Quantitative Analysis of Wilms’ Tumor Gene 1(WT1) Expression in Acute Lymphoblastic Leukemia (ALL) of Adults Reveals Lower WT1 Levels Than in Acute Myeloid Leukemias (AML) and Varying Expression Levels between Individual Patients among Different ALL Subgroups.

Background: Overexpression of the embryonic transcription factor WT1 is common in human acute leukemias. Therefore WT1 became an interesting target mainly for immunotherapeutic approaches in AML. In previously published data from qualitative PCR analysis the frequency of WT1 overexpression in ALL is lower than in AML. But so far only limited data from quantitative analysis of WT1 expression in ALL are available.

Methods: In the present study we analysed bone marrow or blood samples of 238 adult ALL patients at diagnosis for the expression levels of WT1 by real-time RT - PCR (LightCycler). All patients were treated in the German Multicenter Study for the Treatment of ALL (GMALL 07/2003). Only samples containing at least 60 % blasts were used for analysis. Expression levels were compared to previously published data of WT1 expression levels in AML samples.

Results: WT1 expression was found in 219 out of 238 ALL samples (92 %). Compared to AML WT1 expression levels in ALL were significantly lower. There were no differences between the various ALL immuno phenotypes of the B or T lineage, but lymphoblasts with a coexpression of myeloid markers had significantly higher WT1 expression levels than those without a coexpression of myeloid markers. Surprisingly, patients who were bcr-abl negative had significantly higher WT1 expression levels than bcr-abl positive patients.

Conclusions: Using quantitative RT-PCR technology WT1 expression can be found in most ALL cases. There are usually less intense expression patterns compared to AML and expression varies among different ALL subgroups. Thus WT1 has promise to be an interesting target also in ALL therapy but in a more individually determined fashion. The relation of WT1 expression level and treatment outcome is currently being analysed.