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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

Modvig, Signe ; Wernersson, Rasmus ; Øbro, Nina Friesgaard ; Olsen, Lars Rønn ; Christensen, Claus ; Rosthøj, Susanne ; Degn, Matilda ; Jürgensen, Gitte Wullf ; Madsen, Hans O. and Albertsen, Birgitte Klug , et al. (2022) In Molecular Oncology 16(10). p.2015-2030
Abstract

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... (More)

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.

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organization
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type
Contribution to journal
publication status
published
subject
keywords
acute lymphoblastic leukemia, CD34, cell migration, immunophenotype, prognosis, protein–protein interaction networks
in
Molecular Oncology
volume
16
issue
10
pages
2015 - 2030
publisher
Elsevier
external identifiers
  • scopus:85127563002
  • pmid:35271751
ISSN
1574-7891
DOI
10.1002/1878-0261.13207
language
English
LU publication?
yes
id
80a85686-3451-40f8-97dd-34d336f4c90c
date added to LUP
2022-06-07 14:31:08
date last changed
2024-06-13 09:39:17
@article{80a85686-3451-40f8-97dd-34d336f4c90c,
  abstract     = {{<p>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.</p>}},
  author       = {{Modvig, Signe and Wernersson, Rasmus and Øbro, Nina Friesgaard and Olsen, Lars Rønn and Christensen, Claus and Rosthøj, Susanne and Degn, Matilda and Jürgensen, Gitte Wullf and Madsen, Hans O. and Albertsen, Birgitte Klug and Wehner, Peder Skov and Rosthøj, Steen and Lilljebjörn, Henrik and Fioretos, Thoas and Schmiegelow, Kjeld and Marquart, Hanne Vibeke}},
  issn         = {{1574-7891}},
  keywords     = {{acute lymphoblastic leukemia; CD34; cell migration; immunophenotype; prognosis; protein–protein interaction networks}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{2015--2030}},
  publisher    = {{Elsevier}},
  series       = {{Molecular Oncology}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1002/1878-0261.13207}},
  doi          = {{10.1002/1878-0261.13207}},
  volume       = {{16}},
  year         = {{2022}},
}