Ana Rio-Machin

Abstract Identification of specific and therapeutically actionable vulnerabilities, ideally present across multiple mutational backgrounds, is needed to improve acute myeloid leukemia (AML) patients’ outcomes. We identify stearoyl-CoA desaturase (SCD), the key enzyme in fatty acid (FA) desaturation, as prognostic of patients' outcomes and, using the clinical-grade inhibitor SSI-4, show that SCD inhibition (SCDi) is a therapeutic vulnerability across multiple AML models in vitro and in vivo.

In their paper, Gioacchino et al.1 have identified in zebrafish with gata2b haploinsufficiency (an orthologue of GATA2), a compensatory self-regulatory loop to regain normal gata2b levels that results in aberrant myeloid differentiation thus predisposing to myelodysplastic syndrome. This finding provides new insights into the complex regulation of GATA2 expression and how GATA2 haploinsufficiency induces myeloid disease.

Ethics approval Patients gave informed consent for the storage and use of their blood cells for research purposes. Experiments were performed in accordance with the Local Research Ethics Committee, as previously described.16 Primary samples Mononuclear cells from peripheral blood or bone marrow biopsies were isolated in the BCI or FIMM tissue bank facilities and stored in liquid nitrogen.