Expression of WT1 Gene in Childhood Acute Leukemia

Choi, Hyoung Soo; Koh, Sang Hyeok; Yoo, Keon Hee; Jang, Pil Sang; Shin, Hee Young; Ahn, Hyo Seop

Abstract

PURPOSE: Recently Wilms tumor gene (WT1) transcripts have been detected in leukemia regardless of the disease subtype and the specific DNA markers suggesting that WT1 gene might be a useful panleukemic marker for monitoring minimal residual disease (MRD). This study was performed to investigate the expression of WT1 gene by a quantitative methods and to find the prognostic value of WT1 gene in childhood acute leukemia.
METHODS
From the mononuclear cells isolated from bone marrow aspirates and peripheral bloods of 22 childhood acute and chronic leukemia patients, mRNA were extracted for the reverse transcriptase-polymerase chain reactions (RT-PCR). Relative levels of WT1 gene expression was calculated by using the value in K562 cell line to be 1.00 as a positive control.
RESULTS
The sensitivity of detection of MRD with WT1 primers was 10 4 and comparable to that of bcr/abl expression in K562 cells and a patient with CML in blast crisis. WT1 gene expression was detected in 17 of 22 (77%) patients; 9/10 of acute lymphoblastic leukemia (ALL), 6/10 acute myelogenous leukemia (AML), 1 acute mixed lineage leukemia (AMLL) and 1 chronic myelogenous leukemia (CML) in blast crisis. In 4 AML patients who received autologous peripheral blood stem cell transplantation (PBSCT), two patients relapsed after reappearance of WT1 gene expression in bone marrow aspirates and the remaining two were in complete remission without expression of WT1 gene.
CONCLUSION
These results show that WT1 gene expression is frequently noted in childhood acute leukemia and can be a useful sensitive marker for the detection of MRD comparable to bcr/abl transcripts. WT1 gene can be used as a panleukemic marker for the MRD monitoring for the evaluation of the remission status and in predicting early relapse in children with acute leukemia in the molecular levels. It may also be a useful tool for the detection of leukemic cell contamination in the process of peripheral blood stem cell transplantation.