Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemia
Abstract Despite the considerable progress in understanding the molecular bases of acute myeloid leukemia (AML), new tools to link disease biology to the unpredictable patient clinical course are still needed. Herein, high-throughput metabolomics, combined with the other “-omics” disciplines, holds...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2016-10-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13045-016-0346-2 |
| _version_ | 1811303800375345152 |
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| author | Matteo G. Carrabba Laurette Tavel Giacomo Oliveira Alessandra Forcina Giacomo Quilici Francesca Nardelli Cristina Tresoldi Alessandro Ambrosi Fabio Ciceri Massimo Bernardi Luca Vago Giovanna Musco |
| author_facet | Matteo G. Carrabba Laurette Tavel Giacomo Oliveira Alessandra Forcina Giacomo Quilici Francesca Nardelli Cristina Tresoldi Alessandro Ambrosi Fabio Ciceri Massimo Bernardi Luca Vago Giovanna Musco |
| author_sort | Matteo G. Carrabba |
| collection | DOAJ |
| description | Abstract Despite the considerable progress in understanding the molecular bases of acute myeloid leukemia (AML), new tools to link disease biology to the unpredictable patient clinical course are still needed. Herein, high-throughput metabolomics, combined with the other “-omics” disciplines, holds promise in identifying disease-specific and clinically relevant features. In this study, we took advantage of nuclear magnetic resonance (NMR) to trace AML-associated metabolic trajectory employing two complementary strategies. On the one hand, we performed a prospective observational clinical trial to identify metabolic changes associated with blast clearance during the first two cycles of intensive chemotherapy in nine adult patients. On the other hand, to reduce the intrinsic variability associated with human samples and AML genetic heterogeneity, we analyzed the metabolic changes in the plasma of immunocompromised mice upon engraftment of primary human AML blasts. Combining the two longitudinal approaches, we narrowed our screen to seven common metabolites, for which we observed a mirror-like trajectory in mice and humans, tracing AML progression and remission, respectively. We interpreted this set of metabolites as a dynamic fingerprint of AML evolution. Overall, these NMR-based metabolomic data, to be consolidated in larger cohorts and integrated in more comprehensive system biology approaches, hold promise for providing valuable and non-redundant information on the systemic effects of leukemia. |
| first_indexed | 2024-04-13T07:54:37Z |
| format | Article |
| id | doaj.art-3ae6742c76094aa9b6051447d9c24fa2 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-04-13T07:54:37Z |
| publishDate | 2016-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-3ae6742c76094aa9b6051447d9c24fa22022-12-22T02:55:26ZengBMCJournal of Hematology & Oncology1756-87222016-10-01911510.1186/s13045-016-0346-2Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemiaMatteo G. Carrabba0Laurette Tavel1Giacomo Oliveira2Alessandra Forcina3Giacomo Quilici4Francesca Nardelli5Cristina Tresoldi6Alessandro Ambrosi7Fabio Ciceri8Massimo Bernardi9Luca Vago10Giovanna Musco11Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific InstituteBiomolecular Nuclear Magnetic Resonance Unit, IRCCS San Raffaele Scientific InstituteUnit of Immunogenetics, Leukemia Genomics and Immunobiology, IRCCS San Raffaele Scientific InstituteUnit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific InstituteBiomolecular Nuclear Magnetic Resonance Unit, IRCCS San Raffaele Scientific InstituteBiomolecular Nuclear Magnetic Resonance Unit, IRCCS San Raffaele Scientific InstituteMolecular Hematology Laboratory, IRCCS San Raffaele Scientific InstituteCenter for Statistics in Biomedical Sciences, University Vita-Salute San RaffaeleUnit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific InstituteUnit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific InstituteUnit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific InstituteBiomolecular Nuclear Magnetic Resonance Unit, IRCCS San Raffaele Scientific InstituteAbstract Despite the considerable progress in understanding the molecular bases of acute myeloid leukemia (AML), new tools to link disease biology to the unpredictable patient clinical course are still needed. Herein, high-throughput metabolomics, combined with the other “-omics” disciplines, holds promise in identifying disease-specific and clinically relevant features. In this study, we took advantage of nuclear magnetic resonance (NMR) to trace AML-associated metabolic trajectory employing two complementary strategies. On the one hand, we performed a prospective observational clinical trial to identify metabolic changes associated with blast clearance during the first two cycles of intensive chemotherapy in nine adult patients. On the other hand, to reduce the intrinsic variability associated with human samples and AML genetic heterogeneity, we analyzed the metabolic changes in the plasma of immunocompromised mice upon engraftment of primary human AML blasts. Combining the two longitudinal approaches, we narrowed our screen to seven common metabolites, for which we observed a mirror-like trajectory in mice and humans, tracing AML progression and remission, respectively. We interpreted this set of metabolites as a dynamic fingerprint of AML evolution. Overall, these NMR-based metabolomic data, to be consolidated in larger cohorts and integrated in more comprehensive system biology approaches, hold promise for providing valuable and non-redundant information on the systemic effects of leukemia.http://link.springer.com/article/10.1186/s13045-016-0346-2Acute myeloid leukemiaMetabolomicsPatient-derived xenograftsNuclear magnetic resonance |
| spellingShingle | Matteo G. Carrabba Laurette Tavel Giacomo Oliveira Alessandra Forcina Giacomo Quilici Francesca Nardelli Cristina Tresoldi Alessandro Ambrosi Fabio Ciceri Massimo Bernardi Luca Vago Giovanna Musco Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemia Journal of Hematology & Oncology Acute myeloid leukemia Metabolomics Patient-derived xenografts Nuclear magnetic resonance |
| title | Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemia |
| title_full | Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemia |
| title_fullStr | Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemia |
| title_full_unstemmed | Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemia |
| title_short | Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemia |
| title_sort | integrating a prospective pilot trial and patient derived xenografts to trace metabolic changes associated with acute myeloid leukemia |
| topic | Acute myeloid leukemia Metabolomics Patient-derived xenografts Nuclear magnetic resonance |
| url | http://link.springer.com/article/10.1186/s13045-016-0346-2 |
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