• Novel acute myeloid leukemia subtypes id

    From ScienceDaily@1:317/3 to All on Mon Mar 7 21:30:46 2022
    Novel acute myeloid leukemia subtypes identified

    Date:
    March 7, 2022
    Source:
    Max-Planck-Gesellschaft
    Summary:
    Researchers have discovered the first proteomic subtype of an
    aggressive blood cancer by using mass spectrometry technology.



    FULL STORY ==========================================================================
    In order to better treat patients diagnosed with acute myeloid leukemia
    (AML), researchers need to understand the pathological processes and distinguish between different subgroups of the disease. With the help of proteome and genetic analysis, researchers at the Max Planck Institute
    of Biochemistry in Martinsried, together with cooperation partners
    from the Frankfurt University Hospital, German Cancer Research Center
    (DKFZ) as well as German Cancer Consortium (DKTK) have discovered a new subtype. This subtype shows increased amounts of mitochondrial proteins
    as well as an altered mitochondrial metabolism. In laboratory tests,
    these so-called Mito-AML cells can be combated more effectively with
    inhibitors against mitochondrial respiration than with conventional chemotherapeutic agents.


    ========================================================================== Acute myeloid leukemia (AML) is an aggressive cancer originating from
    blood cells. When immature blood cells in the bone marrow acquire certain aberrations in their genome they can become malignant and overgrow the
    bone marrow, the place where normally blood cells are produced. As a consequence, normal blood cells are suppressed by leukemia cells which
    leads to infections, bleeding and ultimatively death of patients. Most
    patients diagnosed with AML undergo chemotherapy.

    In a multidisciplinary project, a team of researchers led by Matthias
    Mann from the Max Planck Institute of Biochemistry as well as Thomas
    Oellerich and Hubert Serve from the University Hospital Frankfurt, DKTK &
    DKFZ studied the proteome -- i.e. the totality of all proteins -- of AML
    cells. By combining the proteome and genome data, the researchers have identified several AML subgroups with specific biological features. One
    of the subgroups -- the so-called Mito-AML - - was only recognisable at
    the proteome level and had therefore not been discovered before. The new subgroup is characterised by a high number of mitochondrial proteins
    and an altered mitochondrial metabolism and shows clinical resistance
    to chemotherapy.

    Possible approach for new therapies Since mitochondria are the power
    plants of cells, the research team further investigated whether the disease-specific metabolic changes in Mito-AML can be therapeutically exploited. In a series of experiments, they found that drugs that
    interfere with mitochondrial respiration are highly effective in Mito-AML
    cell cultures and thus might be a more effective therapy compared to traditional chemotherapeutics. These agents include, for example, the
    drug venetoclax.

    In the last decades genomic studies already identified molecular
    subtypes within the disease thereby opening up a perspective for
    personalized therapeutic approaches. This has certainly revolutionised
    the molecular understanding of the disease and laid the groundwork for personalised therapies. Despite these developments, the prognosis for
    AML remains poor. This highlights the urgent need to better understand
    the pathologically altered processes during AML and to search for more efficient therapies.

    To study the protein expression profiles in AML cells, the team used
    mass spectrometry. This technology allows proteins to be identified and quantified by determining their specific weight. The protein expression profiles provide researchers with an overview of which proteins are
    present in the pathologically altered cells and in what quantities. In parallel, the team examined the human genome of AML cells using DNA and
    RNA sequencing technologies.

    "The discovery of the Mito-AML subset demonstrates the great potential
    of proteomics technology for identifying clinically relevant biomarkers
    and drug targets. Our study clearly shows that genomic and proteomic data complement each other, allowing us to elucidate previously undescribed
    aspects of disease biology and to name innovative treatment approaches,"
    says Matthias Mann. "Our approach led to the discovery of new molecular
    AML subgroups with clinical relevance. It thus provides a proteomic
    systematics as a basis for a better molecular understanding and clinical classification of AML," says Thomas Oellerich.

    This new insight was made possible through close collaboration between clinicians at Frankfurt University and the Study Alliance Leukemia
    (SAL), a nationwide network to improve the treatment of AML, and basic scientists. "It helps us understand why some patients respond better
    to different forms of therapy than others," says Hubert Serve. Next,
    medical researchers want to test the laboratory results in clinical
    trials on patients.

    ========================================================================== Story Source: Materials provided by Max-Planck-Gesellschaft. Note:
    Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Ashok Kumar Jayavelu, Sebastian Wolf, Florian Buettner, Gabriela
    Alexe,
    Bjo"rn Ha"upl, Federico Comoglio, Constanze Schneider, Carmen
    Doebele, Dominik C. Fuhrmann, Sebastian Wagner, Elisa Donato,
    Carolin Andresen, Anne C. Wilke, Alena Zindel, Dominique Jahn,
    Bianca Splettstoesser, Uwe Plessmann, Silvia Mu"nch, Khali
    Abou-El-Ardat, Philipp Makowka, Fabian Acker, Julius C. Enssle,
    Anjali Cremer, Frank Schnu"tgen, Nina Kurrle, Bjo"rn Chapuy,
    Jens Lo"ber, Sylvia Hartmann, Peter J. Wild, Ilka Wittig,
    Daniel Hu"bschmann, Lars Kaderali, Ju"rgen Cox, Bernhard Bru"ne,
    Christoph Ro"llig, Christian Thiede, Bjo"rn Steffen, Martin
    Bornha"user, Andreas Trumpp, Henning Urlaub, Kimberly Stegmaier,
    Hubert Serve, Matthias Mann, Thomas Oellerich. The proteogenomic
    subtypes of acute myeloid leukemia. Cancer Cell, 2022; DOI:
    10.1016/j.ccell.2022.02.006 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220307113104.htm

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