Metabolic Profiling during Acute Myeloid Leukemia Progression Using Paired Clinical Bone Marrow Serum Samples

Abstract

Cellular metabolic changes reflect the characteristics of patients with acute myeloid leukemia (AML) caused by genetic variations, which are important in establishing AML treatment. However, little is known about the metabolic profile of patients with genetic variation-induced AML. Furthermore, the metabolites differ with disease progression. Here, metabolites in the bone marrow serum of ten patients with AML and healthy individuals were analyzed using gas chromatography–mass spectrometry. Compared with that in healthy individuals, expression of most metabolites decreased in patients with AML; hydroxylamine, 2-hydroxybutyric acid, monomethylphosphate, and ethylphosphate expression was unusually increased in the patients. We further examined serial metabolite changes across the initial diagnosis, postremission, and relapse phases. Patients with relapse showed increased metabolite expression compared with those in the diagnostic phase, confirming that patients with AML had aggressively modified leukemic cells. However, a clear difference in metabolite distribution was not observed between the diagnosis and complete remission phases, suggesting that the metabolic microenvironment did not change significantly despite complete remission. Interestingly, metabolite profiles differed with genetic variations in leukemic cells. Our results, which were obtained using paired samples collected during AML progression, provide valuable insights for identifying vulnerable targets in the AML metabolome and developing new treatment strategies.

Metabolic profile analysis in hematological malignancies

“…Recently, there has been greater interest among researchers in the field of hematopoietic and lymphoid cell neoplasms. There have been an increasing number of studies carried out assessing changes in metabolite concentrations, particularly in acute myeloid leukemia (AML) [15][16][17] and multiple myeloma (MM) [18][19][20]. Despite the significant development of diagnostic and therapeutic methods seen in recent years, some hematological diseases remain incurable.…”

Metabolomic profile of acute myeloid leukaemia parallels of prognosis and response to therapy

“…Some studies have attempted to examine global changes in metabolites to identify biomarkers associated with phenotypic changes in various cancers 1 , 3 . However, there are very few AML studies that involve metabolomics 4 – 7 . The closest research were conducted on bone marrow 4 and bone marrow serum samples 7 .…”

“…However, there are very few AML studies that involve metabolomics 4 – 7 . The closest research were conducted on bone marrow 4 and bone marrow serum samples 7 . Both studies utilize metabolomics profiling, yet they employ methodologies distinct from ours.…”