IN VIVO IMAGING OF LUMINESCENT DIFFUSE LARGE B-CELL LYMPHOMA XENOGRAFTS COMBINED WITH MASS SPECTROMETRY IMAGING IDENTIFY SPECIFIC MOLECULAR ALTERATION DURING R-CHOP RELAPSE.
(Abstract release date: 05/18/17)
EHA Library. COME C. 05/18/17; 182782; PB2068
Christophe COME
Contributions
Contributions
Abstract
Abstract: PB2068
Type: Publication Only
Background
Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin’s lymphoma (NHL) throughout the world, comprising 30–35% of all NHLs, with approximately 71 000 new cases and 19 000 deaths estimated for 2014. Currently, R-CHOP, a combination of immunotherapy (Rituximab, targeting the cell surface protein CD20 expressed by B cell lymphoma) and chemotherapy (Cyclophosphamide, doxorubicin, vincristine and prednisone), remains the most commonly used regimens for newly diagnosed advanced DLBCLs. However, as it is a biologically aggressive disease, up to one-third of patients will ultimately become refractory to initial therapy or relapse after treatment and display poor survival outcome, underlying the urgent need for novel therapeutic approaches based upon selective molecular targets.
We are combining in vivo luminescent/fluorescent DLBCL xenograft models with mass spectrometry imaging (MSI) analysis to study the tumors characteristics during R-CHOP treatment and relapse. The in vivo imaging approach allows us to precisely quantify tumoral development and response to therapy, as well as to differentiate tumoral cells from the tumoral micro-environment. On the other hand, MSI technique provides information regarding analyte composition at an almost cellular level. Therefore, we can identify, localize the molecules, proteins, drugs or metabolites. 2 types of analysis are performed: i) comparison between primary untreated tumors and tumors relapsing from R-CHOP therapy. ii) study of the therapy resistant and sensitive areas of each tumor.
Aims
Our aim is to investigate and analyze the various chemical composition of DLBCL xenografts during tumoral development and R-CHOP treatment relapse, in order to identify yet uncharacterized targets that could become alternative targets for therapy.
Methods
10 millions cells of a U2932 lymphoma cell line were xenografted into 60 athymic nude immuno-deficient mice . Tumoral growth was repeatedly quantified in a non-invasive manner based on tumors’ luminescent signal using the in vivo imaging system (IVIS) Lumina II. R-CHOP treatment was applied to mice after primary tumoral growth. 2 types of samples are generated: i) untreated tumors, ii) tumors realpsing from R-CHOP
Mass spectrometry imaging is then used to analyze and compare the chemical and biological profiles of DLBCL xenografts at these stages of tumoral growth.
Results
In vivo imaging allows us not only to precisely assess primary tumor development but more importantly, to monitor accurately response to R-CHOP and relapse from this therapy. The tumors at different stages of response to R-CHOP therapy are being analyzed and compared from lipidomics, metabolomics and proteomics point of view. Primary analysis indicate very distinctive metabolomics and lipidomic profiles between relapsed and non treated tumors.
Conclusion
Combining IVIS and MSI allow us for a better understanding of the disease and the treatment effects and the possible mechanisms allowing tumor cells to escape therapy. We are currently investigating in more details these different lipidomics, metabolomics or proteomics signatures between the different stages of DLBCL response to R-CHOP treatment in order to identify new candidates for alternative therapies.
Session topic: 18. Non-Hodgkin & Hodgkin lymphoma - Biology
Keyword(s): In vivo imaging, DLBCL, Relapsed lymphoma, Mouse model
Abstract: PB2068
Type: Publication Only
Background
Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin’s lymphoma (NHL) throughout the world, comprising 30–35% of all NHLs, with approximately 71 000 new cases and 19 000 deaths estimated for 2014. Currently, R-CHOP, a combination of immunotherapy (Rituximab, targeting the cell surface protein CD20 expressed by B cell lymphoma) and chemotherapy (Cyclophosphamide, doxorubicin, vincristine and prednisone), remains the most commonly used regimens for newly diagnosed advanced DLBCLs. However, as it is a biologically aggressive disease, up to one-third of patients will ultimately become refractory to initial therapy or relapse after treatment and display poor survival outcome, underlying the urgent need for novel therapeutic approaches based upon selective molecular targets.
We are combining in vivo luminescent/fluorescent DLBCL xenograft models with mass spectrometry imaging (MSI) analysis to study the tumors characteristics during R-CHOP treatment and relapse. The in vivo imaging approach allows us to precisely quantify tumoral development and response to therapy, as well as to differentiate tumoral cells from the tumoral micro-environment. On the other hand, MSI technique provides information regarding analyte composition at an almost cellular level. Therefore, we can identify, localize the molecules, proteins, drugs or metabolites. 2 types of analysis are performed: i) comparison between primary untreated tumors and tumors relapsing from R-CHOP therapy. ii) study of the therapy resistant and sensitive areas of each tumor.
Aims
Our aim is to investigate and analyze the various chemical composition of DLBCL xenografts during tumoral development and R-CHOP treatment relapse, in order to identify yet uncharacterized targets that could become alternative targets for therapy.
Methods
10 millions cells of a U2932 lymphoma cell line were xenografted into 60 athymic nude immuno-deficient mice . Tumoral growth was repeatedly quantified in a non-invasive manner based on tumors’ luminescent signal using the in vivo imaging system (IVIS) Lumina II. R-CHOP treatment was applied to mice after primary tumoral growth. 2 types of samples are generated: i) untreated tumors, ii) tumors realpsing from R-CHOP
Mass spectrometry imaging is then used to analyze and compare the chemical and biological profiles of DLBCL xenografts at these stages of tumoral growth.
Results
In vivo imaging allows us not only to precisely assess primary tumor development but more importantly, to monitor accurately response to R-CHOP and relapse from this therapy. The tumors at different stages of response to R-CHOP therapy are being analyzed and compared from lipidomics, metabolomics and proteomics point of view. Primary analysis indicate very distinctive metabolomics and lipidomic profiles between relapsed and non treated tumors.
Conclusion
Combining IVIS and MSI allow us for a better understanding of the disease and the treatment effects and the possible mechanisms allowing tumor cells to escape therapy. We are currently investigating in more details these different lipidomics, metabolomics or proteomics signatures between the different stages of DLBCL response to R-CHOP treatment in order to identify new candidates for alternative therapies.
Session topic: 18. Non-Hodgkin & Hodgkin lymphoma - Biology
Keyword(s): In vivo imaging, DLBCL, Relapsed lymphoma, Mouse model
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