Retinoic acid and proteotoxic stress induce AML cell death overcoming stromal cell protection.

ABSTRACT:

Background

Acute myeloid leukemia (AML) patients bearing the ITD mutation in the tyrosine kinase receptor FLT3 (FLT3-ITD) present a poor prognosis and a high risk of relapse. FLT3-ITD is retained in the endoplasmic reticulum (ER) and generates intrinsic proteotoxic stress. We devised a strategy based on proteotoxic stress, generated by the combination of low doses of the differentiating agent retinoic acid (R), the proteasome inhibitor bortezomib (B), and the oxidative stress inducer arsenic trioxide (A).

Methods

We treated FLT3-ITD⁺ AML cells with low doses of the aforementioned drugs, used alone or in combinations and we investigated the induction of ER and oxidative stress. We then performed the same experiments in an in vitro co-culture system of FLT3-ITD

SUBMITTER: Liccardo F 

PROVIDER: S-EPMC10469880 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature