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Papers by Diane Jelinek

Research paper thumbnail of Biologic and genetic characterization of the novel amyloidogenic lambda light chain–secreting human cell lines, ALMC-1 and ALMC-2

Blood, 2008

Primary systemic amyloidosis (AL) is a rare monoclonal plasma cell (PC) disorder characterized by... more Primary systemic amyloidosis (AL) is a rare monoclonal plasma cell (PC) disorder characterized by the deposition of misfolded immunoglobulin (Ig) light chains (LC) in vital organs throughout the body. To our knowledge, no cell lines have ever been established from AL patients. Here we describe the establishment of the ALMC-1 and ALMC-2 cell lines from an AL patient. Both cell lines exhibit a PC phenotype and display cytokine-dependent growth. Using a comprehensive genetic approach, we established the genetic relationship between the cell lines and the primary patient cells, and we were also able to identify new genetic changes accompanying tumor progression that may explain the natural history of this patient's disease. Importantly, we demonstrate that free lambda LC secreted by both cell lines contained a beta structure and formed amyloid fibrils. Despite absolute Ig LC variable gene sequence identity, the proteins show differences in amyloid formation kinetics that are abolish...

Research paper thumbnail of Multiple myeloma dell-derived microvesicles are enriched in CD147 expression and enhance tumor cell proliferation

Oncotarget, Jan 30, 2014

Multiple myeloma (MM) is characterized by the clonal expansion of malignant plasma cells within t... more Multiple myeloma (MM) is characterized by the clonal expansion of malignant plasma cells within the bone marrow. There is a growing literature that tumor cells release biologically active microvesicles (MVs) that modify both local and distant microenvironments. In this study, our goals were to determine if MM cells release MVs, and if so, begin to characterize their biologic activity. Herein we present clear evidence that not only do both patient MM cells and human MM cell lines (HMCLs) release MVs, but that these MVs stimulate MM cell growth. Of interest, MM-derived MVs were enriched with the biologically active form of CD147, a transmembrane molecule previously shown by us to be crucial for MM cell proliferation. Using MVs isolated from HMCLs stably transfected with a CD147-GFP fusion construct (CD147GFP), we observed binding and internalization of MV-derived CD147 with HMCLs. Cells with greater CD147GFP internalization proliferated at a higher rate than did cells with less CD147GFP association. Lastly, MVs obtained from CD147 downregulated HMCLs were attenuated in their ability to stimulate HMCL proliferation. In summary, this study demonstrates the significance of MV shedding and MV-mediated intercellular communication on malignant plasma cell proliferation, and identifies the role of MV-enriched CD147 in this process.

Research paper thumbnail of Proteomic detection of immunoglobulin light chain variable region peptides from amyloidosis patient biopsies

Journal of Proteome Research, 2015

Immunoglobulin light chain (LC) amyloidosis (AL) is caused by deposition of clonal LCs produced b... more Immunoglobulin light chain (LC) amyloidosis (AL) is caused by deposition of clonal LCs produced by an underlying plasma cell neoplasm. The clonotypic LC sequences are unique to each patient and they cannot be reliably detected by either immunoassays or standard proteomic workflows that target the constant regions of LCs. We addressed this issue by developing a novel sequence template-based workflow to detect LC variable (LCV) region peptides directly from AL amyloid deposits. The workflow was implemented in a CAP/CLIA compliant clinical laboratory dedicated to proteomic subtyping of amyloid deposits extracted from either formalin-fixed paraffin-embedded tissues or subcutaneous fat aspirates. We evaluated the performance of the workflow on a validation cohort of 30 AL patients, whose amyloidogenic clone was identified using a novel proteogenomics method, and 30 controls. The recall and negative predictive value of the workflow, when identifying the gene family of the AL clone, was 93% and 98%, respectively. Application of the workflow on a clinical cohort of 500 AL amyloidosis samples highlighted a bias in the LCV gene families used by the AL clones. We also detected similarity between AL clones deposited in multiple organs of systemic AL patients. In summary, AL proteomic data sets are rich in LCV region peptides of potential clinical significance that are recoverable with advanced bioinformatics.

Research paper thumbnail of Faculty of 1000 evaluation for The tyrosine kinase Lyn limits the cytokine responsiveness of plasma cells to restrict their accumulation in mice

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Regulation of Human B Cell Proliferation and Differentiation by Interleukin 2

The Molecular Basis of B-Cell Differentiation and Function, 1986

Research paper thumbnail of Faculty of 1000 evaluation for Kruppel-like factor 4 blocks tumor cell proliferation and promotes drug resistance in multiple myeloma

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Multiple myeloma patients have a specific serum metabolomic profile that changes after achieving complete remission

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for CD49d is overexpressed by trisomy 12 chronic lymphocytic leukemia cells: evidence for a methylation-dependent regulation mechanism

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Fas apoptosis inhibitory molecule is upregulated by IGF-1 signaling and modulates Akt activation and IRF4 expression in multiple myeloma

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Detailed characterization of multiple myeloma circulating tumor cells shows unique phenotypic, cytogenetic, functional and circadian distribution profile

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Two levels of protection for the B cell genome during somatic hypermutation

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Development of immunoglobulin lambda-chain-positive B cells, but not editing of immunoglobulin kappa-chain, depends on NF-kappaB signals

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Immunoglobulin heavy/light chain ratios improve paraprotein detection and monitoring, identify residual disease and correlate with survival in multiple myeloma patients

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Characterization of IgH breakpoints in multiple myeloma indicates a subset of translocations appear to occur in pre-germinal center B cells

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Reversible anergy of sIgM-mediated signaling in the two subsets of CLL defined by VH-gene mutational status

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Downregulation of specific miRNAs in hyperdiploid multiple myeloma mimics the oncogenic effect of IgH translocations occurring in the non-hyperdiploid subtype

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for AID-Driven Deletion Causes Immunoglobulin Heavy Chain "Locus Suicide Recombination" in B Cells

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Reconstructing the human hematopoietic niche in immune deficient mice, opportunities for studying primary multiple myeloma

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Biologic and genetic characterization of the novel amyloidogenic lambda light chain–secreting human cell lines, ALMC-1 and ALMC-2

Blood, 2008

Primary systemic amyloidosis (AL) is a rare monoclonal plasma cell (PC) disorder characterized by... more Primary systemic amyloidosis (AL) is a rare monoclonal plasma cell (PC) disorder characterized by the deposition of misfolded immunoglobulin (Ig) light chains (LC) in vital organs throughout the body. To our knowledge, no cell lines have ever been established from AL patients. Here we describe the establishment of the ALMC-1 and ALMC-2 cell lines from an AL patient. Both cell lines exhibit a PC phenotype and display cytokine-dependent growth. Using a comprehensive genetic approach, we established the genetic relationship between the cell lines and the primary patient cells, and we were also able to identify new genetic changes accompanying tumor progression that may explain the natural history of this patient's disease. Importantly, we demonstrate that free lambda LC secreted by both cell lines contained a beta structure and formed amyloid fibrils. Despite absolute Ig LC variable gene sequence identity, the proteins show differences in amyloid formation kinetics that are abolish...

Research paper thumbnail of Multiple myeloma dell-derived microvesicles are enriched in CD147 expression and enhance tumor cell proliferation

Oncotarget, Jan 30, 2014

Multiple myeloma (MM) is characterized by the clonal expansion of malignant plasma cells within t... more Multiple myeloma (MM) is characterized by the clonal expansion of malignant plasma cells within the bone marrow. There is a growing literature that tumor cells release biologically active microvesicles (MVs) that modify both local and distant microenvironments. In this study, our goals were to determine if MM cells release MVs, and if so, begin to characterize their biologic activity. Herein we present clear evidence that not only do both patient MM cells and human MM cell lines (HMCLs) release MVs, but that these MVs stimulate MM cell growth. Of interest, MM-derived MVs were enriched with the biologically active form of CD147, a transmembrane molecule previously shown by us to be crucial for MM cell proliferation. Using MVs isolated from HMCLs stably transfected with a CD147-GFP fusion construct (CD147GFP), we observed binding and internalization of MV-derived CD147 with HMCLs. Cells with greater CD147GFP internalization proliferated at a higher rate than did cells with less CD147GFP association. Lastly, MVs obtained from CD147 downregulated HMCLs were attenuated in their ability to stimulate HMCL proliferation. In summary, this study demonstrates the significance of MV shedding and MV-mediated intercellular communication on malignant plasma cell proliferation, and identifies the role of MV-enriched CD147 in this process.

Research paper thumbnail of Proteomic detection of immunoglobulin light chain variable region peptides from amyloidosis patient biopsies

Journal of Proteome Research, 2015

Immunoglobulin light chain (LC) amyloidosis (AL) is caused by deposition of clonal LCs produced b... more Immunoglobulin light chain (LC) amyloidosis (AL) is caused by deposition of clonal LCs produced by an underlying plasma cell neoplasm. The clonotypic LC sequences are unique to each patient and they cannot be reliably detected by either immunoassays or standard proteomic workflows that target the constant regions of LCs. We addressed this issue by developing a novel sequence template-based workflow to detect LC variable (LCV) region peptides directly from AL amyloid deposits. The workflow was implemented in a CAP/CLIA compliant clinical laboratory dedicated to proteomic subtyping of amyloid deposits extracted from either formalin-fixed paraffin-embedded tissues or subcutaneous fat aspirates. We evaluated the performance of the workflow on a validation cohort of 30 AL patients, whose amyloidogenic clone was identified using a novel proteogenomics method, and 30 controls. The recall and negative predictive value of the workflow, when identifying the gene family of the AL clone, was 93% and 98%, respectively. Application of the workflow on a clinical cohort of 500 AL amyloidosis samples highlighted a bias in the LCV gene families used by the AL clones. We also detected similarity between AL clones deposited in multiple organs of systemic AL patients. In summary, AL proteomic data sets are rich in LCV region peptides of potential clinical significance that are recoverable with advanced bioinformatics.

Research paper thumbnail of Faculty of 1000 evaluation for The tyrosine kinase Lyn limits the cytokine responsiveness of plasma cells to restrict their accumulation in mice

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Regulation of Human B Cell Proliferation and Differentiation by Interleukin 2

The Molecular Basis of B-Cell Differentiation and Function, 1986

Research paper thumbnail of Faculty of 1000 evaluation for Kruppel-like factor 4 blocks tumor cell proliferation and promotes drug resistance in multiple myeloma

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Multiple myeloma patients have a specific serum metabolomic profile that changes after achieving complete remission

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for CD49d is overexpressed by trisomy 12 chronic lymphocytic leukemia cells: evidence for a methylation-dependent regulation mechanism

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Fas apoptosis inhibitory molecule is upregulated by IGF-1 signaling and modulates Akt activation and IRF4 expression in multiple myeloma

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Detailed characterization of multiple myeloma circulating tumor cells shows unique phenotypic, cytogenetic, functional and circadian distribution profile

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Two levels of protection for the B cell genome during somatic hypermutation

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Development of immunoglobulin lambda-chain-positive B cells, but not editing of immunoglobulin kappa-chain, depends on NF-kappaB signals

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Immunoglobulin heavy/light chain ratios improve paraprotein detection and monitoring, identify residual disease and correlate with survival in multiple myeloma patients

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Characterization of IgH breakpoints in multiple myeloma indicates a subset of translocations appear to occur in pre-germinal center B cells

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Reversible anergy of sIgM-mediated signaling in the two subsets of CLL defined by VH-gene mutational status

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Downregulation of specific miRNAs in hyperdiploid multiple myeloma mimics the oncogenic effect of IgH translocations occurring in the non-hyperdiploid subtype

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for AID-Driven Deletion Causes Immunoglobulin Heavy Chain "Locus Suicide Recombination" in B Cells

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Reconstructing the human hematopoietic niche in immune deficient mice, opportunities for studying primary multiple myeloma

F1000 - Post-publication peer review of the biomedical literature, 2000

Research paper thumbnail of Faculty of 1000 evaluation for Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation

F1000 - Post-publication peer review of the biomedical literature, 2000

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