Chemoresistance of TP53 mutant acute myeloid leukemia requires the mevalonate byproduct, geranylgeranyl pyrophosphate, for induction of an adaptive stress response.

doi:10.1038/s41375-025-02668-6

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Chemoresistance of TP53 mutant acute myeloid leukemia requires the mevalonate byproduct, geranylgeranyl pyrophosphate, for induction of an adaptive stress response.

Leukemia - 1 Sept 2025

Skuli Sarah J, Bakayoko A'ishah, Kruidenier Marisa, Manning Bryan, Pammer Paige, Salimov Akmal, Riley Owen, Brake-Sillá Gisela, Dopkin Derrick, Bowman Michael, Martinez-Gutierrez Leslie N, Anderson Colin C, Reisz Julie A, Buono Roberta, Paul Madhuri, Saland Estelle, Liccardo Francesca, DeVine Ann, Wong Sarah, Xu Jimmy P, Nee Eva, Hausler Ryan, Boettcher Steffen, Sebti Said M, Lai Catherine, Maxwell Kara N, Sarry Jean-Emmanuel, Fruman David A, D'Alessandro Angelo, Mesaros Clementina, Keith Brian, Simon M Celeste, Sung Pamela J, Wertheim Gerald, Skuli Nicolas, Bowman Robert L, Matthews Andrew, Carroll Martin

Abstract excerpt

Acute myeloid leukemia with mutations in TP53 (TP53mut AML) is fatal with a median survival of 6 months. RNA sequencing on purified AML patient samples showed that TP53mut AML had higher expression of mevalonate pathway genes. Using novel, isogenic TP53mut AML cell lines and primary samples, we determined that TP53mut AML resistance to AML chemotherapy cytarabine (AraC) correlated with increased mevalonate...

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Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

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Identifiers

PMID: 40634510
DOI: 10.1038/s41375-025-02668-6
PMCID: PMC12380605

Genes

TP53

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 4 Sept 2026.

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