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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
Author(s) -
Løvvik JuulDam Kristian,
Guldborg Nyvold Charlotte,
Vålerhaugen Helen,
Zeller Bernward,
Lausen Birgitte,
Hasle Henrik,
Beier Ommen Hans
Publication year - 2019
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.27671
Subject(s) - wilms' tumor , medicine , minimal residual disease , haematopoiesis , myeloid leukemia , bone marrow , myeloid , oncology , leukemia , stem cell , pathology , biology , genetics
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 ( WT1 BM / WT1 PB = 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.