IRIC - Institute for Research in Immunology and Cancer

Published on July 15, 2026

The team led by Guy Sauvageau, director of IRIC’s Molecular Genetics of Stem Cells Research Unit, has identified a subtype of acute myeloid leukemia (AML) characterized by a significant reduction in the cells’ ability to produce proteins resulting from the loss of several ribosomal genes. This study, which proposes a new conceptual model of leukemogenesis, paves the way for the identification of new biomarkers and a new therapeutic vulnerability. Led by Principal Research Advisor Jean-François Spinella, this work is published in the journal Science Advances.

Ribosomal dysfunction characterizes a subgroup of AML

Acute myeloid leukemias are associated with numerous genetic mutations and chromosomal abnormalities. AMLs carrying mutations in the TP53 gene are among the most aggressive and difficult to treat. To better understand their biology, the Sauvageau laboratory analyzed the genomic and transcriptomic profiles of 656 people with AML.

The researchers identified a subgroup of TP53-mutated AML cases exhibiting recurrent losses of several ribosomal genes, particularly on chromosomes 3p and 5q. These alterations lead to a coordinated decrease in the expression of ribosomal genes and an overall reduction in protein synthesis in leukemic cells. The study also shows that these cells become particularly dependent on the activity of the HSP90 chaperone protein, the inhibition of which significantly reduces their proliferation and survival.

A New Understanding of the Disease Paves the Way for Targeted Treatments

The team’s research proposes a new mechanism of leukemogenesis in which ribosomal dysfunction is not merely a consequence of the disease, but a biological driver contributing to its development. They thus suggest that certain cases of AML exhibit a true somatic ribosomopathy, a concept that has received little recognition to date in hematologic cancers.

This discovery allows for the definition of a biologically distinct subgroup of AML, which could be identified using new biomarkers reflecting ribosomal activity, thereby facilitating better patient stratification. Finally, the study highlights a new therapeutic vulnerability by demonstrating that these leukemias are particularly sensitive to HSP90 inhibitors, paving the way for the development of targeted therapeutic approaches.

Cited study

Spinella J-F, Chagraoui J, Boivin I, Richard Carpentier G, Mayotte N, Béliveau F, Lavallée V-P, Hébert J, Sauvageau G. TP53-mutant AML with ribosomal gene loss exhibits impaired protein translation and sensitivity to HSP90 inhibition. Sci. Adv. 12, eaed7122(2026). DOI:10.1126/sciadv.aed7122