Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemia

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalJournal of Hematology and Oncology
Volume9
Issue number1
DOIs
Publication statusPublished - Oct 28 2016

Fingerprint

Heterografts
Acute Myeloid Leukemia
Metabolomics
Magnetic Resonance Spectroscopy
Systems Biology
Genetic Heterogeneity
Dermatoglyphics
Leukemia
Clinical Trials
Drug Therapy

Keywords

  • Acute myeloid leukemia
  • Metabolomics
  • Nuclear magnetic resonance
  • Patient-derived xenografts

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemia. / Carrabba, Matteo G.; Tavel, Laurette; Oliveira, Giacomo; Forcina, Alessandra; Quilici, Giacomo; Nardelli, Francesca; Tresoldi, Cristina; Ambrosi, Alessandro; Ciceri, Fabio; Bernardi, Massimo; Vago, Luca; Musco, Giovanna.

In: Journal of Hematology and Oncology, Vol. 9, No. 1, 28.10.2016, p. 1-5.

Research output: Contribution to journalArticle

Carrabba, Matteo G. ; Tavel, Laurette ; Oliveira, Giacomo ; Forcina, Alessandra ; Quilici, Giacomo ; Nardelli, Francesca ; Tresoldi, Cristina ; Ambrosi, Alessandro ; Ciceri, Fabio ; Bernardi, Massimo ; Vago, Luca ; Musco, Giovanna. / Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemia. In: Journal of Hematology and Oncology. 2016 ; Vol. 9, No. 1. pp. 1-5.
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