Genetic lesions found in advanced-phase CML.
| Genetic lesion . | Mechanism . | Functional effects . |
|---|---|---|
| The table above is not meant to be inclusive of all genes either known or implicated in blast crisis biology, but rather an example the genes involved, the mechanisms causing their deregulation, and their biological consequence. The table draws influence from many papers, but most recently from the more exhaustive approach by Melo and Barnes.8 | ||
| Chromosomal | ||
| Bcr-Abl | Amplification | Almost everything |
| NUP98-HOXA9, AML1-EVI1 | Translocation | Differentiation |
| TP53 | Deletion | Tumor suppressor |
| P16/ARF | Deletion | Proliferation |
| Point mutations | ||
| TP53 | Point mutation | Tumor suppressor |
| Expression/translation | ||
| CEBPA | Translational block | Differentiation |
| hnENPE2 | Increased expression | Differentiation |
| PP2A | Inhibition by SET | Tumor suppressor |
| Bcl2 | Increased expression | Apoptosis |
| FOXO3A | Decreased expression | Apoptosis |
| JunB | Decreased expression | Transcriptional regulation |
| WT1 | Increased expression | Proliferation |
| BMI1 | Increased expression | Proliferation |
| Genetic lesion . | Mechanism . | Functional effects . |
|---|---|---|
| The table above is not meant to be inclusive of all genes either known or implicated in blast crisis biology, but rather an example the genes involved, the mechanisms causing their deregulation, and their biological consequence. The table draws influence from many papers, but most recently from the more exhaustive approach by Melo and Barnes.8 | ||
| Chromosomal | ||
| Bcr-Abl | Amplification | Almost everything |
| NUP98-HOXA9, AML1-EVI1 | Translocation | Differentiation |
| TP53 | Deletion | Tumor suppressor |
| P16/ARF | Deletion | Proliferation |
| Point mutations | ||
| TP53 | Point mutation | Tumor suppressor |
| Expression/translation | ||
| CEBPA | Translational block | Differentiation |
| hnENPE2 | Increased expression | Differentiation |
| PP2A | Inhibition by SET | Tumor suppressor |
| Bcl2 | Increased expression | Apoptosis |
| FOXO3A | Decreased expression | Apoptosis |
| JunB | Decreased expression | Transcriptional regulation |
| WT1 | Increased expression | Proliferation |
| BMI1 | Increased expression | Proliferation |