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WTAP is a novel oncogenic protein in acute myeloid leukemia

Leukemia volume 28, pages 1171–1174 (2014)Cite this article

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A Corrigendum to this article was published on 10 December 2014

The biology of acute myelogenous leukemia (AML) is characterized by a block in differentiation, increase in proliferation and inhibition of apoptosis, all of which when combined lead to an expansion of leukemic blasts.1 AML therapy cures ∼20% of those affected,2 highlighting the need for a better understanding of leukemia biology in order to identify novel therapeutic targets.

To examine the role of WTAP in AML progression in vivo, we performed tumor xenograft experiments in nude mice. As shown in Figure 1f, the growth rates and masses of tumors derived from WTAP-knockdown cells were significantly reduced (P⩽0.01) compared with control. To complement this analysis, the in vitro transforming activity of WTAP was examined by investigating its effects on growth of the Ba/F3 cell line. This line depends on interleukin 3 (IL-3) for survival and proliferation, but this dependence can be released by the transgenic expression of suitable oncogenes.9 Whereas control Ba/F3 cells were not viable in the absence of IL-3 at 72 h, WTAP-expressing Ba/F3 cells were able to maintain growth factor-independent proliferation, as demonstrated by significantly higher (P⩽0.01) number of viable cells (Figure 1g), suggesting that WTAP harbors oncogenic activity.

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References

  1. Estey E, Dohner H . Acute myeloid leukaemia. Lancet 2006; 368: 1894–1907.

    Article  PubMed  Google Scholar 

  2. Tallman MS, Gilliland DG, Rowe JM . Drug therapy for acute myeloid leukemia. Blood 2005; 106: 1154–1163.

    Article  CAS  PubMed  Google Scholar 

  3. Sugiyama H . WT1 (Wilms’ tumor gene 1): biology and cancer immunotherapy. Jpn J Clin Oncol 2010; 40: 377–387.

    Article  PubMed  Google Scholar 

  4. Little NA, Hastie ND, Davies RC . Identification of WTAP, a novel Wilms’ tumour 1-associating protein. Hum Mol Genet 2000; 9: 2231–2239.

    Article  CAS  PubMed  Google Scholar 

  5. Penalva LO, Ruiz MF, Ortega A, Granadino B, Vicente L, Segarra C et al. The Drosophila fl(2)d gene, required for female-specific splicing of Sxl and tra pre-mRNAs, encodes a novel nuclear sprotein with a HQ-rich domain. Genetics 2000; 155: 129–139.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Small TW, Penalva LO, Pickering JG . Vascular biology and the sex of flies: regulation of vascular smooth muscle cell proliferation by Wilms’ tumor 1-associating protein. Trends Cardiovasc Med 2007; 17: 230–234.

    Article  CAS  PubMed  Google Scholar 

  7. Horiuchi K, Umetani M, Minami T, Okayama H, Takada S, Yamamoto M et al. Wilms’ tumor 1-associating protein regulates G2/M transition through stabilization of cyclin A2 mRNA. Proc Natl Acad Sci USA 2006; 103: 17278–17283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jin DI, Lee SW, Han ME, Kim HJ, Seo SA, Hur GY et al. Expression and roles of Wilms’ tumor 1-associating protein in glioblastoma. Cancer Sci 2012; 103: 2102–2109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Daley GQ, Baltimore D . Transformation of an interleukin 3-dependent hematopoietic cell line by the chronic myelogenous leukemia-specific P210bcr/abl protein. Proc Natl Acad Sci USA 1988; 85: 9312–9316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rosenbauer F, Tenen DG . Transcription factors in myeloid development: balancing differentiation with transformation. Nat Rev Immunol 2007; 7: 105–117.

    Article  CAS  PubMed  Google Scholar 

  11. Park S, Chapuis N, Tamburini J, Bardet V, Cornillet-Lefebvre P, Willems L et al. Role of the PI3K/AKT and mTOR signaling pathways in acute myeloid leukemia. Haematologica 2010; 95: 819–828.

    Article  CAS  PubMed  Google Scholar 

  12. The Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013; 368: 2059–2074.

    Article  PubMed Central  Google Scholar 

  13. Whitesell L, Lindquist SL . HSP90 and the chaperoning of cancer. Nat Rev Cancer 2005; 5: 761–772.

    Article  CAS  PubMed  Google Scholar 

  14. Bansal H, Bansal S, Rao M, Foley KP, Sang J, Proia DA et al. Heat shock protein 90 regulates the expression of Wilms tumor 1 protein in myeloid leukemias. Blood 2010; 116: 4591–4599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rao R, Fiskus W, Yang Y, Lee P, Joshi R, Fernandez P et al. HDAC6 inhibition enhances 17-AAG—mediated abrogation of hsp90 chaperone function in human leukemia cells. Blood 2008; 112: 1886–1893.

    Article  CAS  PubMed  Google Scholar 

  16. Ying W, Du Z, Sun L, Foley KP, Proia DA, Blackman RK et al. Ganetespib, a unique triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy. Mol Cancer Ther 2012; 11: 475–484.

    Article  CAS  PubMed  Google Scholar 

  17. Mimnaugh EG, Chavany C, Neckers L . Polyubiquitination and proteasomal degradation of the p185c-erbB-2 receptor protein-tyrosine kinase induced by geldanamycin. J Biol Chem 1996; 271: 22796–22801.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Divya Chakravarthy, Jennifer Rebels and Thomas Andrews for technical assistance. We also thank Dr Zhi-Min Yuan for valuable advice and suggestions. This work was supported by the Castella Endowment for Aging Research; Cancer Center Support Grant from the National Cancer Institute (CA054174); National Institutes of Health (HD057118 to M. R.); and Hyundai Hope on Wheel research grant (to GE Tomlinson).

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Authors and Affiliations

  1. Greehey Children’s Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX, USA

    H Bansal, S Ganapathy, L O Penalva, U Suresh, G E Tomlinson, M K Rao & S Bansal

  2. Department of Leukemia & Department of Stem Cell Transplantation and Cellular Therapy, The MD Anderson Cancer Center, Houston, TX, USA

    Q Yihua & S M Kornblau

  3. Methodist Cancer Center, Houston, TX, USA

    S P Iyer

  4. Synta Pharmaceuticals Corp, Lexington, MA, USA

    D Proia

  5. Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, TX, USA

    L O Penalva & M K Rao

  6. Division of Biological Sciences at University of Southern California, Los Angeles, CA, USA

    P J Uren

  7. Department of Medicine, The University of Texas Health Science Center, San Antonio, TX, USA

    A B Karnad

  8. Institute for Drug Development, Cancer Therapy and Research Center, The University of Texas Health Science Center, San Antonio, TX, USA

    J S Carew & S Weitman

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  1. H Bansal
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Correspondence to S Bansal.

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Competing interests

David Proia is an employee and shareholder of Synta Pharmaceuticals Corp. The remaining authors declare no conflict of interest.

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Bansal, H., Yihua, Q., Iyer, S. et al. WTAP is a novel oncogenic protein in acute myeloid leukemia. Leukemia 28, 1171–1174 (2014). https://doi.org/10.1038/leu.2014.16

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