Surfaceome interrogation using an RNA-seq approach highlights leukemia initiating cell biomarkers in an LMO2 T cell transgenic model

Research output: Contribution to journalArticle

Authors

  • Helio Pais
  • Katia Ruggero
  • Jing Zhang
  • Osama Al-Assar
  • Nicolas Bery
  • Ravneet Bhuller
  • Cristina Mecucci
  • Ami Miller
  • Terence H. Rabbitts

External organisations

  • Trivago GmbH
  • 199
  • Weatherall Institute of Molecular Medicine
  • Wellcome Trust Centre for Human Genetics
  • Institute of Cancer and Genomic Sciences
  • University Hospital A.O.

Abstract

The surfaceome is critical because surface proteins provide a gateway for internal signals and transfer of molecules into cells, and surfaceome differences can influence therapy response. We have used a surfaceome analysis method, based on comparing RNA-seq data between normal and abnormal cells (Surfaceome DataBase Mining or Surfaceome DBM), to identify sets of upregulated cell surface protein mRNAs in an LMO2-mediated T-ALL mouse model and corroborated by protein detection using antibodies. In this model the leukemia initiating cells (LICs) comprise pre-leukaemic, differentiation inhibited thymocytes allowing us to provide a profile of the LIC surfaceome in which GPR56, CD53 and CD59a are co-expressed with CD25. Implementation of cell surface interaction assays demonstrates fluid interaction of surface proteins and CD25 is only internalized when co-localized with other proteins. The Surfaceome DBM approach to analyse cancer cell surfaceomes is a way to find targetable surface biomarkers for clinical conditions where RNA-seq data from normal and abnormal cell are available.

Details

Original languageEnglish
Article number5760
JournalScientific Reports
Volume9
Issue number1
Publication statusPublished - 8 Apr 2019

ASJC Scopus subject areas