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J Med Oncl Ther 2017 Volume 2 | Issue 3
International Conference on
Oncology and Cancer Therapeutics
October 30- November 01, 2017 | Chicago, USA
Metabolic flux analysis of mantle lymphoma cells upon Bruton tyrosine kinase inhibition
Seung-Cheol Lee
University of Pennsylvania, USA
Ibrutinib, a Bruton tyrosine kinase inhibitor, is being popularly
used for treatment of relapsed/refractory mantle cell
lymphoma (MCL) as well as chronic lymphocytic leykemia/
small lymphocytic lymphoma (CLL/SLL). We are working
on metabolic pathway analysis of MCL cells upon ibrutinib
treatment using novel 13C NMR and mass spectrometry
technique and flux analysis methods. Ibrutinib sensitive
MCL-RL cells and ibrutinib less sensitive Jeko-1 cells were
studied. Cells were incubated in the medium containing 1,6-
13C glucose, 1,2-13C glucose or U-13C glutamine for 8 hours
to reach steady state of labeling enrichment of intracellular
metabolites, and 13C labeling information was obtained
using NMR or liquid chromatography mass spectrometry (LC-
MS) techniques. Bonded cumomer and fragmented cumomer
analysis methods were employed for analysis of NMR and LC-
MS data. Significant changes were observed in the fluxes of
glycolysis, glutaminolysis, reductive carboxylation and fatty
acid syntheis in MCL-RL cells after ibrutnib treatment while
less or no changes in JeKo-1 cells. Glycolytic flux changed to1/4
in MCL-RL cells while to 1/2 in in JeKo-1 cells. Glutaminolysis
changed by 90% in MCL-RL cells while no change in JeKo-1
cells. When a glutaminase inhibitor, CB-839, was added to
medium, JeKo-1 cells exhbited remarkable response in cell
growth while MCL-RL cells did not. This study demonstrates
that metabolic flux analysis provides an important clue of
what pathway is being affected and what pathway is not
to specific kiniase inhibitors and which metabolic pathway
should be further targeted with additional drugs.
Speaker Biography
Seung-Cheol Lee has finishes his BS (Physics) from Korea Advanced Institute of Science
and Technology in 1993 and MS (Solid State Physics) from Korea Advanced Institute of
Science and Technology in 1995. After that, he did his Post-Graduate Training (Postdoc
in Biophysics) from Korea Basic Science Institute (2001-2004) and Postdoc in Radiology
from University of Pennsylvania (2004-2007). He has expertise in MRI and MRS of
cancer cells, animal models and human patients’ prediction and early detection of
therapeutic response in non-Hodgkin’s lymphoma.
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