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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

High CD34 surface expression in BCP-ALL predicts poor induction therapy response and is associated with altered expression of genes related to cell migration and adhesion

Author

  • Signe Modvig
  • Rasmus Wernersson
  • Nina Friesgaard Øbro
  • Lars Rønn Olsen
  • Claus Christensen
  • Susanne Rosthøj
  • Matilda Degn
  • Gitte Wullf Jürgensen
  • Hans O. Madsen
  • Birgitte Klug Albertsen
  • Peder Skov Wehner
  • Steen Rosthøj
  • Henrik Lilljebjörn
  • Thoas Fioretos
  • Kjeld Schmiegelow
  • Hanne Vibeke Marquart
Show all

Summary, in English

Minimal residual disease (MRD) constitutes the most important prognostic factor in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Flow cytometry is widely used in MRD assessment, yet little is known regarding the effect of different immunophenotypic subsets on outcome. In this study of 200 BCP-ALL patients, we found that a CD34-positive, CD38 dim-positive, nTdT dim-positive immunophenotype on the leukemic blasts was associated with poor induction therapy response and predicted an MRD level at the end of induction therapy (EOI) of ≥ 0.001. CD34 expression was strongly and positively associated with EOI MRD, whereas CD34-negative patients had a low relapse risk. Further, CD34 expression increased from diagnosis to relapse. CD34 is a stemness-associated cell-surface molecule, possibly involved in cell adhesion/migration or survival. Accordingly, genes associated with stemness were overrepresented among the most upregulated genes in CD34-positive leukemias, and protein–protein interaction networks showed an overrepresentation of genes associated with cell migration, cell adhesion, and negative regulation of apoptosis. The present work is the first to demonstrate a CD34-negative immunophenotype as a good prognostic factor in ALL, whereas high CD34 expression is associated with poor therapy response and an altered gene expression profile reminiscent of migrating cancer stem-like cells.

Department/s

  • Division of Clinical Genetics
  • Translational Genomic and Functional Studies of Leukemia
  • LUCC: Lund University Cancer Centre

Publishing year

2022

Language

English

Pages

2015-2030

Publication/Series

Molecular Oncology

Volume

16

Issue

10

Document type

Journal article

Publisher

Elsevier

Topic

  • Cancer and Oncology

Keywords

  • acute lymphoblastic leukemia
  • CD34
  • cell migration
  • immunophenotype
  • prognosis
  • protein–protein interaction networks

Status

Published

Research group

  • Translational Genomic and Functional Studies of Leukemia

ISBN/ISSN/Other

  • ISSN: 1574-7891