title: A proteomics and transcriptomics approach to identify leukemic stem cell (LSC) markers.
abstract: Interactions between hematopoietic stem cells and their niche are mediated by proteins within the plasma membrane (PM) and changes in these interactions might alter hematopoietic stem cell fate and ultimately result in acute myeloid leukemia (AML). Here, using nano-LC/MS/MS, we set out to analyze the PM profile of two leukemia patient samples. We identified 867 and 610 unique CD34(+) PM (-associated) proteins in these AML samples respectively, including previously described proteins such as CD47, CD44, CD135, CD96, and ITGA5, but also novel ones like CD82, CD97, CD99, PTH2R, ESAM, MET, and ITGA6. Further validation by flow cytometry and functional studies indicated that long-term self-renewing leukemic stem cells reside within the CD34(+)/ITGA6(+) fraction, at least in a subset of AML cases. Furthermore, we combined proteomics with transcriptomics approaches using a large panel of AML CD34(+) (n = 60) and normal bone marrow CD34(+) (n = 40) samples. Thus, we identified eight subgroups of AML patients based on their specific PM expression profile. GSEA analysis revealed that these eight subgroups are enriched for specific cellular processes.
authors.affiliation: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, The Netherlands.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonardi
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Fusetti
authors.forename: Patrick
authors.initials: P
authors.lastname: Deelen
authors.forename: Djoke
authors.initials: D
authors.lastname: van Gosliga
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Jan Jacob
authors.initials: JJ
authors.lastname: Schuringa
mesh_terms: D000208:Acute Disease; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002853:Chromatography, Liquid; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism*; D036103:Nanotechnology / Q000379:methods; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D025341:Principal Component Analysis; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D039503:Integrin alpha6; D020543:Proteome