title: Leukemia surfaceome analysis reveals new disease-associated features.
abstract: A better description of the leukemia cell surface proteome (surfaceome) is a prerequisite for the development of diagnostic and therapeutic tools. Insights into the complexity of the surfaceome have been limited by the lack of suitable methodologies. We combined a leukemia xenograft model with the discovery-driven chemoproteomic Cell Surface Capture technology to explore the B-cell precursor acute lymphoblastic leukemia (BCP-ALL) surfaceome; 713 cell surface proteins, including 181 CD proteins, were detected through combined analysis of 19 BCP-ALL cases. Diagnostic immunophenotypes were recapitulated in each case, and subtype specific markers were detected. To identify new leukemia-associated markers, we filtered the surfaceome data set against gene expression information from sorted, normal hematopoietic cells. Nine candidate markers (CD18, CD63, CD31, CD97, CD102, CD157, CD217, CD305, and CD317) were validated by flow cytometry in patient samples at diagnosis and during chemotherapy. CD97, CD157, CD63, and CD305 accounted for the most informative differences between normal and malignant cells. The ALL surfaceome constitutes a valuable resource to assist the functional exploration of surface markers in normal and malignant lymphopoiesis. This unbiased approach will also contribute to the development of strategies that rely on complex information for multidimensional flow cytometry data analysis to improve its diagnostic applications.
authors: Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland.
authors: Paulina
authors: P
authors: Mirkowska
authors: Andreas
authors: A
authors: Hofmann
authors: Lukasz
authors: L
authors: Sedek
authors: Lucie
authors: L
authors: Slamova
authors: Ester
authors: E
authors: Mejstrikova
authors: Tomasz
authors: T
authors: Szczepanski
authors: Maike
authors: M
authors: Schmitz
authors: Gunnar
authors: G
authors: Cario
authors: Martin
authors: M
authors: Stanulla
authors: Martin
authors: M
authors: Schrappe
authors: Vincent H J
authors: VH
authors: van der Velden
authors: Beat C
authors: BC
authors: Bornhauser
authors: Bernd
authors: B
authors: Wollscheid
authors: Jean-Pierre
authors: JP
authors: Bourquin
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008565:Membrane Proteins / Q000032:analysis* / Q000378:metabolism; D051379:Mice; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000378:metabolism*; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D020543:Proteome