Inducible transgene expression in PDX models in vivo identifies KLF4 as a therapeutic target for B-ALL.

ABSTRACT:

Background

Clinically relevant methods are not available that prioritize and validate potential therapeutic targets for individual tumors, from the vast amount of tumor descriptive expression data.

Methods

We established inducible transgene expression in clinically relevant patient-derived xenograft (PDX) models in vivo to fill this gap.

Results

With this technique at hand, we analyzed the role of the transcription factor Krüppel-like factor 4 (KLF4) in B-cell acute lymphoblastic leukemia (B-ALL) PDX models at different disease stages. In competitive preclinical in vivo trials, we found that re-expression of wild type KLF4 reduced the leukemia load in PDX models of B-ALL, with the strongest effects being observed after conventional chemotherapy in minimal residual dis

SUBMITTER: Liu WH 

PROVIDER: S-EPMC7493381 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature