급성 백혈병에서 WT1 유전자 발현과 예후와의 상관성
Prognostic Significance of WT1 Gene Expression in Patients with Acute Leukemia
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배경 : WT1 유전자(Wilms' Tumor gene)는 염색체 11p13에위치하는 유전자로, 급성 백혈병에서 발현되고 WT1 유전자의 발현 정도가 예후에 영향을 준다고 보고되고 있다. 저자들은 급성백혈병의 진단 당시 WT1 유전자 발현 정도가 완전관해 및 생존율과 상관관계가 있는지 알아보고 예후를 예측하는 인자로써의유용성을 알아보고자 하였다.방법 :급성 백혈병 환자(AML 39명, ALL 32명)를 대상으로,급성 백혈병에서 WT1유전자 발현과 예후와의 상관성 83진단 당시 골수천자 검체로 WT1 유전자에 대한 nested RT-PCR을 시행하였다. 유전자 발현 정도를 반정량 하기 위하여 동량의 RNA로 -actin에 대하여서도 RT-PCR을 실시하여 -actin에 대한 WT1의 발현 비율을 구하였다. WT1과 -actin 유전자발현의 비율에 따라 1+ (0.75 미만), 2+ (0.75-1.0), 3+ (1.0 초과)로 구분하였다. WT1 유전자 반정량 결과와 임상 양상 및 혈액학적 검사 결과의 상관성을 분석하였다. 결과 :진단 당시 급성 백혈병의 34예(47.9%)에서 WT1 유전자가 발현되었고, 양성을 보인 예 중 1+인 예는 10예(14.1%),2+는 20예(28.2%), 3+는 4예(5.6%)였다. 급성 골수구성 백혈병과 급성 림프구성 백혈병의 WT1 유전자 발현 양성은 각각 18예(46%), 16예(50%)였다. 급성 골수구성 백혈병군에서 WT1유전자 발현 양성인 군의 나이가 음성인군 보다 의미있게 낮았고,관해유도 후 WT1 유전자 발현 양성인 군의 50%, 음성인 군의61.9%에서 완전관해를 얻었다. 급성 림프구성 백혈병군에서는WT1 유전자 발현 양성인 군과 음성인 군의 각 68.8%, 75.0%에서 완전관해를 얻었다. WT1 유전자 발현에 따른 5년 생존율비교에서 양성인 군의 44.1%, 음성인 군의 62.2%가 5년 동안 생존했다. 한 예 외에 전례가 생존한 소아 급성 림프구성 백혈병을제외한 WT1 유전자 발현 정도에 따른 5년 생존율 비교에서 WT1유전자 발현 음성인 군의 생존기간 중앙값은 709일, 1+ 또는 2+인 군의 생존기간 중앙값은 310일, 3+의 높은 양성 정도를 보였던 군의 중앙값은 294일로 양성 정도가 증가할수록 불량한 예후를 보였다. 결론 : 급성 백혈병의 약 반에서 WT1 유전자가 발현됨을 알수 있었고, WT1 유전자 발현 양성인 군의 완전관해율이 음성인군보다 낮은 경향을 보였고, 양성정도가 증가할수록 낮은 생존율을 나타내는 경향을 보여, 급성 백혈병 환자의 예후에 대한 지표로 이용할 수 있을 것으로 생각된다.
Abstract
Background : The Wilms’ tumor gene (WT1) is located on chromosome 11p13. Several authors have shown that the expression of WT1 gene is associated with prognosis of acute leukemia. It was the aim of this study to investigate the relationship between WT1 positivity and the response to treatment in terms of rate of complete remissions (CR), and survival and to evaluate the prognostic value of WT1 expression in patients with acute leukemia. Methods : We examined the presence of WT1 specific mRNA in bone marrow samples of 71 patients with acute leukemia at diagnosis (AML 39, ALL 32) by nested RT-PCR. The integrity and the amount of RNA were analyzed by amplification of the -actin gene as an internal control. The relative ratio of WT1 gene expression/ -actin was calculated and classified as not amplified (0), weakly amplified (1+), moderately amplified (2+), or strongly amplified (3+). Results : Thirty-four (47.9%) of the patients with acute leukemia at diagnosis were WT1 PCR positive. Among the WT1 positive patients, 10 patients (14.1%) showed 1+, 20 patients (28.2%) 2+, and 4 patients (5.6%) 3+. The patients with WT1 mRNA expression were younger than those without it in AML. There was a tendency of a higher CR rates in WT1 negative patients than in WT1 positive ones (AML 61.9% vs. 50%, ALL 75.0% vs. 68.8%). The probability of 5 year survival was 62.2% for WT1 negative group and 44.1% for WT1 positive group in all patients. The median survival days according to levels of WT1 expression was 709 days for negative group, 310 days for 1+ or 2+ groups and 294 days for 3+ group. Conclusions : The present data suggest a clinical relevance of WT1 expression for the achievement of CR and long term survival in acute leukemia. Analysis of WT1 expression with bone marrow aspirates at the diagnosis of acute leukemia may be useful to predict prognosis.
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