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Proteomes 2018, 6(1), 11; https://doi.org/10.3390/proteomes6010011

Pilot Study on Mass Spectrometry–Based Analysis of the Proteome of CD34+CD123+ Progenitor Cells for the Identification of Potential Targets for Immunotherapy in Acute Myeloid Leukemia

1
Department of Molecular Systems Biology, Helmholtz-Centre for Environmental Research—UFZ, 04318 Leipzig, Germany
2
Department of Medicine I, University Hospital of Dresden, 01307 Dresden, Germany
3
Center for Regenerative Therapies Dresden, TU Dresden, 01307 Dresden, Germany
4
German Cancer Consortium (DKTK), 01307 Dresden, Germany
5
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
6
National Center for Tumor Diseases, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany
7
DKMS German Bone Marrow Donor Center, Clinical Trials Unit, 01309 Dresden, Germany
8
Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, 04103 Leipzig, Germany
*
Author to whom correspondence should be addressed.
Received: 17 December 2017 / Revised: 3 February 2018 / Accepted: 8 February 2018 / Published: 12 February 2018
(This article belongs to the Special Issue The Proteome in Stem Cell Transplantation)
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Abstract

Targeting of leukemic stem cells with specific immunotherapy would be an ideal approach for the treatment of myeloid malignancies, but suitable epitopes are unknown. The comparative proteome-level characterization of hematopoietic stem and progenitor cells from healthy stem cell donors and patients with acute myeloid leukemia has the potential to reveal differentially expressed proteins which can be used as surface-markers or as proxies for affected molecular pathways. We employed mass spectrometry methods to analyze the proteome of the cytosolic and the membrane fraction of CD34 and CD123 co-expressing FACS-sorted leukemic progenitors from five patients with acute myeloid leukemia. As a reference, CD34+CD123+ normal hematopoietic progenitor cells from five healthy, granulocyte-colony stimulating factor (G-CSF) mobilized stem cell donors were analyzed. In this Tandem Mass Tag (TMT) 10-plex labelling–based approach, 2070 proteins were identified with 171 proteins differentially abundant in one or both cellular compartments. This proof-of-principle-study demonstrates the potential of mass spectrometry to detect differentially expressed proteins in two compartment fractions of the entire proteome of leukemic stem cells, compared to their non-malignant counterparts. This may contribute to future immunotherapeutic target discoveries and individualized AML patient characterization. View Full-Text
Keywords: hematopoietic stem/progenitor cells; acute myeloid leukemia; leukemic stem/progenitor cells; proteome hematopoietic stem/progenitor cells; acute myeloid leukemia; leukemic stem/progenitor cells; proteome
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Schmidt, J.R.; Rücker-Braun, E.; Heidrich, K.; von Bonin, M.; Stölzel, F.; Thiede, C.; Middeke, J.M.; Ehninger, G.; Bornhäuser, M.; Schetelig, J.; Schubert, K.; von Bergen, M.; Heidenreich, F. Pilot Study on Mass Spectrometry–Based Analysis of the Proteome of CD34+CD123+ Progenitor Cells for the Identification of Potential Targets for Immunotherapy in Acute Myeloid Leukemia. Proteomes 2018, 6, 11.

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