Pim2 cooperates with PML-RAR{alpha} to induce acute myeloid leukemia in a bone marrow transplantation model.
Department of Medicine, Hematology and Oncology, University of Muenster, Muenster, Germany;
Although the potential role of Pim2 as a cooperative oncogene has been well described in lymphoma, its role in leukemia has remained largely unexplored. Here we show that high expression of Pim2 is observed in patients with acute promyelocytic leukemia (APL). To further characterize the cooperative role of Pim2 with PML-RARalpha, we used a well-established PML-RARalpha (PRalpha) mouse model. Pim2 coexpression in PRalpha-positive hematopoietic progenitor cells (HPC) induces leukemia in recipient mice after a short latency. Pim2/PRalpha cells were able to repopulate mice in serial transplantations and to induce disease in all of these recipients. Neither Pim2 nor PRalpha alone were sufficient to induce leukemia upon transplantation in this model. The disease induced by Pim2 over-expression in PRalpha cells contained a slightly higher fraction of immature myeloid cells, when compared to the previously described APL disease induced by PRalpha. However, it also clearly resembled an APL-like phenotype and showed signs of differentiation upon ATRA treatment in vitro. These results support the hypothesis that Pim2, which is also a known target of Flt3-ITD (another gene that cooperates with PML-RARalpha), cooperates with PRalpha to induce APL-like disease.
PMID: 20215640 [PubMed - as supplied by publisher]
PMID: 20215640 [PubMed - as supplied by publisher]
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