A new target to fight certain aggressive leukaemias

Researchers from the Toulouse Cancer Research Centre and the Centre for Translational Research in Onco-Haematology of the Faculty of Medicine of the University of Geneva have teamed up to investigate a new therapeutic approach for acute myeloid leukaemia (AML). To read in Cancer Discovery.

© Jérôme Tamburini / UNIGE.  LAM  cells (in purple)

AML is a type of cancer that affects the blood and is characterized by uncontrolled proliferation of certain initiating cells of the immune system. AML disrupts the physiological process of blood cell production, leading to severe symptoms, and up to 60% of cases are fatal.

 The researchers focused on mutations in the FLT3 gene, which are associated with poor prognosis and frequent relapse after chemotherapy. They investigated the C/AAT-enhancer binding protein α (C/EBPα), a protein known to be a key transcription factor in myeloid cell differentiation. In a study published in the journal Cancer Discovery, the scientists found that coordinated activation of C/EBPα and FLT3 increases the production of certain monounsaturated fatty acids in FLT3-mutated AML cells, particularly via expression of the enzyme Stearoyl-CoA-Desaturase (SCD).

 In addition, the research team found that inhibition of the FLT3 gene causes metabolic changes in response to down-regulation of C/EBPα-SCD, which induces oxidation of cell membrane lipids and thus succeeds in killing leukaemia cells. This discovery identifies a potential therapeutic target and opens the prospect of a novel therapeutic strategy based on the use of molecules capable of inducing cell death through the accumulation of toxic oxidized lipids in AML cells.

4 Apr 2023