NMR-based metabolomic analysis of the molecular pathogenesis of therapy-related myelodysplasia/acute myeloid leukemia

Kristin E. Cano, Liang Li, Smita Bhatia, Ravi Bhatia, Stephen J. Forman, Yuan Chen

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Hematopoietic stem cell transplantation is the oldest and most successful form of stem cell therapy. High dose therapy (HDT) followed by hematopoietic stem cell transplantation allows physicians to administer increased amounts of chemotherapy and/or radiation while minimizing negative side effects such as damage to blood-producing bone marrow cells. Although HDT is successful in treating a wide range of cancers, it leads to lethal therapy-related myelodysplasia syndrome or acute myeloid leukemia (t-MDS/AML) in 5-10% of patients undergoing autologous hematopoietic cell transplantation for Hodgkin lymphoma and non-Hodgkin lymphoma. In this study, we carried out metabolomic analysis of peripheral blood stem cell samples collected in a cohort of patients before hematopoietic cell transplantation to gain insights into the molecular and cellular pathogenesis of t-MDS. Nonparametric tests and multivariate analyses were used to compare the metabolite concentrations in samples from patients that developed t-MDS within 5 years of transplantation and the patients that did not. The results suggest that the development of t-MDS is associated with dysfunctions in cellular metabolic pathways. The top canonical pathways suggested by the metabolomic analysis include alanine and aspartate metabolism, glyoxylate and dicarboxylate metabolism, phenylalanine metabolism, citrate acid cycle, and aminoacyl-t-RNA biosynthesis. Dysfunctions in these pathways indicate mitochondrial dysfunction that would result in decreased ability to detoxify reactive oxygen species generated by chemo and radiation therapy, therefore leading to cancer-causing mutations. These observations suggest predisposing factors for the development of t-MDS.

Original languageEnglish (US)
Pages (from-to)2873-2881
Number of pages9
JournalJournal of Proteome Research
Volume10
Issue number6
DOIs
StatePublished - Jun 3 2011
Externally publishedYes

Keywords

  • leukemia
  • metabolomics
  • NMR
  • peripheral blood stem cells

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Fingerprint

Dive into the research topics of 'NMR-based metabolomic analysis of the molecular pathogenesis of therapy-related myelodysplasia/acute myeloid leukemia'. Together they form a unique fingerprint.

Cite this