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Investigation of deregulated genes of Notch signaling pathway in human T cell acute lymphoblastic leukemia cell lines and clinical samples

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Abstract

In diagnostic research challenges, quantitative real-time PCR (QPCR) has been widely utilized in gene expression analysis because of its sensitivity, accuracy, reproducibility, and most importantly, quantitativeness. Real-time PCR base kits are wildly applicable in cancer signaling pathways, especially in cancer investigations. T-cell acute lymphoblastic leukemia (T-ALL) is a type of leukemia that is more common in older children and teenagers. Deregulation of the Notch signaling pathway promotes proliferation and inhibits apoptosis of the lymphoblastic T cells. The aim of this study was to investigate the effect of Notch signaling activation on the expression of target genes using real-time QPCR and further use this method in clinical examination after validation. Two T-ALL cell lines, Jurkat and Molt-4, were used as models for activation of the Notch signaling via over-expression of the Notch1 intracellular domain. Expression analysis was performed for six downstream target genes (NCSTN, APH1, PSEN1, ADAM17, NOTCH1 and C-MYC) which play critical roles in the Notch signaling pathway. The results showed significant difference in the expression of target genes in the deregulated Notch signaling pathway. These results were also verified in 12 clinical samples bearing over-expression of the Notch signaling pathway. Identification of such downstream Notch target genes, which have not been studied inclusively, provides insights into the mechanisms of the Notch function in T cell leukemia, and may help identify novel diagnoses and therapeutic targets in acute lymphoblastic leukemia.

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Acknowledgments:

This work was founded by Pasteur Institute of Iran, Tehran. The authors appreciate Stem Cell Technology Research Center, Iran, Tehran, for providing technical support. The authors thank Zahra Masoumi and Lida Langroudi for kindly edition of the manuscript.

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Authors and Affiliations

  1. Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, P.O.Box 1316943551, Tehran, Iran

    Mahdi Paryan, Samira Mohammadi-Yeganeh, Morteza Karimipoor & Reza Mahdian

  2. Food and Drug Laboratory Research Center, Ministry of Health and Medical Education, Tehran, Iran

    Siamak Mirab Samiee

  3. Department of Hematology, Tarbiat Modares University, Tehran, Iran

    Masoud Soleimani

  4. Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran

    Samira Mohammadi-Yeganeh, Masoud Soleimani & Ehsan Arefian

  5. Department of Virology, Pasteur Institute of Iran, Tehran, Iran

    Keyhan Azadmanesh

  6. Islamic Azad University, Tehran Medical Branch, Tehran, Iran

    Behzad Poopak

  7. Department of Epidemiology, Pasteur Institute of Iran, Tehran, Iran

    Ehsan Mostafavi

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  1. Mahdi Paryan
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  2. Samira Mohammadi-Yeganeh
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  3. Siamak Mirab Samiee
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  9. Morteza Karimipoor
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  10. Reza Mahdian
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Correspondence to Morteza Karimipoor or Reza Mahdian.

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Paryan, M., Mohammadi-Yeganeh, S., Samiee, S.M. et al. Investigation of deregulated genes of Notch signaling pathway in human T cell acute lymphoblastic leukemia cell lines and clinical samples. Mol Biol Rep 40, 5531–5540 (2013). https://doi.org/10.1007/s11033-013-2654-8

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  • DOI: https://doi.org/10.1007/s11033-013-2654-8

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