| First Author | Pollock JL | Year | 1999 |
| Journal | Proc Natl Acad Sci U S A | Volume | 96 |
| Issue | 26 | Pages | 15103-8 |
| PubMed ID | 10611345 | Mgi Jnum | J:59080 |
| Mgi Id | MGI:1350874 | Doi | 10.1073/pnas.96.26.15103 |
| Citation | Pollock JL, et al. (1999) A bcr-3 isoform of RARalpha-PML potentiates the development of PML-RARalpha-driven acute promyelocytic leukemia. Proc Natl Acad Sci U S A 96(26):15103-8 |
| abstractText | Acute promyelocytic leukemia (APML) most often is associated with the balanced reciprocal translocation t(15;17) (q22;q11.2) and the expression of both the PML-RARalpha and RARalpha-PML fusion cDNAs that are formed by this translocation. In this report, we investigated the biological role of a bcr-3 isoform of RARalpha-PML for the development of APML in a transgenic mouse model. Expression of RARalpha-PML alone in the early myeloid cells of transgenic mice did not alter myeloid development or cause APML, but its expression significantly increased the penetrance of APML in mice expressing a bcr-1 isoform of PML-RARalpha (15% of animals developed APML with PML-RARalpha alone vs. 57% with both transgenes, P < 0.001). The latency of APML development was not altered substantially by the expression of RARalpha-PML, suggesting that it does not behave as a classical 'second hit' for development of the disease. Leukemias that arose from doubly transgenic mice were less mature than those from PML-RARalpha transgenic mice, but they both responded to all-trans retinoic acid in vitro. These findings suggest that PML-RARalpha drives the development of APML and defines its basic phenotype, whereas RARalpha-PML potentiates this phenotype via mechanisms that are not yet understood. |
