Pim2 cooperates with PML-RARα to induce acute myeloid leukemia in a bone marrow transplantation model
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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 promyelocytic leukemia/retinoic acid receptor α (PML/RARα), we used a well-established PML-RARα (PRα) mouse model. Pim2 coexpression in PRα-positive hematopoietic progenitor cells (HPCs) induces leukemia in recipient mice after a short latency. Pim2-PRα cells were able to repopulate mice in serial transplantations and to induce disease in all recipients. Neither Pim2 nor PRα alone was sufficient to induce leukemia upon transplantation in this model. The disease induced by Pim2 overexpression in PRα cells contained a slightly higher fraction of immature myeloid cells, compared with the previously described APL disease induced by PRα. However, it also clearly resembled an APL-like phenotype and showed signs of differentiation upon all-trans retinoic acid (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-RARα), cooperates with PRα to induce APL-like disease.
Date Issued
2010-06-03
Date Acceptance
2010-01-18
Citation
Blood, 2010, 115 (22), pp.4507-4516
ISSN
0006-4971
Publisher
American Society of Hematology
Start Page
4507
End Page
4516
Journal / Book Title
Blood
Volume
115
Issue
22
Copyright Statement
"This research was originally published in Blood. Shuchi Agrawal-Singh, Steffen Koschmieder, Sandra Gelsing, Carol Stocking, Martin Stehling, Christian Thiede, Nils H. Thoennissen, Gabriele Köhler, Peter J. M. Valk, Ruud Delwel, Ken Mills, Nicole Bäumer, Lara Tickenbrock, Klaus Hansen, Wolfgang E. Berdel, Carsten Müller-Tidow, Hubert Serve; Pim2 cooperates with PML-RARα to induce acute myeloid leukemia in a bone marrow transplantation model. Blood 2010; 115 (22): 4507–4516. doi: https://doi.org/10.1182/blood-2009-03-210070. © the American Society of Hematology."
Identifier
10.1182/blood-2009-03-210070
Publication Status
Published
Date Publish Online
2010-03-09