News in brief: Overcoming venetoclax resistance in AML; 3 ways to reduce carbon footprint from diagnostic imaging; ASCOT ends anticoagulation treatment arm for COVID-19

11 May 2022

Overcoming venetoclax resistance in AML

South Australian scientists have developed a potential method for overcoming venetoclax resistance in acute myeloid leukaemia (AML).

In a study published in the journal Blood, researchers from the University of South Australia and SA Pathology’s Centre for Cancer Biology describe their work showing that enhancing cellular ceramide levels in AML activates protein kinase R to induce the integrated stress response (ISR). They say this inducesd the BH3-only protein Noxa, resulting in degradation of Mcl-1 and sensitisation of AML to Bcl-2 inhibition.

“Targeting this novel ISR pathway in combination with the Bcl-2 inhibitor venetoclax synergistically killed primary AML blasts, including those with venetoclax-resistant mutations, as well as immunophenotypic leukaemic stem cells, and reduced leukemic engraftment in patient-derived AML xenografts,” they reported

“Collectively, these findings provide mechanistic insight into the anti-cancer effects of ceramide and pre-clinical evidence for new approaches to augment Bcl-2 inhibition in the therapy of AML and other cancers with high Mcl-1 dependency.

The 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,” said co-author and SA Pathology haematologist Associate Professor David Ross.

“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.”

3 ways to reduce carbon footprint from diagnostic imaging

Clinicians can help reduce the healthcare carbon footprint by adopting a three-pronged strategy to make more efficient use diagnostic imaging, according to Australian researchers.

Diagnostic imaging and pathology testing account for almost 10% of the carbon footprint, with MRI and CT scans accounting for a high proportion of it,  a Melbourne University study found.

The carbon emissions from an MRI are equivalent to driving a car for 145km, while a CT scan carbon emission are equal to driving 76 km, the findings in Lancet Regional Health showed.

Much of the large carbon footprint was due to electricity use by scanners, and in particular, their standby power use, said the researchers, who recommended that clinicians and administrators make efforts to reduce unnecessary imaging or by changing imaging to a lower carbon modality.

Other carbon reduction tips include turning scanners off when they are not required rather than leaving them in standby and ensuring existing scanners have high utilisation rates, they suggested.

ASCOT ends anticoagulation treatment arm for COVID-19

The Australasian COVID-19 Trial (ASCOT) Trial Steering Committee has closed the anticoagulation treatment domain of the study that aims to evaluate treatments for patients hospitalised with COVID-19.

Study investigators said the decision to stop enrolments into anticoagulation treatment was based on lower than expected numbers of COVID-19 patients meeting the primary outcome for the ASCOT study.

“We are seeing a much slower recruitment rate with a highly vaccinated population and less severe variant, that is resulting in less people being admitted to hospital for COVID pneumonitis. This means the Anticoagulation Treatment Domain is unlikely to reach a sample size that would meet a statistical trigger in a timely manner,” they said.

The trial has enrolled 1575 participants in the anticoagulation domain worldwide, and investigators plan to report results on the effect of anticoagulation treatment of varying dose for patients with COVID-19 in a final analysis of the ASCOT study.

“We hope the results from this domain will also contribute to meta-analyses and be pooled with other international clinical trials examining the effects of anticoagulation treatment for patients with COVID-19,” the investigators said.

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