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WT1 as a new prognostic factor and a new marker for the detection of
minimal residual disease in acute leukemia
K Inoue, H Sugiyama, H Ogawa, M Nakagawa, T Yamagami, H Miwa, K Kita, A Hiraoka, T Masaoka and K Nasu
Department of Medicine III, Osaka University Medical School, Japan.
The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene
that plays a key role in the carcinogenesis of Wilms' tumor. Reverse
transcriptase-polymerase chain reaction (RT-PCR) was used to examine
relative levels of WT1 gene expression (defined in K562 cells as 1.00) in
45 patients with acute myelogenous leukemia (AML), 22 with acute
lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23
with chronic myelogenous leukemia (CML), and 24 with non- Hodgkin's
lymphoma. Significant levels of WT1 gene were expressed in all leukemia
patients and for CML the levels increased as the clinical phase progressed.
In striking contrast with acute leukemia, the levels of WT1 gene expression
for NHL were significantly lower or even undetectable. Clear correlation
was observed between the relative levels of WT1 gene expression (< 0.6 v
> or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL).
Patients with less than 0.6 levels had significantly higher rates of
complete remission (CR), disease-free survival, and overall survival than
those with > or = 0.6 levels, whereas CR could not be induced in any of
the 7 patients with acute leukemia having greater than 1.0 levels of WT1
gene expression. The quantitation of the WT1 gene expression made it
possible to detect minimal residual disease (MRD) in acute leukemia
regardless of the presence or absence of tumor-specific DNA markers.
Continuous monitoring of the WT1 mRNA was performed for 9 patients with
acute leukemia. In 4 patients, MRD was detected 2 to 8 months before
clinical relapse became apparent. In 2 other patients, the WT1 mRNA
gradually increased after discontinuation of chemotherapy. No MRD was
detected in the remaining 3 patients with AML who received intensive
induction and consolidation therapy. Simultaneous monitoring of MRD by
RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with
PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected
MRD comparable with that obtained from quantitation of WT1 gene expression.
In a patient with acute promyelocytic leukemia, the limits of leukemic cell
detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic
acid receptor-alpha gene primers were 10(-3) to 10(- 4) and 10(-4) for bone
marrow, and 10(-5) and 10(-4) for peripheral blood, respectively.
Therefore, we conclude that WT1 is a new prognostic factor and a new marker
for the detection of MRD in acute leukemia.
Volume 84,
Issue 9,
pp. 3071-3079,
11/01/1994
Copyright © 1994 by The American Society of Hematology
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K. Inoue, H. Tamaki, H. Oga | |
