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Quantitative proteomics reveals specific metabolic features of acute myeloid leukemia stem cells

Item Type:Article
Title:Quantitative proteomics reveals specific metabolic features of acute myeloid leukemia stem cells
Creators Name:Raffel, S. and Klimmeck, D. and Falcone, M. and Demir, A. and Pouya, A. and Zeisberger, P. and Lutz, C. and Tinelli, M. and Bischel, O. and Bullinger, L. and Thiede, C. and Flörcken, A. and Westermann, J. and Ehninger, G. and Ho, A.D. and Müller-Tidow, C. and Gu, Z. and Herrmann, C. and Krijgsveld, J. and Trumpp, A. and Hansson, J.
Abstract:Acute myeloid leukemia is characterized by the accumulation of clonal myeloid blast cells unable to differentiate into mature leukocytes. Chemotherapy induces remission in the majority of patients, but relapse rates are high and lead to poor clinical outcomes. Because this is primarily caused by chemotherapy-resistant leukemic stem cells (LSCs), it is essential to eradicate LSCs to improve patient survival. LSCs have predominantly been studied at the transcript level, thus information about posttranscriptionally regulated genes and associated networks is lacking. Here, we extend our previous report on LSC proteomes to healthy age-matched hematopoietic stem and progenitor cells (HSPCs) and correlate the proteomes to the corresponding transcriptomes. By comparing LSCs to leukemic blasts and healthy HSPCs, we validate candidate LSC markers and highlight novel and potentially targetable proteins that are absent or only lowly expressed in HSPCs. In addition, our data provide strong evidence that LSCs harbor a characteristic energy metabolism, adhesion molecule composition, as well as RNA-processing properties. Furthermore, correlating proteome and transcript data of the same individual samples highlights the strength of proteome analyses, which are particularly potent in detecting alterations in metabolic pathways. In summary, our study provides a comprehensive proteomic and transcriptomic characterization of functionally validated LSCs, blasts, and healthy HSPCs, representing a valuable resource helping to design LSC-directed therapies.
Keywords:Acute Leukemia Myeloid, Energy Metabolism, Leukemic Gene Expression Regulation, Neoplastic Stem Cells, Proteome, Proteomics, Transcriptome, Animals, Mice
Publisher:American Society of Hematology
Page Range:1507-1519
Date:24 September 2020
Official Publication:https://doi.org/10.1182/blood.2019003654
PubMed:View item in PubMed

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