Technical aspects and clinical applications of measuring BCR-ABL1 transcripts number in chronic myeloid leukemia
Technical aspects and clinical applications of measuring BCR-ABL1 transcripts number in chronic myeloid leukemia
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DOI：
10.1002/ajh.21457
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发表时间：
2009-08-01
影响因子：
12.8
通讯作者：
Marin, David
中科院分区：
文献类型：
--
作者：
Foroni, Letizia;Gerrard, Gareth;Marin, David
慢性粒细胞白血病 (CIVIL) 是一种骨髓增殖性疾病，其特征为三相临床病程、终末分化骨髓细胞的形态扩张以及 BCR-ABL1 融合基因的存在，这是 CIVIL 的标志。融合基因通常（但并非总是）与费城染色体相关，这是 22 号染色体和 9 号染色体之间遗传物质相互交换的结果，从而导致产生激活的 BCR-ABL1 基因和癌蛋白。 BCR 基因中的断点通常出现在外显子 e13 或 e14 (M-BCR) 下游，较少出现在外显子 e1 和 e2 (m-BCR) 下游。不到 1% 的病例在外显子 6 或 8（“变异融合基因”）或外显子 19 (mu-BCR) 下游携带断点。 ABL1 基因簇位于外显子 a2 上游（或不到 5% 的 CIVIL 患者中的外显子 a3）。常规细胞遗传学、荧光原位杂交和 BCR-ABL1 融合基因的分子检测是 CIVIL 诊断和监测的关键研究。使用酪氨酸激酶抑制剂的治疗彻底改变了 CIVIL 的治疗，超过 85% 的患者在 12-18 个月内观察到血液学和细胞遗传学反应。然而，15% 至 20% 的患者可能会发展至急变期。使用分子测试测量低水平或“最小”残留疾病正在成为测量治疗反应的金标准方法，因为与其他常规技术相比，其灵敏度更高。分子监测的技术方面和临床应用将是本文的主要焦点。是。 J.赫马托尔。 84:517-522, 2009。(C) 2009 Wiley-Liss, Inc.
Chronic myeloid leukemia (CIVIL) is a myeloproliferative disorder characterized by a triphasic clinical course, the morphologic expansion of a terminally differentiated myelold cell and the presence of the BCR-ABL1 fusion gene, the hallmark of CIVIL. The fusion gene is usually, but not always, associated with a Philadelphia chromosome, the result of a reciprocal exchange of genetic material between chromosome 22 and chromosome 9, which leads to the production of the activated BCR-ABL1 gene and oncoprotein. The breakpoint in the BCR gene occurs commonly downstream of exons e13 or e14 (M-BCR) and less frequently downstream of exons e1 and e2 (m-BCR). Less than 1% of cases carry a breakpoint downstream of exon 6 or 8 ("variant fusion genes") or exon 19 (mu-BCR). Breakpoints in the ABL1 gene cluster upstream of exon a2 (or of exon a3 in less than 5% of patients with CIVIL). Conventional cytogenetic, fluorescence in situ hybridization, and molecular testing for the BCR-ABL1 fusion gene are key investigations for the diagnosis and monitoring of CIVIL. Treatment using tyrosine kinase inhibitors has revolutionized the management of CIVIL with hematologic and cytogenetic response within 12-18 months observed in > 85% of patients. Nevertheless, between 15 and 20% of patients may evolve to blastic phase. Measurement of low level or "minimal" residual disease using molecular tests is becoming the gold-standard approach to measure response to therapy due to its higher sensitivity compared to other routine techniques. The technical aspects and clinical applications of molecular monitoring will be the main focus of this article. Am. J. Hematol. 84:517-522, 2009. (C) 2009 Wiley-Liss, Inc.