Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models.

ABSTRACT:

Purpose

To characterize the prevalence of hypoxia in the leukemic bone marrow, its association with metabolic and transcriptional changes in the leukemic blasts and the utility of hypoxia-activated prodrug TH-302 in leukemia models.

Experimental design

Hyperpolarized magnetic resonance spectroscopy was utilized to interrogate the pyruvate metabolism of the bone marrow in the murine acute myeloid leukemia (AML) model. Nanostring technology was used to evaluate a gene set defining a hypoxia signature in leukemic blasts and normal donors. The efficacy of the hypoxia-activated prodrug TH-302 was examined in the in vitro and in vivo leukemia models.

Results

Metabolic imaging has demonstrated increased glycolysis in the femur of leukemic mice compared with healthy control m

SUBMITTER: Benito J 

PROVIDER: S-EPMC4818660 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature