Researchers have shed light on the drug sensitivities of rare subtypes of acute myeloid leukaemia (AML). A team led by scientists from the University of Helsinki found that erythroid and megakaryoblastic leukaemias are resistant to the new drug venetoclax, but inhibitors of BCL-XL could be effective against these forms of disease.
The laboratory study, published in Blood, involved the screening of more than 500 potential drugs that could be effective against cell lines of erythroid and megakaryoblastic leukaemias. Further studies testing the drugs on samples from patients, and in mice, confirmed the effectiveness of BCL-XL inhibitors.
The team also found these rare subtypes were resistant to venetoclax – which targets the BCL-2 protein – contrasting with their effectiveness in other AML subtypes.
Professor Satu Mustjoki, professor of translational haematology at the University of Helsinki, said: “This finding may in the future improve the prognosis of these very rare and difficult-to-treat leukaemias.”
Researcher Dr Heikki Kuusanmäki said: “The laboratory findings provide evidence that patients with erythroid or megakaryoblastic acute leukaemia would be a promising group for investigating the efficacy of BCL-XL inhibitors in clinical use.”
Kuusanmäki H, Kytölä S, Vänttinen I, Ruokoranta T, Ranta A, Huuhtanen J, Suvela M, Parsons A, Holopainen A, Partanen A, Kuusisto MEL, Koskela S, Räty R, Itälä-Remes M, Västrik I, Dufva O, Siitonen S, Porkka K, Wennerberg K, Heckman CA, Ettala P, Pyörälä M, Rimpiläinen J, Siitonen T, Kontro M. (2022) “Erythroid/megakaryocytic differentiation confers BCL-XL dependency and venetoclax resistance in acute myeloid leukemia.” Blood, doi:blood.2021011094
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