Publication details
PML-RAR alpha co-operates with Sox4 in acute myeloid leukemia development in mice
| Authors | |
|---|---|
| Year of publication | 2013 |
| Type | Article in Periodical |
| Magazine / Source | Haematologica-The Hematology Journal |
| MU Faculty or unit | |
| Citation | |
| Web | http://www.haematologica.org/content/98/3/424.full.pdf+html |
| Doi | http://dx.doi.org/10.3324/haematol.2011.057067 |
| Field | Oncology and hematology |
| Keywords | Acute promyelocytic leukemia; PML-RAR alpha; SOX4; mice |
| Attached files | |
| Description | Acute promyelocytic leukemia is characterized by a chromosomal translocation involving the retinoic acid receptor alpha gene. To identify cooperating pathways to leukemogenesis we crossed MRP8-PML/RARA transgenic mice with BXH-2 mice, which harbor an endogenous murine leukemia virus that causes acute myeloid leukemia. Approximately half of leukemias that arose in this cross showed features of acute promyelocytic leukemia. We identified 22 proviral insertions sites in acute promyelocytic-like leukemias and focused our analysis on insertion at Sox4, a HMG box transcription factor. Using a transplant model, cooperation between PML-RARalpha and Sox4 was confirmed with increased penetrance and reduced latency of disease. Interestingly, karyotypic analysis revealed cytogenetic changes suggesting that the factors combined to initiate but not complete leukemic transformation. The cooperation between these transcription factors is consistent with the paradigm of multiple routes to the disease and reinforces the concept that transcription factor networks are important therapeutic targets in myeloid leukemias. |