Metabolically distinct subpopulations of a secondary AML cell line are associated with differences in stemness and drug response

In recent years fatty acid metabolism has gained greater attention in haematological cancers, such as myeloid dysplastic syndrome (MDS) and secondary acute myeloid leukaemia (sAML), and has been implicated in increased proliferation and drug resistance. We have characterised two populations of FACS-sorted MDS/sAML cells - SKK-1LOW and SKK-1HIGH - that retain distinct fatty acid uptake phenotypes that are stable over time. Transcriptomic analysis of SKK-1LOW and SKK-1HIGH confirmed differentially expressed genes. Gene ontology analysis revealed gene expression differences principally in fatty acid transport genes and receptor tyrosine kinases, of which KIT was associated with low fatty acid uptake. SKK-1LOW resembled a leukaemic stem cell sub-population on the level of its immunophenotype and exhibited greater resistance to the hypomethylating agent, azacitadine. Overall, this study sheds new light on the relatively under-characterised SKK-1 cell line, which may be useful for the study of MDS-to-sAML transformation. Characterisation of an MDS/sAML cell line in the context of metabolism and immunophenotyping.