Investigation of Leukemogenic Mechanisms using Metabolomic Approaches

Abstract

In the bone marrow, the rapid distribution of white blood cells, which agglomerate and ultimately associate with normal blood cells, characterizes leukemogenic processes. Leukemogenic system AML is a complex neoplastic disorder characterized by naive myeloid cell upsurge and bone marrow incompetence. AML is the most common form of leukemia that affects the elderly. One of the prognostic characteristics of this response is the predominance of triggering the FMS-like tyrosine kinase 3 mutations (FLT3), in particular the probability of internal tandem duplication (FLT3-ITD). AML has a poor prognosis of the FLT3-ITD mutation. Metabolic profiling is the ability to understand metabolite modality. In this study, we attempted to understand AML with FLT3 from a metabolomic perspective. It has identified all the metabolites involved in Acute Myeloid Leukemia (AML) and their pathways. AML is a hematologic disease arising from the proliferation and intensification of malignant myeloid cells. In the past, fewer metabolites, such as inborn metabolism defects, were used to diagnose complex metabolic diseases and monogenic disorders. The results of this study have helped to create metabolic pathways for patients FLT3 / ITD, and we have further investigated how these metabolites are relevant from a network biology perspective. With Cytoscape and its plug-ins, such as Metscape, we studied molecular networks. Metabolisms of arachidonic acid and purine in cell metabolites during glycolysis and gluconeogenesis in plasma metabolites are pathways with the greatest impact of AML FLT3 / ITD, urea cycle, and metabolism of arginine, proline, glutamate, aspartate, and asparagine metabolism.