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On chip analysis of CNS lymphoma in cerebrospinal fluid.

Turetsky A, Lee K, Song J, Giedt RJ, Kim E, Kovach AE, Hochberg EP, Castro CM, Lee H, Weissleder R - Theranostics (2015)

Bottom Line: Molecular profiling of central nervous system lymphomas in cerebrospinal fluid (CSF) samples can be challenging due to the paucicellular and limited nature of the samples.The system can detect scant lymphoma cells and quantitate their kappa/lambda immunoglobulin light chain restriction patterns.The approach can be further customized for measurement of additional biomarkers, such as those for differential diagnosis of lymphoma subtypes or for prognosis, as well as for imaging exposure to experimental drugs.

View Article: PubMed Central - PubMed

Affiliation: 1. Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA.

ABSTRACT
Molecular profiling of central nervous system lymphomas in cerebrospinal fluid (CSF) samples can be challenging due to the paucicellular and limited nature of the samples. Presented herein is a microfluidic platform for complete CSF lymphoid cell analysis, including single cell capture in sub-nanoliter traps, and molecular and chemotherapeutic response profiling via on-chip imaging, all in less than one hour. The system can detect scant lymphoma cells and quantitate their kappa/lambda immunoglobulin light chain restriction patterns. The approach can be further customized for measurement of additional biomarkers, such as those for differential diagnosis of lymphoma subtypes or for prognosis, as well as for imaging exposure to experimental drugs.

No MeSH data available.


Related in: MedlinePlus

Theranostic on-chip imaging. BTK-positive Rec-1 cells or BTK-negative Jurkat T-cell leukemia cells using fluorescent BTK inhibitor (Ibrutinib-BFL), anti-CD20-APC, and Hoechst stain. Note the high drug uptake and binding in Rec-1 cells. Scale bar: 5 µm.
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Figure 6: Theranostic on-chip imaging. BTK-positive Rec-1 cells or BTK-negative Jurkat T-cell leukemia cells using fluorescent BTK inhibitor (Ibrutinib-BFL), anti-CD20-APC, and Hoechst stain. Note the high drug uptake and binding in Rec-1 cells. Scale bar: 5 µm.

Mentions: We further performed drug sensitivity testing that would be clinically useful to guide intrathecal and/or systemic chemo- and targeted therapies. We used a companion imaging drugs that has recently been reported, Ibrutinib-BFL, an inhibitor of Bruton's Tyrosine Kinase (BTK) 28; other imaging drugs include fluorescent rituximab or caged methotrexate. Ibrutinib is approved for several B-cell malignancies, including mantle cell lymphoma, and the Rec-1 cell line has been shown to be sensitive to the drug 29,30. Imaging the Rec-1 cells with Ibrutinib-BFL on the chip shows not only the binding of Ibrutinib, but also their cell-to-cell heterogeneity due to differences in BTK inhibitor sensitivity and BTK protein turnover (Fig. 6).


On chip analysis of CNS lymphoma in cerebrospinal fluid.

Turetsky A, Lee K, Song J, Giedt RJ, Kim E, Kovach AE, Hochberg EP, Castro CM, Lee H, Weissleder R - Theranostics (2015)

Theranostic on-chip imaging. BTK-positive Rec-1 cells or BTK-negative Jurkat T-cell leukemia cells using fluorescent BTK inhibitor (Ibrutinib-BFL), anti-CD20-APC, and Hoechst stain. Note the high drug uptake and binding in Rec-1 cells. Scale bar: 5 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4440438&req=5

Figure 6: Theranostic on-chip imaging. BTK-positive Rec-1 cells or BTK-negative Jurkat T-cell leukemia cells using fluorescent BTK inhibitor (Ibrutinib-BFL), anti-CD20-APC, and Hoechst stain. Note the high drug uptake and binding in Rec-1 cells. Scale bar: 5 µm.
Mentions: We further performed drug sensitivity testing that would be clinically useful to guide intrathecal and/or systemic chemo- and targeted therapies. We used a companion imaging drugs that has recently been reported, Ibrutinib-BFL, an inhibitor of Bruton's Tyrosine Kinase (BTK) 28; other imaging drugs include fluorescent rituximab or caged methotrexate. Ibrutinib is approved for several B-cell malignancies, including mantle cell lymphoma, and the Rec-1 cell line has been shown to be sensitive to the drug 29,30. Imaging the Rec-1 cells with Ibrutinib-BFL on the chip shows not only the binding of Ibrutinib, but also their cell-to-cell heterogeneity due to differences in BTK inhibitor sensitivity and BTK protein turnover (Fig. 6).

Bottom Line: Molecular profiling of central nervous system lymphomas in cerebrospinal fluid (CSF) samples can be challenging due to the paucicellular and limited nature of the samples.The system can detect scant lymphoma cells and quantitate their kappa/lambda immunoglobulin light chain restriction patterns.The approach can be further customized for measurement of additional biomarkers, such as those for differential diagnosis of lymphoma subtypes or for prognosis, as well as for imaging exposure to experimental drugs.

View Article: PubMed Central - PubMed

Affiliation: 1. Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA.

ABSTRACT
Molecular profiling of central nervous system lymphomas in cerebrospinal fluid (CSF) samples can be challenging due to the paucicellular and limited nature of the samples. Presented herein is a microfluidic platform for complete CSF lymphoid cell analysis, including single cell capture in sub-nanoliter traps, and molecular and chemotherapeutic response profiling via on-chip imaging, all in less than one hour. The system can detect scant lymphoma cells and quantitate their kappa/lambda immunoglobulin light chain restriction patterns. The approach can be further customized for measurement of additional biomarkers, such as those for differential diagnosis of lymphoma subtypes or for prognosis, as well as for imaging exposure to experimental drugs.

No MeSH data available.


Related in: MedlinePlus