Genetic insights into targeted therapy
. | Potential therapy . |
|---|---|
| Signal transduction pathways | |
| Mutation | |
| FLT3 | |
| Activation loop* | Small molecule FLT3 inhibitors |
| ITD† | Small molecule FLT3 inhibitors |
| RAS‡ | Farnesyl transferase inhibitors |
| PTPN11 (SHP2)§ | — |
| BCR-ABL§ | Imatinib mesylate |
| TEL-PDGFβR§ | Imatinib mesylate |
| ZNF198-FGFR1§ | Small molecule FGFR inhibitors |
| Downstream effectors | |
| mTOR | Rapamycin |
| MEK | Small molecule inhibitors |
| P13/AKT | Small molecule inhibitors |
| Differentiation pathways: mutation | |
| PML-RARα | ATRA, arsenic |
| Core binding factor | |
| RUNX1-ETO | HDAC inhibitors |
| CBFβ-MYH11 | HDAC inhibitors |
| MLL fusions | HDAC inhibitors/differentiating agents |
| Coactivator fusions | HDAC inhibitors/differentiating agents |
| MLL-CBP, MOZ-TIF2, RUNX1, GATA-1, CEBPA, PU.1 | Differentiating agents |
| Self-renewal pathway/gene | |
| WNT/β-catenin | Unknown |
| Notch | Unknown |
| BMI-1 | Unknown |
| HOX genes | Unknown |
. | Potential therapy . |
|---|---|
| Signal transduction pathways | |
| Mutation | |
| FLT3 | |
| Activation loop* | Small molecule FLT3 inhibitors |
| ITD† | Small molecule FLT3 inhibitors |
| RAS‡ | Farnesyl transferase inhibitors |
| PTPN11 (SHP2)§ | — |
| BCR-ABL§ | Imatinib mesylate |
| TEL-PDGFβR§ | Imatinib mesylate |
| ZNF198-FGFR1§ | Small molecule FGFR inhibitors |
| Downstream effectors | |
| mTOR | Rapamycin |
| MEK | Small molecule inhibitors |
| P13/AKT | Small molecule inhibitors |
| Differentiation pathways: mutation | |
| PML-RARα | ATRA, arsenic |
| Core binding factor | |
| RUNX1-ETO | HDAC inhibitors |
| CBFβ-MYH11 | HDAC inhibitors |
| MLL fusions | HDAC inhibitors/differentiating agents |
| Coactivator fusions | HDAC inhibitors/differentiating agents |
| MLL-CBP, MOZ-TIF2, RUNX1, GATA-1, CEBPA, PU.1 | Differentiating agents |
| Self-renewal pathway/gene | |
| WNT/β-catenin | Unknown |
| Notch | Unknown |
| BMI-1 | Unknown |
| HOX genes | Unknown |
ITD indicates internal tandem duplication; RAS, retinoic acid syndrome; PTPN11, protein tyrosine phosphatase, nonreceptor type 11; SHP2, Src homology 2 phosphatase 2; BCR-ABL, breakpoint cluster region-Abelson; TEL-PDGFβR, telomere elongation-platelet-derived growth factor β receptor; ZNF198-FGFR1, zinc finger protein 198-fibroblast growth factor receptor 1; mTOR, mammalian target of rapamycin; MEK, mitogen-activated protein kinase kinase; PI3/AKT, phosphatidylinositol 3/protein kinase B; RUNX1-ETO, runt-related transcription factor 1-eight-twenty-one; HDAC, histone deacetylase; CBFβ-MYH11, core-binding factor β-myosin, heavy polypeptide 11; MLL, mixed lineage leukemia; CREB (cAMP [cyclic adenosine monophosphate] response element-binding protein)-binding protein; MOZ-TIF2, monocytic leukemia zinc finger protein-translational initiation factor 2; GATA-1, GATA binding protein 1; C/EBPA, CCAAT/enhancer binding protein α; WNT, Wingless-type.
Occurrence is ∼ 5%-10%.
Occurrence is ∼ 20%-25%.
Occurrence is ∼ 10%-15%.
Occurrence is rare.