TP53-mutant AML with ribosomal gene loss exhibits impaired protein translation and sensitivity to HSP90 inhibition - PubMed
3 days ago
- #TP53-mutant AML
- #HSP90 inhibition
- #Ribosomal gene loss
- TP53-mutated AML is an aggressive, therapy-resistant subtype, with recurrent chromosomal abnormalities like -5/del(5q), -7/del(7q), and del(17p).
- A distinct subset of TP53-altered AML features del(3p), often co-occurring with del(5q), leading to loss of ribosomal protein genes (RPGs) and reduced protein synthesis.
- This ribosomopathy-like phenotype is most severe in cases with combined RPG deletions on chromosomes 3p and 5q, indicating cooperative oncogenic effects.
- HSP90 inhibition was identified as a selective vulnerability in AML with low RPG expression, suggesting ribosomal stress as a therapeutic target.