Volatile Phases Derived from Serum, DC, or MLC Culture Supernatants to Deduce a VOC-Based Diagnostic Profiling Strategy for Leukemic Diseases

Volatile organic compounds (VOCs) reflect the metabolism in healthy and pathological conditions, and can be collected easily in a noninvasive manner. They are directly measured using electronical nose (eNose), and may qualify as a systemic tool to monitor biomarkers related to disease. Myeloid leuke...

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Main Authors: Tobias Baudrexler, Tobias Boeselt, Lin Li, Sophia Bohlscheid, Ursel Boas, Christoph Schmid, Andreas Rank, Jörg Schmohl, Rembert Koczulla, Helga Maria Schmetzer
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/13/6/989
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author Tobias Baudrexler
Tobias Boeselt
Lin Li
Sophia Bohlscheid
Ursel Boas
Christoph Schmid
Andreas Rank
Jörg Schmohl
Rembert Koczulla
Helga Maria Schmetzer
author_facet Tobias Baudrexler
Tobias Boeselt
Lin Li
Sophia Bohlscheid
Ursel Boas
Christoph Schmid
Andreas Rank
Jörg Schmohl
Rembert Koczulla
Helga Maria Schmetzer
author_sort Tobias Baudrexler
collection DOAJ
description Volatile organic compounds (VOCs) reflect the metabolism in healthy and pathological conditions, and can be collected easily in a noninvasive manner. They are directly measured using electronical nose (eNose), and may qualify as a systemic tool to monitor biomarkers related to disease. Myeloid leukemic blasts can be transformed into leukemia-derived dendritic cells (DC<sub>leu</sub>) able to improve (anti-leukemic) immune responses. To profile immunological changes in healthy and acute myeloid leukemic (AML) patients’ ex vivo cell cultures, we correlated the cell biological data with the profiles of cell culture supernatant-derived VOCs. DC/DC<sub>leu</sub> from leukemic or healthy whole blood (WB) were generated without (Control) or with immunomodulatory Kit M (Granulocyte macrophage-colony-stimulating-factor (GM-CSF) + prostaglandin E<sub>1</sub> (PGE<sub>1</sub>)) in dendritic cell cultures (DC culture). Kit-pretreated/not pretreated WB was used to stimulate T cell-enriched immunoreactive cells in mixed lymphocyte cultures (MLC culture). Leukemia-specific adaptive and innate immune cells were detected with a degranulation assay (Deg) and an intracellular cytokine assay (InCyt). Anti-leukemic cytotoxicity was explored with a cytotoxicity fluorolysis assay (CTX). VOCs collected from serum or DC- and MLC culture supernatants (with vs. without Kit M pretreatment and before vs. after culture) were measured using eNose. Compared to the Control (without treatment), Kit M-pretreated leukemic and healthy WB gave rise to higher frequencies of mature (leukemia-derived) DC subtypes of activated and (memory) T cells after MLC. Moreover, antigen (leukemia)-specific cells of several lines (innate and adaptive immunity cells) were induced, giving rise to blast-lysing cells. The eNose could significantly distinguish between healthy and leukemic patients’ serum, DC and MLC culture supernatant-derived volatile phases and could significantly separate several supernatant (with vs. without Kit M treatment, cultured vs. uncultured)-derived VOCs within subgroups (healthy DC or leukemic DC, or healthy MLC or leukemic MLC supernatants). Interestingly, the eNose could indicate a Kit M- and culture-associated effect. The eNose may be a prospective option for the deduction of a VOC-based profiling strategy using serum or cell culture supernatants and could be a useful diagnostic tool to recognize or qualify AML disease.
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spelling doaj.art-37e145deef0e4e82ae4fe70efe8ca2132023-11-18T09:31:36ZengMDPI AGBiomolecules2218-273X2023-06-0113698910.3390/biom13060989Volatile Phases Derived from Serum, DC, or MLC Culture Supernatants to Deduce a VOC-Based Diagnostic Profiling Strategy for Leukemic DiseasesTobias Baudrexler0Tobias Boeselt1Lin Li2Sophia Bohlscheid3Ursel Boas4Christoph Schmid5Andreas Rank6Jörg Schmohl7Rembert Koczulla8Helga Maria Schmetzer9Medical Department III, Hospital Großhadern, Ludwig-Maximilians-University, 81377 Munich, GermanyDepartment of Pulmonary Rehabilitation, German Center for Lung Research (DZL), Phillipps-University of Marburg, 35043 Marburg, GermanyMedical Department III, Hospital Großhadern, Ludwig-Maximilians-University, 81377 Munich, GermanyMedical Department III, Hospital Großhadern, Ludwig-Maximilians-University, 81377 Munich, GermanyDepartment of Pulmonary Rehabilitation, German Center for Lung Research (DZL), Phillipps-University of Marburg, 35043 Marburg, GermanyDepartment of Hematology and Oncology, University Hospital of Augsburg, 86156 Augsburg, GermanyDepartment of Hematology and Oncology, University Hospital of Augsburg, 86156 Augsburg, GermanyDepartment of Hematology and Oncology, Diaconia Hospital Stuttgart, 70176 Stuttgart, GermanyDepartment of Pulmonary Rehabilitation, German Center for Lung Research (DZL), Phillipps-University of Marburg, 35043 Marburg, GermanyMedical Department III, Hospital Großhadern, Ludwig-Maximilians-University, 81377 Munich, GermanyVolatile organic compounds (VOCs) reflect the metabolism in healthy and pathological conditions, and can be collected easily in a noninvasive manner. They are directly measured using electronical nose (eNose), and may qualify as a systemic tool to monitor biomarkers related to disease. Myeloid leukemic blasts can be transformed into leukemia-derived dendritic cells (DC<sub>leu</sub>) able to improve (anti-leukemic) immune responses. To profile immunological changes in healthy and acute myeloid leukemic (AML) patients’ ex vivo cell cultures, we correlated the cell biological data with the profiles of cell culture supernatant-derived VOCs. DC/DC<sub>leu</sub> from leukemic or healthy whole blood (WB) were generated without (Control) or with immunomodulatory Kit M (Granulocyte macrophage-colony-stimulating-factor (GM-CSF) + prostaglandin E<sub>1</sub> (PGE<sub>1</sub>)) in dendritic cell cultures (DC culture). Kit-pretreated/not pretreated WB was used to stimulate T cell-enriched immunoreactive cells in mixed lymphocyte cultures (MLC culture). Leukemia-specific adaptive and innate immune cells were detected with a degranulation assay (Deg) and an intracellular cytokine assay (InCyt). Anti-leukemic cytotoxicity was explored with a cytotoxicity fluorolysis assay (CTX). VOCs collected from serum or DC- and MLC culture supernatants (with vs. without Kit M pretreatment and before vs. after culture) were measured using eNose. Compared to the Control (without treatment), Kit M-pretreated leukemic and healthy WB gave rise to higher frequencies of mature (leukemia-derived) DC subtypes of activated and (memory) T cells after MLC. Moreover, antigen (leukemia)-specific cells of several lines (innate and adaptive immunity cells) were induced, giving rise to blast-lysing cells. The eNose could significantly distinguish between healthy and leukemic patients’ serum, DC and MLC culture supernatant-derived volatile phases and could significantly separate several supernatant (with vs. without Kit M treatment, cultured vs. uncultured)-derived VOCs within subgroups (healthy DC or leukemic DC, or healthy MLC or leukemic MLC supernatants). Interestingly, the eNose could indicate a Kit M- and culture-associated effect. The eNose may be a prospective option for the deduction of a VOC-based profiling strategy using serum or cell culture supernatants and could be a useful diagnostic tool to recognize or qualify AML disease.https://www.mdpi.com/2218-273X/13/6/989leukemia-derived DCacute myeloid leukemiaanti-leukemia functionalityleukemia-specific cellsvolatile phases above serum and cell culture supernatantsimmune monitoring
spellingShingle Tobias Baudrexler
Tobias Boeselt
Lin Li
Sophia Bohlscheid
Ursel Boas
Christoph Schmid
Andreas Rank
Jörg Schmohl
Rembert Koczulla
Helga Maria Schmetzer
Volatile Phases Derived from Serum, DC, or MLC Culture Supernatants to Deduce a VOC-Based Diagnostic Profiling Strategy for Leukemic Diseases
Biomolecules
leukemia-derived DC
acute myeloid leukemia
anti-leukemia functionality
leukemia-specific cells
volatile phases above serum and cell culture supernatants
immune monitoring
title Volatile Phases Derived from Serum, DC, or MLC Culture Supernatants to Deduce a VOC-Based Diagnostic Profiling Strategy for Leukemic Diseases
title_full Volatile Phases Derived from Serum, DC, or MLC Culture Supernatants to Deduce a VOC-Based Diagnostic Profiling Strategy for Leukemic Diseases
title_fullStr Volatile Phases Derived from Serum, DC, or MLC Culture Supernatants to Deduce a VOC-Based Diagnostic Profiling Strategy for Leukemic Diseases
title_full_unstemmed Volatile Phases Derived from Serum, DC, or MLC Culture Supernatants to Deduce a VOC-Based Diagnostic Profiling Strategy for Leukemic Diseases
title_short Volatile Phases Derived from Serum, DC, or MLC Culture Supernatants to Deduce a VOC-Based Diagnostic Profiling Strategy for Leukemic Diseases
title_sort volatile phases derived from serum dc or mlc culture supernatants to deduce a voc based diagnostic profiling strategy for leukemic diseases
topic leukemia-derived DC
acute myeloid leukemia
anti-leukemia functionality
leukemia-specific cells
volatile phases above serum and cell culture supernatants
immune monitoring
url https://www.mdpi.com/2218-273X/13/6/989
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