A bcr-3 isoform of RARalpha- PML potentiates the development of PML-RARalpha-driven acute promyelocytic leukemia.
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.[1]References
- A bcr-3 isoform of RARalpha-PML potentiates the development of PML-RARalpha-driven acute promyelocytic leukemia. Pollock, J.L., Westervelt, P., Kurichety, A.K., Pelicci, P.G., Grisolano, J.L., Ley, T.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
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