Infliximab therapy together with tyrosine kinase inhibition targets leukemic stem cells in chronic myeloid leukemia.

ABSTRACT:

Background

Expression of Bcr-Abl in hematopoietic stem cells is sufficient to cause chronic myeloid leukemia (CML) and tyrosine kinase inhibitors (TKI) induce molecular remission in the majority of CML patients. However, the disease driving stem cell population is not fully targeted by TKI therapy, and leukemic stem cells (LSC) capable of re-inducing the disease can persist. Single-cell RNA-sequencing technology recently identified an enriched inflammatory gene signature with TNFα and TGFβ being activated in TKI persisting quiescent LSC. Here, we studied the effects of human TNFα antibody infliximab (IFX), which has been shown to induce anti-inflammatory effects in mice, combined with TKI treatment on LSC function.

Methods

We first performed GSEA-pathway analysis using our m

SUBMITTER: Herrmann O 

PROVIDER: S-EPMC6610865 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature