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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