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Acute myeloid leukaemia (AML) is an aggressive blood cancer, for which most patients are not eligible for intensive chemotherapy or stem cell transplantation. Therefore, less toxic and more efficient targeted therapies are urgently needed.
A recent clinical trial for AML patients with IDH1 mutations tested the effectiveness of a drug combination of ivosidenib and venetoclax (with or without azacitidine). Although most patients responded well, several developed resistance to treatment and relapsed. To understand why, the Vyas Group in Oxford worked with collaborators at the MD Anderson Cancer Center in Houston to study bone marrow samples from patients before, during, and after treatment.
The researchers used a powerful single cell technique, called TARGET-seq+, to track cancer clones in patient samples. They discovered that drug-resistant cancer cells were selected very quickly – within one to three treatment cycles – even while patients were still in remission. This occurred in all analysed patients who relapsed, whether relapse occurred within months or even years of treatment.
These resistant clones came from small populations of immature cells known to have “stem cell–like” properties. Meanwhile, most of the cells in the bone marrow remained clear of relapse-associated mutations and blood production was sustained by normal cells, masking the hidden resistant clones. In contrast, patients who stayed in long-term remission showed complete or near-complete removal of all leukaemic cells.
Read the full story on the Radcliffe Department of Medicine website.