Controlling AML maturation can reduce disease relapse

A promising approach to the treatment of acute myeloid leukaemia (AML) has been discovered by AML researchers at the Australian Centre for Blood Diseases.

Ross Dickins, Stephen Ngo, Ethan Oxley
L-R: A/Prof Ross Dickins, Dr Stephen Ngo and Dr Ethan Oxley are co-authors on the study.

AML is a type of cancer that affects immature progenitor cells (which haven't yet differentiated into a specialised white blood cell type) living in bone marrow.

Some AML therapies cause the immature leukaemia cells to differentiate into mature cells that are cleared away by the body.

In a study published in Nature Communications, the team were able to show that AML cells in mice can mature into multiple mature myeloid lineages, and depending what type they become, will influence disease outcomes. Neutrophils don't contribute to residual disease, being short-lived. Eosinophils live longer and are resistant to therapy.

In the mouse model the team were able to restrict therapy-induced leukemia maturation to the neutrophil lineage, which not only reduced relapse rates but could result in cure.

Their results suggest that differentiation therapies that encourage the progenitor cells to become neutrophils rather than eosinophils, or targeted eradication of therapy-resistant mature AML cells, may improve disease outcome.

Reference

Ngo S, Oxley EP, Ghisi M, Garwood MM, McKenzie MD, Mitchell HL, Kanellakis P, Susanto O, Hickey MJ, Perkins AC, Kile BT, Dickins RA. Acute myeloid leukemia maturation lineage influences residual disease and relapse following differentiation therapy. Nat Commun. 2021 Nov 11;12(1):6546. doi: 10.1038/s41467-021-26849-w. PMID: 34764270; PMCID: PMC8586014.
https://pubmed.ncbi.nlm.nih.gov/34764270/