Prognostic significance of molecular detection of minimal residual disease in childhood acute lymphoblastic leukemia

儿童急性淋巴细胞白血病微小残留病分子检测的预后意义

• 批准号: 08670875
• 负责人: HORIBE Keizo
• 金额: $ 1.41万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670875/
• 关键词: Acute lymphoblastic leukemia; Minimal residual disease; Polymerase chain reaction; Immunoglobulin heavy chain; TEL-AML1; BCR-ABL; E2A-PBX1; Prognostic factor; CDRIII; t(12;21); t(1;19); t(9;22)

Detection and clinical assessment of minimal residual disease (MRD) of acute lymphoblastic leukemia (ALL) were performed for 50 children with ALL diagnosed and treated between 1987 to 1997 in Nagoya University Hospital and its affiliated hospitals. E2A-PBX1, BCR-ABL and TEL-AML1 were detected by reverse transcription polymerase chain reaction (RT-PCR) method for leukemia with t (l ; 19), t (9 ; 22) or t (12 ; 21). In 26 cases of leukemia without detectable specific traslocation MRD was assessed by PCR using unique sequence of complementality determining region III of immunoglobulin heavy chain (IgH CDR III).Bone marrow samples at 1 to 3 months after starting chemotherapy were available in 19 patients with specific fusion gene. Two of 16 patients negative for the MRD at that time relapsed later, while all the 3 patients positive for the MRD at that time relapsed later. Bone marrow samples at 1 to 3 months after starting chemotherapy were analyzed in 23 patients using specific probe for IgH CDR III.Five of 19 patients negative for the MRD at that time relapsed later, while all the 3 patients positive for the MRD at that time relapsed later. Combining these data, prognosis for patients with positive MRD at 1 to 3 months after starting chemotherapy was significantly worse than that for patients with negative MRD at that time.Now we are going to collect the cases with uniform chemotherapy to analyze the MRD and to establish its usefulness for stratifying the treatment for childhood ALL in Japan.

对1987年至1997年间在名古屋大学医院及其附属医院诊断和治疗的50例急性淋巴细胞白血病（ALL）患儿进行了微小残留病（MRD）检测和临床评估。采用逆转录聚合酶链式反应(RT-PCR)法检测t(1；19)、t(9；22)或t(12；21)白血病的E2A-PBX1、BCR-ABL和TEL-AML1。在 26 例没有可检测到的特异性易位的白血病病例中，使用免疫球蛋白重链互补性决定区 III (IgH CDR III) 的独特序列，通过 PCR 评估了 MRD。 19 例具有特异性易位的患者在开始化疗后 1 至 3 个月时获得了骨髓样本。融合基因。当时 16 名 MRD 阴性患者中有 2 名后来复发，而当时 MRD 阳性的 3 名患者全部后来复发。使用 IgH CDR III 特异性探针对 23 名患者开始化疗后 1 至 3 个月的骨髓样本进行分析。当时 MRD 阴性的 19 名患者中有 5 名后来复发，而当时 MRD 全部阳性的 3 名患者后来又复发了。综合这些数据，开始化疗后1~3个月MRD阳性的患者预后明显差于当时MRD阴性的患者。现在我们将收集统一化疗的病例进行MRD分析，建立它对于日本儿童 ALL 的分层治疗很有用。