title: Lipidomic approach for stratification of acute myeloid leukemia patients.
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 membrane components but these may also alter physicochemical properties of lipid bilayers, which can impact signaling or even increase drug resistance in cancer cells. Cancer type-specific lipid profiles would permit us to monitor and interpret actual effects of lipid changes, potential fingerprints of individual tumors to be explored as diagnostic markers. We have used the shotgun MS approach to identify lipid patterns in different types of acute myeloid leukemia (AML) patients that either show no karyotype change or belong to t(8;21) or inv16 types. Differences in lipidomes of t(8;21) and inv(16) patients, as compared to AML patients without karyotype change, presented mostly as substantial modulation of ceramide/sphingolipid synthesis. Furthermore, between the t(8;21) and all other patients we observed significant changes in physicochemical membrane properties. These were related to a marked alteration in lipid saturation levels. The discovered differences in lipid profiles of various AML types improve our understanding of the pathobiochemical pathways involved and may serve in the development of diagnostic tools.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Adam
authors.initials: A
authors.lastname: Stefanko
authors.affiliation: Medical Clinic and Polyclinic I, University Hospital TU Dresden, Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
authors.affiliation: Medical Clinic and Polyclinic I, University Hospital TU Dresden, Dresden, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.|Lipotype GmbH, Dresden, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Simons
authors.affiliation: Paul Langerhans Institute Dresden of the Helmholtz Centre Munich at the University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany.|German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
authors.forename: Michal
authors.initials: M
authors.lastname: Grzybek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification* / Q000175:diagnosis / Q000378:metabolism*; D008055:Lipids / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D008055:Lipids