初诊和复发的急性淋巴细胞白血病P15、P16基因失活的研究

目的：探讨多肿瘤抑制基因（MTS）P15和（或）P16的改变是否可影响急性淋巴细胞白血病（ALL）的病程及其预后。方法：跟踪30例复发的ALL患者在初诊和第1次骨髓复发时的骨髓标本，用PCR法监测P16 exon 1,P16 exon 2,P15 exon 1的缺失；用REP法检测P16 exon 1,P15 exon 1高度甲基化情况。结果：在初诊患者中共有50％（12／30）的患者有（或）P16基因失活，P16缺失的患者有8例，其中7例伴有P15缺失，7例P15甲基化的患者有2例伴P16甲基化。在初诊时，15例无该基因异常的患者，复发期间有11例出现P15和（或）P16异常，占86．7％（26／30），与初诊时48％（12／25）比较，差异有极显著性意义（P＜0．01）。结论：我们认为P15和（或）P16的失活可加快疾病的复发，监测ALL患者的P15和（或）P16失活，可用于预测疾病的病程和预后，初诊和复诊均有异常者为难治性疾病。

Study on inactivation of P15, P16 gene between initial and relapsed acute lymphoblastic leukemia

Objective:Evaluate whether alternation of P16 and/or P15 gene play a significant role of progression and prognosis in acute lymphoblastic leukemia.Method:30 bone marrow samples of acute lymphoblastic leukemia at initial diagnosis and first bone marrow relapse were studied. Homozygous deletion of P16 exon1, P16 exon2, and P15 exon1 were detected by means of PCR. In addition, REP was used to detect hypermethylation of P16 exon1 and P15 exon1.Result:At the initial diagnosis, inactivation of P15 and/or P16 gene were detected in 15 of 30 (50%), 8 cases occurred P16 gene homozygous deletion, in which P15 homozygous deletion were detected in 7 cases. 7 cases occurred P15 gene hypermethylation and among them 2 cases had P16 gene hypermethylation simultaneously. Patients without abnormal P15 and P16 at initial diagnosis, inactivation of P15 and/or P16 have been detected in 11 cases at relapse. At relapse, inactivation of P15 and/or P16 gene were found in 26 of 30 ( 86.7%) cases, compared with the initial diagnosis (48%), there was a significant difference (P< 0.01).Conclusion:It suggested that inactivation of P15 and/or P16 gene accelerate the relapse of disease. The detection of inactivation of P15 and/or P16 gene may be used to predict the progression and prognosis of ALL. These genes inactivation both initial and relapse imply that the treatment is refractory.