Profiling of Metabolic Differences between Hematopoietic Stem Cells and Acute/Chronic Myeloid Leukemia.

Byung Hoo Song,Aeli Ryu,Hee Yong Chung,Hyun Kyu Kim,Su Young Son,Jeong Suk Im,Man Ryul Lee,Choong Hwan Lee,Jae Sang Oh,Tae Won Ha,Hyeji Jeon

doi:10.3390/metabo10110427

Byung Hoo Song, Aeli Ryu + Show 9 more

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https://doi.org/10.3390/metabo10110427

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Abstract

Although many studies have been conducted on leukemia, only a few have analyzed the metabolomic profiles of various leukemic cells. In this study, the metabolomes of THP-1, U937, KG-1 (acute myelogenous leukemia, AML), K562 (chronic myelogenous leukemia, CML), and cord blood-derived CD34-positive hematopoietic stem cells (HSC) were analyzed using gas chromatography-mass spectrometry, and specific metabolic alterations were found using multivariate statistical analysis. Compared to HSCs, leukemia cell metabolomes were found to have significant alterations, among which three were related to amino acids, three to sugars, and five to fatty acids. Compared to CML, four metabolomes were observed specifically in AML. Given that overall more metabolites are present in leukemia cells than in HSCs, we observed that the activation of glycolysis and oxidative phosphorylation (OXPHOS) metabolism facilitated the incidence of leukemia and the proliferation of leukemic cells. Analysis of metabolome profiles specifically present in HSCs and leukemia cells greatly increases our basic understanding of cellular metabolic characteristics, which is valuable fundamental knowledge for developing novel anticancer drugs targeting leukemia metabolism.

Highlights

Leukemia, a type of hematologic malignancy, occurs when immature white blood cells grow abnormally
To analyze the specific metabolites of leukemia cells, three AML cell lines and one CML cell line were purchased from the American Type Culture Collection (ATCC)
These cells, alongside line were purchased from the American Type Culture Collection (ATCC)

Summary

Introduction

A type of hematologic malignancy, occurs when immature white blood cells grow abnormally. Leukemia is known to be related to carcinogenic genes, chromosomal abnormalities, or bone marrow damage caused by viruses, radiation, or chemicals. It can be acute or chronic, depending on Metabolites 2020, 10, 427; doi:10.3390/metabo10110427 www.mdpi.com/journal/metabolites. Metabolites 2020, 10, 427 its progress pattern It can be myeloid or lymphocytic in nature, depending on the type of white blood cells affected. To meet the increased nutritional demand, cancer cells undergo metabolic reprogramming of ATP via conversion of pyruvate to lactate rather than channeling it to the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) in mitochondria [5,6]. Metabolic profiling research has drawn much attention as an approach for immediate detection of dynamic cellular alteration and status, such as oncogenesis

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