Background: While progress continues in the understanding of molecular abnormalities in acute myeloid leukaemia (AML), with some specific targeted therapies now available, it remains commonly fatal in the elderly. Leukaemic evolution and transformation from myeloproliferative neoplasms (MPN) may be associated with increased numbers of mutations in the genes associated with myeloid neoplasm and the prognosis in such patients is invariably dismal. Targeting of intracellular enzymes associated with integral cellular function has advanced understanding and promises improvements in treatments. Case: We report impressive prolonged response to therapy in a case of secondary AML, arising from essential thrombocythaemia (ET). The trial agent, the oral lysine-specific histone demethylase 1 (LSD1) inhibitor Bomedemstat (IMG-7289) was well tolerated. In addition to suppressing the malignant clone, these blasts showed differentiation to monocytes morphologically as well as by surface markers seen on flow cytometry. Bomedemstat has efficacy in the treatment of myelofibrosis and may have a special role in treatment of specific AML subtypes, including secondary leukaemias arising from MPN as seen. Conclusion: We report a case of an older adult with secondary AML transformed from ET, with a remarkable response to LSD1 inhibition with Bomedemstat, with prolonged reduction in blasts demonstrating differentiation to monocytes.