Lipidomic approach for stratification of Acute Myeloid Leukemia patients

TL;DR

This study uses lipidomic profiling via shotgun MS to distinguish AML patient subtypes based on their lipid signatures, revealing significant differences in ceramide/sphingolipid levels and membrane properties that could aid diagnosis.

Contribution

It provides the first detailed lipidomic comparison of AML subtypes, highlighting lipid profile differences as potential diagnostic markers.

Findings

Distinct lipid signatures identified for AML subtypes

Significant modulation of ceramides and sphingolipids in specific AML types

Altered membrane saturation levels linked to AML genetic variations

Abstract

The pathogenesis and progression of many tumors, including hematologic malignancies is highly dependent on enhanced lipogenesis. De novo fatty-acid synthesis permits accelerated proliferation of tumor cells by providing structural components to build the membranes. It may also lead to alterations of physicochemical properties of the formed membranes, which can have an impact on signaling or even increase resistance to drugs in cancer cells. Cancer type-specific lipid profiles would allow understanding the actual effects of lipid changes and therefore could potentially serve as fingerprints for individual tumors and be explored as diagnostic markers. We have used shotgun MS approach to identify lipid patterns in different types of acute myeloid leukemia (AML) patients that either show no karyotype changes or belong to t(8;21) or inv16 types. The observed differences in lipidomes of t(8;21) and inv(16) patients, as compared to AML patients without karyotype changes, concentrate mostly on substantial modulation of ceramides/sphingolipids synthesis. Also significant changes in the physicochemical properties of the membranes, between the t(8;21) and the other patients, were noted that were related to a marked alteration in the saturation levels of lipids. The revealed differences in lipid profiles of various AML types increase our understanding of the affected biochemical pathways and can potentially serve as diagnostic tools.