Role of Autophagy in Differentiation Therapy in AML

Dr Dalyia Benjamin

Dr Benjamin has identified a novel treatment regime, which can lead to the induction of both autophagy and differentiation in cells derived from Acute Myeloid Leukaemia (AML). AML is the most common acute leukemia in adults overall.

The 5-year survival rate of patients under 60 years old is 47% and this drops to 20% for those over 60 years. These figures highlight the urgent need for improved and tolerable therapeutic strategies. In the last two years, we have been collecting primary AML cells so that this novel treatment can be tested on patient cells. This would be a better indication of the likelihood of treatment success in patients. It is hoped that this project will lay the foundations for a new clinical trial of differentiation therapy in AML.

Research Findings

Publications

Benjamin DN, O’Donovan TR, Laursen KB, Orfali N, Cahill MR, Mongan NP, Gudas LJ, McKenna SL. All-Trans-Retinoic Acid Combined With Valproic Acid Can Promote Differentiation in Myeloid Leukemia Cells by an Autophagy Dependent Mechanism. Front Oncol. 2022 Feb 24;12:848517. doi: 10.3389/fonc.2022.848517. PMID: 35280824; PMCID: PMC8907478.

Orfali N, O’Donovan TR, Cahill MR, Benjamin D, Nanus DM, McKenna SL, Gudas LJ, Mongan NP. All-trans retinoic acid (ATRA)-induced TFEB expression is required for myeloid differentiation in acute promyelocytic leukemia (APL). Eur J Haematol. 2020 Mar;104(3):236-250. doi: 10.1111/ejh.13367. Epub 2020 Jan 13. PMID: 31811682.

Orfali N, Jeyapalan JN, Woodcock CL, O’Donovan TR, Benjamin D, Cahill M, McKenna S, Gudas LJ, Mongan NP. Lentiviral-Mediated shRNA Approaches: Applications in Cellular Differentiation and Autophagy. Methods Mol Biol. 2019;2019:33-49. doi: 10.1007/978-1-4939-9585-1_3. PMID: 31359387.