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Measurable residual disease monitoring using Wilms tumor gene 1 expression in childhood acute myeloid leukemia based on child-specific reference values

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  • Kristian Løvvik Juul-Dam
  • Charlotte Guldborg Nyvold
  • Helen Vålerhaugen
  • Bernward Zeller
  • Birgitte Lausen
  • Henrik Hasle
  • Hans Beier Ommen
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BACKGROUND: Measurable/minimal residual disease (MRD) monitoring can predict imminent hematological relapse in acute myeloid leukemia (AML). The majority of childhood AML patients do not harbor fusion genes or mutations applicable as MRD markers and overexpression of Wilms tumor gene 1 (WT1) may constitute a useful monitoring target. However, age-specific reference values in healthy hematopoiesis and standardization of WT1 assessment are prerequisites for clinical utility.

PROCEDURE: We investigated WT1 expression across age in hematologically healthy controls (n = 109), during suspected infection (n = 90) and bone marrow (BM) regeneration (n = 13). WT1 expression in AML at diagnosis (n = 91) and during follow-up (n = 30) was compared with age-specific reference values.

RESULTS: WT1 expression correlated with age and showed higher levels in both BM and peripheral blood (PB) in children compared with adults (P < 0.001 and P = 0.01). WT1 expression from healthy hematopoiesis was lower in PB compared with BM (WT1BM /WT1PB = 8.6, 95% CI: 5.3-13.7) and not influenced by infection nor BM regeneration. At AML diagnosis, 66% had more than 20-fold WT1 overexpression in PB or BM (PB 74%; BM 45%). WT1 was quantified in 279 PB samples during follow-up. All 11 patients with PB sampling within 4 months of disease recurrence displayed WT1 overexpression by a median of 1.9 months (range, 0.7-9.7) before hematological relapse.

CONCLUSIONS: This study defines child-specific reference values for WT1 expression in healthy hematopoiesis and demonstrates that WT1 expression in PB is a useful post-treatment monitoring tool in childhood AML. Based on these observations, we propose definitions for childhood AML molecular relapse using WT1 overexpression.

Original languageEnglish
JournalPediatric Blood & Cancer
Volume66
Issue number6
Pages (from-to)e27671
ISSN1545-5009
DOIs
Publication statusPublished - 2019

    Research areas

  • Adolescent, Adult, Biomarkers, Tumor/blood, Bone Marrow/metabolism, Case-Control Studies, Child, Child, Preschool, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Infant, Leukemia, Myeloid, Acute/metabolism, Male, Neoplasm Recurrence, Local/metabolism, Neoplasm, Residual/metabolism, Prognosis, Reference Values, WT1 Proteins/blood

ID: 59088381