小儿急性淋巴细胞白血病p16基因缺失及甲基化的研究

THE HOMOZYGOUS DELETION AND METHYLATION OF P16 GENE IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

为探讨p1 6基因缺失及甲基化在小儿急性淋巴细胞白血病 (ALL)发病中的作用 ,认识p1 6蛋白失活的分子机制。应用差异PCR技术检测 42例初治、1 7例缓解期小儿ALLp1 6基因的纯合缺失及甲基化。结果 42例ALL中p1 6基因纯合缺失率占38.1 % ,T系ALL占 80 % ,显著高于B系ALL2 2 .5 % ,P <0 0 1。 1 7例缓解期ALL均无基因缺失。 9例p1 6基因完整 ,但无蛋白表达的ALL患者 ,无一例发生基因外显子 1的甲基化。结果表明 ,p1 6基因纯合缺失是小儿ALL ,尤其T系ALL最常见的基因缺陷 ,是p1 6蛋白失活的主要分子机制。基因甲基化与p1 6蛋白失活可能无关。

Objective: To explore the effect of homozygous deletion and methylation of p16 gene on the pathogenesis of ALL and molecular mechanism of p16 protein inactivation. Methods: Differential PCR was applied to examine the homozygous deletion of p16 gene in 42 childhood ALL at present, 17 at complete remission. The methylation of p16 gene was also detected in 9 cases having intact p16 gene but no p16 expression. Results: The homozygous deletion of p16 gene was found in 16 out of 42 ALL (38.1%) and occurred extremely frequently in T-lineage ALL (80%) comparing with B-lineage ALL (20.5%), P<0.01. 17 ALL at complete remission had no p16 gene deletion. The methylation of exon 1 of p16 gene was not found in 9 analyzed cases. Conclusion: The homozygous deletion of p16 gene is the most common gene abnormalities so far detected in ALL, especially in T-ALL, and is also an important mechanism of p16 inactivation. The loss of expression of p16 protein is not due to methylation which silence transcription of p16 gene.