title: Investigation of deregulated genes of Notch signaling pathway in human T cell acute lymphoblastic leukemia cell lines and clinical samples.
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.
authors: Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, P.O.Box 1316943551, Tehran, Iran.
authors: Mahdi
authors: M
authors: Paryan
authors: Samira
authors: S
authors: Mohammadi-Yeganeh
authors: Siamak Mirab
authors: SM
authors: Samiee
authors: Masoud
authors: M
authors: Soleimani
authors: Ehsan
authors: E
authors: Arefian
authors: Keyhan
authors: K
authors: Azadmanesh
authors: Behzad
authors: B
authors: Poopak
authors: Ehsan
authors: E
authors: Mostafavi
authors: Morteza
authors: M
authors: Karimipoor
authors: Reza
authors: R
authors: Mahdian
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002648:Child; D005260:Female; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D052138:Genes, Neoplasm / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*; D012015:Reference Standards; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics*; D014161:Transduction, Genetic
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051880:Receptors, Notch
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