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

N1 - Publisher Copyright: © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

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 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.

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 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.

KW - acute lymphoblastic leukemia

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

AN - SCOPUS:85127563002

VL - 16

SP - 2015

EP - 2030

JO - Molecular Oncology

JF - Molecular Oncology

SN - 1574-7891

IS - 10

ER -