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    Home > Active Ingredient News > Antitumor Therapy > Blood: New demethylation drug OR-2100 targets treatment of DNA abnormal supermethylation-driven ATL leukemia

    Blood: New demethylation drug OR-2100 targets treatment of DNA abnormal supermethylation-driven ATL leukemia

    • Last Update: 2020-06-16
    • Source: Internet
    • Author: User
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    Adult T-cell leukemia - lymphoma (ATL) is an invasive CD4-T cell blood tumor transformed by human T-cell lymphatic virus-1 (HTLV-1)Most individuals infected with HTLV-1 are asymptomatic, and only 3-5% of HTLV-1 carriers develop ATLIn this study, the researchers outlined the contribution of DNA methylation to the onset of ATL leukemiaAccording to the expression status of CADM1 and CD7, T cells infected with HTLV-1 can be isolated and uninfected T cells separately, and the differential methylation location (DMPs) of T-cell specificity of HTLV-1 infection is identified through the whole genome DNA methylation spectrumThe accumulation of DNA methylation at supermethylated DMPs is closely related to the development of ATLIn addition, the researchers found 22 genes that were lowered by promoter hypermethylation in T cells infected with HTLV-1, including THEMIS, LAIR1, and RNF130, which are negatively regulated T-cell receptor (TCR) signalsIn the cell line of HTLV-1 infection, the phosphorylation of the TCR signal transponder ZAP-70 is abnormal, but the phosphorylation of ZAP-70 can be normalized by REexpression by THEMISAs a result, the researchers speculated that DNA hypermethylation could contribute to the growth advantage of HTLV-1 infected cells during the ongoing at-ATL leukemiaTo test this hypothesis, Watanabe et alstudied the anti-ATL activity of the new geo-sitabin OR-1200 and OR-2100 (OR21) to enhance oral bioavailabilityIn hCHLV-1 infected cell implanted xenotransplantous tumors, both DAC and OR21 inhibit cell growth and are accompanied by low methylation of overall DNAOR21 has less hemotoxicity than DAC, and the tumor growth inhibition of both compounds is almost identical, making them suitable for long-term treatment of ATL patient-derived xenotransplantmice miceIn summary, the results of this study show that regional DNA supermethylation has an important function in the occurrence of ATL leukemia and can be used as an effective target for treatment
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