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.
Highlights
Acute Myeloid Leukemia (AML) is a clonal bone marrow disorder resulting from diverse phenotypic and genetic alterations in the differentiation of hematopoietic stem cells and causing excessive proliferation and accumulation of abnormal immature leukemic neoplastic cells, called blasts[1,2,3,4]
We focused on three subsets of patients with specific clinical and biological AML characteristics: translocation t(8;21), inversion inv16 and patients with normal karyotype (AML-nk)
A two-dimensional score plot was generated (Fig 1), revealing t(8;21) samples clearly separated from inv16 and AML-nk patient samples—the latter clustered together
Summary
Acute Myeloid Leukemia (AML) is a clonal bone marrow disorder resulting from diverse phenotypic and genetic alterations in the differentiation of hematopoietic stem cells and causing excessive proliferation and accumulation of abnormal immature leukemic neoplastic cells, called blasts[1,2,3,4]. Most efforts towards molecular characterization of AML have focused on genome, transcriptome or proteome changes [7,8,9,10,11,12] while evidence is growing that neoplastic pathogenesis and progression involve, and might even be accelerated by, changes in cellular lipidomes[13,14,15,16,17,18,19]. We declare that the commercial affiliation “Lipotype GmBH” does not alter our adherence to all PLOS ONE policies on sharing data and materials
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