Open Access

High expression of FLT3 is a risk factor in leukemia

  • Authors:
    • Jie Cheng
    • Lijun Qu
    • Jian Wang
    • Lemei Cheng
    • Yi Wang
  • View Affiliations

  • Published online on: December 8, 2017     https://doi.org/10.3892/mmr.2017.8232
  • Pages: 2885-2892
  • Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Several studies have shown that internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3) can result in the failure of leukemia treatment and contribute to a poor prognosis. However, the role of the overexpression of FLT3 in leukemia remains to be fully elucidated. By mining public database, the present study first identified that the expression of FLT3 in leukemia was markedly higher, compared with that in other types of tumor and cell lines, indicating that FLT3 is important in leukemia. In leukemia, FLT3 was found to be significantly upregulated in acute myeloid leukemia and acute lymphoblastic leukemia, and a high expression of FLT3 contributed to reduced survival rates. By analyzing Gene Expression Omnibus and The Cancer Genome Atlas data, it was found that genetic alterations and modification of DNA methylation increased the expression of FLT3 in leukemia. FLT3‑ITD and FLT3 tyrosine kinase domain point mutations increased the expression of FLT3 in four independent datasets. In addition, the status of FLT3 gene methylation was negatively correlated with the expression of FLT3, and haploinsufficiency of DNA methyltransferase 1 increased the expression of Flt3 in mouse leukemia cells. By analyzing the enrichment of differentially‑expressed genes in chemical and genetic perturbation datasets, it was found that genes, which were upregulated in the FLT3 high expression group had myeloid lymphoid leukemia‑ and nucleophosmin 1‑like signatures, indicating that the overexpression of FLT3 may use the same mechanism to promote leukemia. Collectively, the results of the present study showed that the overexpression of FLT3 is a potential risk factor in leukemia.
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February-2018
Volume 17 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Cheng J, Qu L, Wang J, Cheng L and Wang Y: High expression of FLT3 is a risk factor in leukemia. Mol Med Rep 17: 2885-2892, 2018.
APA
Cheng, J., Qu, L., Wang, J., Cheng, L., & Wang, Y. (2018). High expression of FLT3 is a risk factor in leukemia. Molecular Medicine Reports, 17, 2885-2892. https://doi.org/10.3892/mmr.2017.8232
MLA
Cheng, J., Qu, L., Wang, J., Cheng, L., Wang, Y."High expression of FLT3 is a risk factor in leukemia". Molecular Medicine Reports 17.2 (2018): 2885-2892.
Chicago
Cheng, J., Qu, L., Wang, J., Cheng, L., Wang, Y."High expression of FLT3 is a risk factor in leukemia". Molecular Medicine Reports 17, no. 2 (2018): 2885-2892. https://doi.org/10.3892/mmr.2017.8232