IRIC - Institute for Research in Immunology and Cancer

Published on June 25, 2024

Immunotherapies, which are more natural and less toxic than chemotherapies, have made major advances in recent years. However, they remain relatively unexploited in the treatment of acute myeloid leukemia (AML), a type of leukemia that is particularly heterogeneous genetically and difficult to treat. The Leucegene group, led by Guy Sauvageau (IRIC’s Molecular Genetics of Stem Cells Research Unit) and Josée Hébert (Centre de recherche de l’Hôpital Maisonneuve-Rosemont), and involving the teams of Philippe Roux, Sébastien Lemieux and Pierre Thibault at IRIC, and of Vincent-Philippe Lavallée at the CHU Ste-Justine Research Centre, has developed a new approach to analyze the molecules present on the surface of leukemia cells. Their work has led to the identification, in AML specimens, of new high-potential targets for immunotherapies. The study was led by Marie-Ève Bordeleau, Deputy Director of the Sauvageau laboratory, and is published in the journal Cell Reports.

Finding answers on the cell surface

To identify new ways of targeting AMLs, the Leucegene group has developed a powerful approach to analyze all the proteins present on the surface of leukemia cells. The team analyzed 100 genetically distinct human AML specimens, representing the largest dataset of this type analyzed to date. By cross-referencing these data with RNA sequencing results, the group built the Leucegene AML Surfaceome Atlas (LASA), a bioinformatics tool made freely available to the entire scientific community.

A therapeutic potential to exploit

Using this approach, the team was able to identify antigens (proteins that can be recognized by the immune system) and markers specific to distinct subpopulations of AML cells.

Some of the antigens identified are the target of existing therapeutic antibodies already under clinical evaluation for other diseases; these antibodies could be “repurposed” and tested in an AML context. Other antigens, meanwhile, have a favorable safety profile for clinical use; as they are not presented by healthy cells, it could be interesting to develop therapeutic antibodies targeting them.

In short, the study paves the way for the exploitation of immunotherapeutic strategies to overcome the great genetic variability of AMLs and help improve prognosis for patients.

Cited study

Bordeleau M-E, Audemard É, Métois A, Theret L, Lisi V, Farah A, Spinella J-F, Chagraoui J, Moujaber O, Aubert L, Khakipoor B, Mallinger L, Boivin I, Mayotte N, Hajmirza, Bonneil, É, Béliveau F, Pfammatter S, Feghaly A, Boucher G, Gendron P, Thibault P, Barabé F, Lemieux S, Richard-Carpentier G, Hébert J, Lavallée V-P, Roux P.P, Sauvageau G. Immunotherapeutic targeting of surfaceome heterogeneity in AML. Cell Reports, 2024. https://doi.org/10.1016/j.celrep.2024.114260