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使用滤纸片分析伊拉克儿童急性髓系白血病的 I 类和 II 类畸变。

Analysis of class I and II aberrations in Iraqi childhood acute myeloid leukemia using filter paper cards.

机构信息

Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Nagano, Japan.

出版信息

Ann Hematol. 2014 Jun;93(6):949-55. doi: 10.1007/s00277-014-2007-2. Epub 2014 Jan 25.

Abstract

The lack of molecular diagnosis in the field of cancer in Iraq has motivated us to perform a genetic analysis of pediatric acute myelogenous leukemia (AML), including class I and II aberrations. Peripheral blood or bone marrow cells were collected from 134 AML children aged ≤15 years. Flinders Technology Associates (FTA) filter paper cards were used to transfer dried blood samples from five Iraqi hospitals to Japan. DNA sequencing was performed to identify class I mutations. Nested RT-PCR was used to detect class II aberrations, except that MLL rearrangement was detected according to long distance inverse-PCR. NPM1 and FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations were analyzed by GeneScan using DNA template. Among 134 Iraqi pediatric AML samples, the most prevalent FAB subtype was M2 (33.6 %) followed by M3 (17.9 %). Class I mutations: 20 (14.9 %), 8 (6.0 %), and 8 (6.0 %) patients had FLT3-ITD, FLT3-TKD, and KIT mutations, respectively. Class II mutations: 24 (17.9 %), 19 (14.2 %), and 9 (6.7 %) children had PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 transcripts, respectively. MLL rearrangements were detected in 25 (18.7 %) patients. NPM1 mutation was detected in seven (5.2 %) cases. Collectively, approximately 30 % of AML children were proved to carry favorable prognostic genetic abnormalities, whereas approximately 10 % had high FLT3-ITD allelic burden and needed a special treatment plan including allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) was frequent among Iraqi pediatric AML. It is likely that molecular diagnosis using FTA cards in underdeveloped countries could guide doctors towards an appropriate treatment strategy.

摘要

伊拉克癌症领域缺乏分子诊断技术,这促使我们对儿科急性髓细胞白血病(AML)进行了基因分析,包括 I 类和 II 类异常。采集了 134 名年龄≤15 岁的 AML 儿童的外周血或骨髓细胞。使用 Flinders Technology Associates (FTA) 滤纸卡将来自伊拉克五家医院的干燥血样转移到日本。进行 DNA 测序以鉴定 I 类突变。巢式 RT-PCR 用于检测 II 类异常,但 MLL 重排根据长距离反向-PCR 进行检测。使用 DNA 模板通过 GeneScan 分析 NPM1 和 FMS 样酪氨酸激酶 3 内部串联重复(FLT3-ITD)突变。在 134 例伊拉克儿科 AML 样本中,最常见的 FAB 亚型是 M2(33.6%),其次是 M3(17.9%)。I 类突变:分别有 20(14.9%)、8(6.0%)和 8(6.0%)例患者存在 FLT3-ITD、FLT3-TKD 和 KIT 突变。II 类突变:分别有 24(17.9%)、19(14.2%)和 9(6.7%)例儿童存在 PML-RARA、RUNX1-RUNX1T1 和 CBFB-MYH11 转录本。25(18.7%)例患者检测到 MLL 重排。7(5.2%)例患者检测到 NPM1 突变。总体而言,约 30%的 AML 患儿被证实携带有利的预后遗传异常,而约 10%的患儿具有高 FLT3-ITD 等位基因负荷,需要包括异基因造血干细胞移植在内的特殊治疗方案。急性早幼粒细胞白血病(APL)在伊拉克儿科 AML 中较为常见。在欠发达国家使用 FTA 卡进行分子诊断可能有助于医生制定适当的治疗策略。

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