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    Home > Biochemistry News > Biotechnology News > Eliminate cancer cells by changing their identity

    Eliminate cancer cells by changing their identity

    • Last Update: 2021-12-29
    • Source: Internet
    • Author: User
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    In the late 1980s, scientists developed a new method for the treatment of acute myeloid leukemia (AML), which is a type of blood cancer


    Unfortunately, this treatment is only effective for a small number of patients with a specific subtype called acute promyelocytic leukemia (APL)


    Now, Blanco and his colleagues have discovered a new way to trigger the differentiation of AML-one and potentially treat a wider range of AML patients, according to the team published their research (“KAT6A ENL forms an epigenetic transcription control module Drive the key gene expression program that causes leukemia") in the discovery of cancer


    Their research identified an enzyme that regulates the differentiation process of AML cells


    "The epigenetic program is dysregulated in acute myeloid leukemia (AML) and helps perform the oncogenic state of differentiation arrest


    The screening found that histone acetyltransferase KAT6A is a new myeloid cell differentiation regulator, which drives the key leukemia gene expression program


    "Inhibition of KAT6A has a strong anti-AML phenotype in vivo and in vitro, which indicates that KAT6A small molecule inhibitors may have high therapeutic value in single or combined differentiation treatment of AML


    "Acute myeloid leukemia usually has a poor prognosis, with a five-year survival rate of less than 50%," said Blanco, one of the senior corresponding authors of the study


    Looking for candidates

    All cells come from stem cells and reach their final destiny through different differentiation pathways


    Blanco continued: "From an epigenetic point of view, except for rare mutations, every cell in the genome has the same DNA but has completely different functions, which shocked me



    Acute myeloid leukemia (AML) is a blood cancer


    One of the proteins that have been screened to affect cell differentiation is KAT6A, an enzyme called histone acetyltransferase, which modifies DNA and helps epigenetically activate gene expression


    To further understand the activity of KAT6A, the researchers eliminated KAT6A from the human AML cell line and found that the cells grew more slowly


    In order to understand the role of KAT6A in animals, the researchers blocked KAT6A in AML cell lines and then transferred it to immunodeficient mice


    Recognition mechanism

    Now convinced that KAT6A supports the growth of AML by blocking differentiation, Blanco and his team aim to determine the steps it takes and other molecules that interact with it to accomplish this task


    After searching a database containing a lot of information, they found a protein called ENL, which binds together after H3K9ac undergoes an acetyl modification, and this modification is catalyzed by KAT6A
    .
    "It was definitely'Aha! When we searched this database," Blanco said
    .

    This finding helped researchers understand that KAT6A is the so-called "author", which "writes" the modifications of H3K9ac, and ENL is the "reader", absorbs these modifications and operates on them
    .
    Blanco said: "KAT6A prepares for ENL
    .
    "

    With a new understanding of the regulation of AML differentiation, the research team hopes to continue to inhibit KAT6A experiments to see if they can create a new differentiation therapy that can treat more types of AML patients
    .


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