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Functional role of BAALC in leukemogenesis

Leukemia volume 26, pages 532–536 (2012)Cite this article

High expression of BAALC in cytogenetically normal-acute myeloid leukemia (AML) patients is associated with primary resistant disease, shorter relapse-free, disease-free and overall survival.1, 2, 3, 4 However, there is no published data evaluating the role of BAALC in the hematopoietic system. BAALC is located on human chromosome 8q22.3 and is highly conserved in mammals. High BAALC expression levels were first identified in a study of AML patients with trisomy 8 as a sole abnormality,5 and was shown to correlate highly with MN1 expression,6, 7 a potent oncogene in leukemogenesis.8 Several isoforms of BAALC have been described with isoform 2 (also known as 1-6-8) being the most abundant in the brain and in AML samples.5

This finding stimulated us to further investigate whether BAALC was upregulated as a consequence of MN1 upregulation or vice versa. Retroviral overexpression of human full-length MN1 in a murine model system induces rapid-onset AML.8, 9 We used murine BM cell lines immortalized by retroviral expression of Hoxa9 or NUP98HOXD13, and co-transduced these cells with full-length MN1 or a control vector as described before.10 Baalc expression was not increased but rather decreased in MN1-expressing NUP98HOXD13 cells as compared with control transduced NUP98HOXD13 cells (Figure 1b). Baalc expression decreased in BM cells that were freshly transduced with MN1 or Hoxa9 compared with control transduced BM cells (Figure 1c). Analogous experiments in which BAALC overexpression was engineered in NUP98HOXD13 or Hoxa9 cells did not reveal a positive correlation with Mn1 expression (Figure 1d). Mn1 expression was not influenced by transduction of BAALC in freshly isolated BM cells, but was increased by transduction of human MN1 and decreased by transduction of Hoxa9 in freshly isolated BM cells (Figure 1e, see Supplementary Table S1 for primer sequences). Thus, it appears unlikely that MN1 and/or BAALC cross-regulate each other. Rather, dysregulation of a common upstream regulatory mechanism may be responsible for the observed coordinated upregulation in human AML cells.

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Acknowledgements

We are indebted to the patients participating in this study and the members of the AML-SHG Study Group for providing leukemia specimens. This study was supported by grants from the Terry Fox Foundation, Canada, the Cancer Research Society, Canada, grant No. 109003 from the Deutsche Krebshilfe e.V., grant No. DJCLS R 10/22 from the Deutsche-José-Carreras Leukämie-Stiftung e.V. and grant No. M 47.1 from the HW & J Hector Stiftung. TB was supported by the Deutsche Forschungsgemeinschaft (Bonn, Germany; grant no. BE4198/1–1).

Author contributions

MH, TB, AG and RKH designed the research; MH, TB, FK, GP, SF, GL, ML, CL and JK performed the research; MH, TB, GL and RKH analyzed the data; and MH, TB and RKH wrote the paper. All authors checked the final version of the manuscript.

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  1. M Heuser and T Berg: These authors contributed equally to this work.

Authors and Affiliations

  1. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada

    M Heuser, T Berg, F Kuchenbauer, C K Lai, G Park, S Fung, G Lin, M Leung & R K Humphries

  2. Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    M Heuser, J Krauter & A Ganser

  3. Department of Internal Medicine III, University Hospital Medical Center, Ulm, Germany

    F Kuchenbauer

  4. Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

    R K Humphries

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Correspondence to R K Humphries.

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Heuser, M., Berg, T., Kuchenbauer, F. et al. Functional role of BAALC in leukemogenesis. Leukemia 26, 532–536 (2012). https://doi.org/10.1038/leu.2011.228

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