Abstract
MicroRNA-125b-1 (miR-125b-1) is a target of the chromosomal translocations t(11;14)(q24;q32) and t(2;11)(p21;q23), which are found in human B-lymphoid and myeloid malignancies, respectively. These translocations result in overexpression of mature miR-125b, consisting of 22 nucleotides. To analyze the role of miR-125b-1 in leukemogenesis, we created a bone marrow transplantation model using a retrovirus vector containing GFP expression elements. Sole transduction of miR-125b-1 into bone marrow cells resulted in expansion of hematopoietic cells expressing GFP. Compared with cells lacking GFP expression, we observed that GFP+/CD11b+ or GFP+/Gr−1+ cells were increased in the bone marrow and spleen. Although previous studies reported sole induction of miR-125b-induced leukemia, we did not find leukemic transformation in our model. Transduction of miR-125b-1 did accelerate myeloid tumors induced by a C-terminal mutant of CAAT-enhancer binding protein (C/EBPα-Cm), a class II-like mutation. As miR-125b has been shown to hasten the development of leukemia in a BCR/ABL-transduced animal model, our present results support the conclusion that overexpression of miR-125b cooperates with other genetic alterations in the pathogenesis of myeloid malignancies.
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Acknowledgments
This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan, and was supported in part by a Grant-in-Aid for Scientific Research on Innovative Areas, Global COE Program “Center of Education and Research for Advanced Genome-Based Medicine—For personalized medicine and the control of worldwide infectious diseases”, MEXT, Japan, a Grant for Basic and Clinical Research Project from Osaka Cancer Research Foundation 2008, a Research Grant on Priority Areas from Wakayama Medical University 2008, and a grant from the Japan Society for the Promotion of Science (JSPS). This work was performed as part of the Cooperative Research Project of the Institute of Medical Science, Tokyo University. Y. Enomoto is a JSPS research fellow.
Conflict of interest
T.K. serves as a consultant for R&D Systems. The remaining authors declare no competing financial interests.
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Supplementary material 1 (PPT 540 kb). Supplemental data include the characterization of peripheral blood cells by FACS 5 weeks after BMT
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Enomoto, Y., Kitaura, J., Shimanuki, M. et al. MicroRNA-125b-1 accelerates a C-terminal mutant of C/EBPα (C/EBPα-Cm)-induced myeloid leukemia. Int J Hematol 96, 334–341 (2012). https://doi.org/10.1007/s12185-012-1143-5
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DOI: https://doi.org/10.1007/s12185-012-1143-5