Heyman M, Grandér D, Bröndum-Nielsen K, Liu Y, Söderhäll S, Einhorn S
Division of Experimental Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Int J Cancer. 1993 Jul 9;54(5):748-53. doi: 10.1002/ijc.2910540507.
A restriction fragment length polymorphism (RFLP) analysis of the alpha- and beta-interferon (IFN) genes was performed in malignant cells from 52 patients with acute lymphocytic leukemia (ALL). Normal cell DNA was available for comparison in 23 of the patients. Ten patients were found to have gross alterations of their alpha- and beta-IFN genes. Leukemic cells from 2 ALL patients showed a complete loss of alpha- and beta-IFN genes. Seven patients had a hemizygous loss of one of the alpha- and beta-IFN alleles, as shown by RFLP analysis and/or loss of signal intensity. In one other patient the malignant clone was reduced to homozygosity with regard to the alpha- and beta-IFN genes, without loss of signal intensity. In patients without hemizygous deletions, the overall incidence of complete homozygosity for the alpha- and beta polymorphisms was higher than expected. Analysis of the data indicates that the total frequency of ALL clones with gross alterations of the IFN-loci is around 30%. A 9p24 probe detected hemizygous deletions in 2 cases of IFN gene deletions. In the other tested cases the deletions were interstitial. No deletions of 9p24 were detected in patients without allelic losses of IFN genes. In 5 cases of allelic IFN gene deletions, DNA from parents was available for comparison. In 4 cases the deleted allele was derived from the mother, whereas in the fifth it originated from the father. Pediatric ALL patients with IFN-gene deletions or homozygosity for all polymorphisms in the IFN-loci had a significantly worse prognosis than heterozygotes. We conclude that deletion of alpha- and beta-IFN genes is a relatively common event in ALL and that RFLP analysis of the IFN genes may provide additional prognostic information in childhood ALL. Whether or not the IFNs act as tumor-suppressor genes in this disease is not yet known.
对52例急性淋巴细胞白血病（ALL）患者的恶性细胞进行了α和β干扰素（IFN）基因的限制性片段长度多态性（RFLP）分析。23例患者有正常细胞DNA可供比较。发现10例患者的α和β-IFN基因有明显改变。2例ALL患者的白血病细胞显示α和β-IFN基因完全缺失。7例患者经RFLP分析和/或信号强度丧失显示α和β-IFN等位基因之一半合子缺失。另一例患者的恶性克隆在α和β-IFN基因方面纯合化，但信号强度未丧失。在没有半合子缺失的患者中，α和β多态性完全纯合的总体发生率高于预期。数据分析表明，IFN基因座有明显改变的ALL克隆的总频率约为30%。一个9p24探针在2例IFN基因缺失中检测到半合子缺失。在其他检测病例中，缺失为间质型。在没有IFN基因等位基因缺失的患者中未检测到9p24缺失。在5例等位基因IFN基因缺失中，有父母的DNA可供比较。4例中缺失的等位基因来自母亲，而第5例来自父亲。IFN基因缺失或IFN基因座所有多态性均为纯合子的小儿ALL患者的预后明显比杂合子差。我们得出结论，α和β-IFN基因缺失在ALL中是相对常见的事件，IFN基因的RFLP分析可能为儿童ALL提供额外的预后信息。在这种疾病中IFN是否作为肿瘤抑制基因尚不清楚。
