TY - JOUR
T1 - 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
AU - Modvig, Signe
AU - Wernersson, Rasmus
AU - Øbro, Nina Friesgaard
AU - Olsen, Lars Rønn
AU - Christensen, Claus
AU - Rosthøj, Susanne
AU - Degn, Matilda
AU - Jürgensen, Gitte Wullf
AU - Madsen, Hans O.
AU - Albertsen, Birgitte Klug
AU - Wehner, Peder Skov
AU - Rosthøj, Steen
AU - Lilljebjörn, Henrik
AU - Fioretos, Thoas
AU - Schmiegelow, Kjeld
AU - Marquart, Hanne Vibeke
PY - 2022
Y1 - 2022
N2 - 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 amongst the most upregulated genes in CD34 positive leukemias, and protein-protein interaction (PPI) 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 associates with poor therapy response and an altered gene expression profile reminiscent of migrating cancer stem-like cells.
AB - 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 amongst the most upregulated genes in CD34 positive leukemias, and protein-protein interaction (PPI) 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 associates with poor therapy response and an altered gene expression profile reminiscent of migrating cancer stem-like cells.
KW - Acute lymphoblastic leukaemia
KW - CD34
KW - Cell migration
KW - Immunophenotype
KW - Prognosis
KW - Protein-protein interaction networks
U2 - 10.1002/1878-0261.13207
DO - 10.1002/1878-0261.13207
M3 - Journal article
C2 - 35271751
SN - 1574-7891
VL - 16
SP - 2015
EP - 2030
JO - Molecular Oncology
JF - Molecular Oncology
IS - 10
ER -