Contributions
Abstract: PB1385
Type: Publication Only
Session title: Acute myeloid leukemia - Biology & Translational Research
Background
Inflammation may be particularly important in the context of monocyte-rich myeloid neoplasms. The discovery of drugs that prevent chronic or acute inflammation is a major goal of the pharmaceutical industry. A proof-of-concept screening showed that the BCR-ABL inhibitor nilotinib, but not the structurally similar imatinib, blocks the pro-inflammatory phenotype by MALDI-TOF.
Aims
Our main aim was to identify the off-targets proteins for nilotinib compared with imatinib in human immortalised monocytes derived from AML. And to study the differences between nilotinib and imatinib in the inflammatory response in acute myeloid leukemia and multiple myeloma cells.
Methods
In order to identify the off-targets for nilotinib, we performed a thermal proteome profiling (TPP) over a range of temperatures and compound concentrations. We validated the effects of these off-targets by western blot, RTqPCR, ELISA and flow cytometry experiments.
Results
We show that nilotinib affects MAPK signalling and, ultimately preventing the transcription of pro-inflammatory genes, cell adhesion markers and innate immunity markers.
Conclusion
In consequence, nilotinib may have therapeutic potential through the inhibition of MAPK pathway in inflammatory diseases as well as in myeloid malignancies such as myeloid leukemia and multiple myeloma.
Keyword(s): AML, Inflammation, Monocyte, Proteomics
Abstract: PB1385
Type: Publication Only
Session title: Acute myeloid leukemia - Biology & Translational Research
Background
Inflammation may be particularly important in the context of monocyte-rich myeloid neoplasms. The discovery of drugs that prevent chronic or acute inflammation is a major goal of the pharmaceutical industry. A proof-of-concept screening showed that the BCR-ABL inhibitor nilotinib, but not the structurally similar imatinib, blocks the pro-inflammatory phenotype by MALDI-TOF.
Aims
Our main aim was to identify the off-targets proteins for nilotinib compared with imatinib in human immortalised monocytes derived from AML. And to study the differences between nilotinib and imatinib in the inflammatory response in acute myeloid leukemia and multiple myeloma cells.
Methods
In order to identify the off-targets for nilotinib, we performed a thermal proteome profiling (TPP) over a range of temperatures and compound concentrations. We validated the effects of these off-targets by western blot, RTqPCR, ELISA and flow cytometry experiments.
Results
We show that nilotinib affects MAPK signalling and, ultimately preventing the transcription of pro-inflammatory genes, cell adhesion markers and innate immunity markers.
Conclusion
In consequence, nilotinib may have therapeutic potential through the inhibition of MAPK pathway in inflammatory diseases as well as in myeloid malignancies such as myeloid leukemia and multiple myeloma.
Keyword(s): AML, Inflammation, Monocyte, Proteomics