News in brief: Combination therapy may overcome resistant AML; Stonefish venom causes anticoagulation; Lifeblood rethink on UK blood donor ban

New combination may overcome AML resistance

Researchers at the Walter and Eliza Hall Institute (WEHI) have discovered why some leukaemia cells are resistant to new ‘SMAC-mimetic’ anti-cancer agents such as birinapant, a finding that could lead to combination therapy that would overcome drug resistance.

The team showed that the ‘drug pump’ protein MDR1 makes acute myeloid leukaemia (AML) cells resistant to SMAC-mimetics by rapidly pumping out the drug of the cells before it can work. Their work published in Blood Advances, also showed that treating AML cells with inhibitors of MDR1 allowed the SMAC-mimetics to accumulate and kill the leukaemia cells.

“This suggests that MDR1 inhibitors could potentially be combined with SMAC-mimetics to create an effective new combination treatment,” said study investigator Dr Gabriela Brumatti.

She added that the combination could also kill leukaemia ‘stem cells’, which were thought to be a source of cancer recurrence.

Stonefish venom has anticoagulant toxicity

A new investigation into the excruciatingly painful venom of Australia’s reef stonefish has found that it also causes anticoagulation in addition to its neurotoxic and cardiotoxic actions. Researchers at Queensland University’s Venom Evolution Laboratory, tested stonefish venom on a thromboelastography assay and found that it showed significant anticoagulant activity and significantly delayed time until clot formation with human plasma. The toxins within S. verrucosa venom were likely acting on either the extrinsic pathway or interfering with coagulation cofactors such as phospholipids, said the researchers after finding no inhibitory effect on the intrinsic pathway; thrombin, FXa, prothrombinase complex, FIXa and FXIa. The degradation and hydrolysis of phospholipids was a known anticoagulant mechanism from phospholipase class toxins in other fish venoms, they said.

Toxicology Letters

Lifeblood rethink on UK blood donor ban

Australian Red Cross Lifeblood is reconsidering its ban on accepting blood donations from people who spent more than six months in the UK between 1980 and 1996, who may have been exposed to variant Creutzfeldt-Jakob disease (vCJD).  According to media reports, Lifeblood is reviewing the medical evidence on  prion disease transmission  and risk blood supply and will preparing a submission to regulators on wait time changes for those who lived in or visited the UK during the vCJD risk period. The ban was introduced after a number of people in the UK contracted vCJD from blood transfusions at the height of the outbreak, thought to be due to bovine spongiform encephalopathy (BSE,  ‘mad cow disease’) in the 1990s.

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