Chronic Myeloid Leukemia Coverage from Every Angle

Infliximab Therapy With Tyrosine Kinase Inhibition in CML

By: Hillary Ojeda
Posted: Wednesday, August 14, 2019

According to a study published in the journal BMC Cancer, anti-inflammatory therapy in mice with chronic myeloid leukemia (CML) appears to bring about tyrosine kinase inhibition decline of LSK cells. This approach shows that treatment strategies that focus on myeloid leukemia cells may be improved by targeting their malignant microenvironment. Conducted by Mirle Schemionek, PhD, of the University Hospital RWTH Aachen, Germany, and colleagues, the study results suggest further investigation into the persistence of tyrosine kinase inhibition therapy is needed.

Using a microarray of murine LSK cells (lin−; Sca-1+; c-kit+) from the from the SCLtTA/Bcr-Abl CML transgenic mouse model, the investigators carried out a gene set enrichment analysis–pathway evaluation. Mice with CML received nilotinib or nilotinib plus infliximab.

As a result, TNFα signaling was detected in murine CML stem cells. TNFα expression was induced by ectopic expression of Bcr-Abl in murine and human progenitor cell lines. Clonogenic growth of CML cells was diminished by in vitro exposure to human or murine TNFα antibody.

“Interestingly, TNFα antibody treatment enhanced tyrosine kinase inhibitor–induced effects on immature cells in vitro,” the investigators commented. “Additionally, in transplant and serial transplant experiments, using our transgenic CML mouse model, we could subsequently show that infliximab therapy boosted tyrosine kinase inhibitor–induced effects and further reduced the proportion of malignant stem cells in vivo.”

Disclosure: The study authors’ disclosure information can be found at

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