Thoas Fioretos
Research team manager
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
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