• Major discovery provides new hope for bl

    From ScienceDaily@1:317/3 to All on Monday, May 09, 2022 22:30:42
    Major discovery provides new hope for blood cancer patients

    Date:
    May 9, 2022
    Source:
    University of South Australia
    Summary:
    Acute myeloid leukaemia is a rare and devastating blood cancer that
    is highly resistant to treatment. Now, scientists have discovered
    a way to suppress a specific protein that promotes drug resistance.



    FULL STORY ========================================================================== South Australian scientists have made a significant breakthrough in
    overcoming drug resistance in acute myeloid leukemia (AML), a rare and devastating blood cancer that kills most patients within a few years.


    ==========================================================================
    In a new study published in the world-leading hematology journal Blood, researchers from the University of South Australia and SA Pathology's
    Centre for Cancer Biology describe how they have discovered a way to
    suppress a specific protein that promotes resistance to drugs commonly
    used to treat AML patients.

    Professor Stuart Pitson, one of the lead authors of the study, says
    the finding could revolutionise the treatment of AML, a disease that
    has claimed the lives of Australian football great Russell Ebert,
    professional golfer Jarrod Lyle, high-profile American journalist Nora
    Ephron and filmmaker Lynn Shelton.

    This year, it is estimated that 20,000 people in the United States and
    900 people in Australia will be diagnosed with acute myeloid leukemia,
    a cancer of the blood and bone marrow characterised by an overproduction
    of cancerous white blood cells called leukaemic blasts.

    Prof Pitson says these cells crowd out normal white blood cells, which
    then can't do their usual infection-fighting work, thereby increasing
    the risk of infections, low oxygen levels and bleeding.

    SA Pathology haematologist Associate Professor David Ross says many AML patients initially respond to Venetoclax, a new therapy for AML recently
    listed on the PBS, but over time AML cells become resistant to it.



    ========================================================================== Using a large biobank of patient-donated AML biopsies and world-leading advanced pre-clinical models, the CCB researchers demonstrated that
    by modulating lipid metabolism in the body, a protein called Mcl-1 is
    inhibited in AML cells -- the protein that facilitates drug resistance.

    "This process makes AML cells exquisitely sensitive to Venetoclax,
    while leaving the normal white blood cells unaffected," SA Pathology
    researcher and co-lead author, Associate Professor Jason Powell says.

    The CCB team is now working hard to optimise drugs targeting this pathway
    to take into clinical trials for AML patients.

    "For most people with AML, the chances of long-term survival are no
    better now than they were last century," Assoc Prof Ross says.

    "Now, we have a chance to remedy that. New treatments that prevent
    Venetoclax resistance have the potential to prolong survival, or even
    increase the chances of a cure in a disease for which improved outcomes
    are desperately needed." Background


    ========================================================================== Acute myeloid leukemia (AML) accounts for approximately 0.8 per cent of
    all cancers diagnosed, at a rate of 3.7 per 100,000 people. It can occur
    at any age but is more common in adults (and men) over the age of 60.

    In most cases the causes remain unknown, but it is thought to result from damage to one of more genes that normally control blood cell development.

    Current therapies are effective at putting patients into remission, but
    relapse is common, with fewer than 30 per cent of AML patients surviving
    five years post diagnosis.

    In 1990, acute myeloid leukemia (AML) accounted for 18.0% of the total
    leukemia cases worldwide. This proportion increased to 23.1% in 2017.


    ========================================================================== Story Source: Materials provided by University_of_South_Australia. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Alexander C Lewis, Victoria S Pope, Melinda N Tea, Manjun Li, Gus O
    Nwosu, Thao M Nguyen, Craig Thomas Wallington-Beddoe, Paul A
    Moretti, Dovile Anderson, Darren J Creek, Maurizio Costabile,
    Saira R Ali, Chloe AL Thompson-Peach, B Kate Dredge, Andrew G Bert,
    Gregory J Goodall, Paul G Ekert, Anna L Brown, Richard J D'Andrea,
    Nirmal Robinson, Melissa R Pitman, Daniel Thomas, David M Ross,
    Briony L Gliddon, Jason A Powell, Stuart M Pitson. Ceramide-induced
    integrated stress response overcomes Bcl-2 inhibitor resistance in
    acute myeloid leukemia. Blood, 2022; DOI: 10.1182/blood.2021013277 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/05/220509100940.htm

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