Impact of acute lymphoblastic leukemia induction therapy: findings from metabolomics on non-fasted plasma samples from a biorepository

• Published in: Metabolomics Vol. 17; no. 7; p. 64
• Main Authors: Saito, Toshie, Wei, Yue, Wen, Li, Srinivasan, Chaitanya, Wolthers, Benjamin O., Tsai, Cheng-Yu, Harris, Marian H., Stevenson, Kristen, Byersdorfer, Craig, Oparaji, Judy-April, Fernandez, Christian, Mukherjee, Amitava, Abu-El-Haija, Maisam, Agnihotri, Sameer, Schmiegelow, Kjeld, Showalter, Megan R., Fogle, Paul W., McCulloch, Scott, Contrepois, Kevin, Silverman, Lewis B., Ding, Ying, Husain, Sohail Z.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-07-2021; Springer Nature B.V
• Subjects: Acute lymphoblastic leukemia; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Chemotherapy; Child; Developmental Biology; Docosahexaenoic acid; Fatty acids; Humans; Induction Chemotherapy; Induction therapy; Leukemia; Life Sciences; Lipid metabolism; Lipids; Lymphatic leukemia; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Metabolomics; Molecular Medicine; Original Article; Phosphatidylethanolamine; Plasma; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Scientific imaging; Tandem Mass Spectrometry; Metabolomics; Lipidomics; Asparaginase phosphatidylethanolamine; Acute lymphoblastic leukemia; Triacylglycerol
• ISSN: 1573-3882; 1573-3890; 1573-3890
• DOI: 10.1007/s11306-021-01814-2

Introduction
Acute lymphoblastic leukemia (ALL) is among the most common cancers in children. With improvements in combination chemotherapy regimens, the overall survival has increased to over 90%. However, the current challenge is to mitigate adverse events resulting from the complex therapy. Several chemotherapies intercept cancer metabolism, but little is known about their collective role in altering host metabolism.
Objectives
We profiled the metabolomic changes in plasma of ALL patients initial- and post- induction therapy.
Methods
We exploited a biorepository of non-fasted plasma samples derived from the Dana Farber Cancer Institute ALL Consortium; these samples were obtained from 50 ALL patients initial- and post-induction therapy. Plasma metabolites and complex lipids were analyzed by high resolution tandem mass spectrometry and differential mobility tandem mass spectrometry. Data were analyzed using a covariate-adjusted regression model with multiplicity adjustment. Pathway enrichment analysis and co-expression network analysis were performed to identify unique clusters of molecules.
Results
More than 1200 metabolites and complex lipids were identified in the total of global metabolomics and lipidomics platforms. Over 20% of those molecules were significantly altered. In the pathway enrichment analysis, lipids, particularly phosphatidylethanolamines (PEs), were identified. Network analysis indicated that the bioactive fatty acids, docosahexaenoic acid (DHA)-containing (22:6) triacylglycerols (TAGs), were decreased in the post-induction therapy.
Conclusion
Metabolomic profiling in ALL patients revealed a large number of alterations following induction chemotherapy. In particular, lipid metabolism was substantially altered. The changes in metabolites and complex lipids following induction therapy could provide insight into the adverse events experienced by ALL patients.