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.
A bcr-3 isoform of RARalpha-PML potentiates the development of PML-RARalpha-driven acute promyelocytic leukemia / J. L. Pollock, P. Westervelt, A. K. Kurichety, P. G. Pelicci, J. L. Grisolano, T. J. Ley. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 96:26(1999 Dec 21), pp. 15103-8-15108.
|Titolo:||A bcr-3 isoform of RARalpha-PML potentiates the development of PML-RARalpha-driven acute promyelocytic leukemia|
|Parole Chiave:||Animals; Humans; Gene Expression; Spleen; Mice; Cathepsins; Mice, Transgenic; Protein Isoforms; Translocation, Genetic; Phenotype; Bone Marrow Cells; Neoplasm Proteins; Penetrance; Leukemia, Promyelocytic, Acute; Tretinoin; Crosses, Genetic; Oncogene Proteins, Fusion|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||21-dic-1999|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1073/pnas.96.26.15103|
|Appare nelle tipologie:||01 - Articolo su periodico|