
11.4. Wnt/β-Catenin Signaling Pathway
11.5. Bcl2
11.6. BET Proteins
11.7. HDAC
11.8. JAK/STAT
11.9. ABL1 Kinase
12. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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B-ALL Subtype | Prognosis | Altered Signaling Pathways | Target | Ref |
---|---|---|---|---|
MEF2D | Unfavorable/Intermediate | Ras/MEK/ERK, Wnt/β-catenin | HDAC | [47] |
ZNF384 | Intermediate | Ras, JAK/STAT | HDAC | [56] |
DUX4 | Very Favorable | Ras | [63] | |
Hypodiploidy | Unfavorable/Intermediate | Ras, PI3K/Akt/mTOR | Bcl2 | [6] |
Hyperdiploidy | Very Favorable | Ras/MEK/ERK | MEK | [8] |
Pax5 alt | Intermediate | c-myc | BET | [73] |
Pax5 P80R | Favorable | Ras, c-myc, IL7 | [80] | |
Ph-like | Unfavorable | JAK/STAT, ABL1, Ras, PI3K/Akt/mTOR/IL7 | mTOR, JAK | [25] |
ETV6-RUNX1-like | Favorable | ABL1 | [25] | |
NUTM1 | Very Favorable | c-myc | BET | [88] |
iAMP21 | Intermediate | Ras/MEK/ERK | MEK | [42] |
Drug | Target | Disease | Clinical Trials |
---|---|---|---|
Everolimus | mTOR | Pediatric ALL | NCT01523994 |
Selumetinib | MEK1/2 | Pediatric ALL | NCT03705507 |
PRI-724 | β-catenin | Hematogical malignancies | NCT01606579 NCT02195440 |
Venetoclax | Bcl2 | Pediatric ALL | NCT03504644 NCT04029688 NCT03236857 |
Molibresib | BET proteins | Hematogical malignancies | NCT01943851 |
OTX015 | BET proteins | Hematogical malignancies | NCT01713582 |
Panobistat | HDAC | Pediatric ALL | NCT01321346 NCT02518750 |
Entinostat | HDAC | B-ALL | NCT01383447 |
Vorinostat | HDAC | Pediatric ALL | NCT02553460 NCT01312818 |
Ruxolinib | JAK/STAT | Pediatric ALL | NCT02723994 NCT02420717 NCT03117751 |
Dasatinib | ABL1 | Pediatric Ph-like ALL | NCT03117751 NCT02420717 NCT01406756 |
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Ratti, S.; Lonetti, A.; Follo, M.Y.; Paganelli, F.; Martelli, A.M.; Chiarini, F.; Evangelisti, C. B-ALL Complexity: Is Targeted Therapy Still A Valuable Approach for Pediatric Patients? Cancers 2020, 12, 3498. https://doi.org/10.3390/cancers12123498
Ratti S, Lonetti A, Follo MY, Paganelli F, Martelli AM, Chiarini F, Evangelisti C. B-ALL Complexity: Is Targeted Therapy Still A Valuable Approach for Pediatric Patients? Cancers. 2020; 12(12):3498. https://doi.org/10.3390/cancers12123498
Chicago/Turabian StyleRatti, Stefano, Annalisa Lonetti, Matilde Y. Follo, Francesca Paganelli, Alberto M. Martelli, Francesca Chiarini, and Camilla Evangelisti. 2020. "B-ALL Complexity: Is Targeted Therapy Still A Valuable Approach for Pediatric Patients?" Cancers 12, no. 12: 3498. https://doi.org/10.3390/cancers12123498