Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Int J Lab Hematol. 2021 Aug;43(4):713-723. doi: 10.1111/ijlh.13451. Epub 2021 Jan 2.
Accurate detection of GATA1 mutation is highly significant in patients with acute myeloid leukemia (AML) and trisomy 21 as it allows optimization of clinical protocol. This study was aimed at (a) enhanced search for GATA1 mutations; and (b) characterization of molecular landscapes for such conditions.
The DNA samples from 44 patients with newly diagnosed de novo AML with trisomy 21 were examined by fragment analysis and Sanger sequencing of the GATA1 exon 2, complemented by targeted high-throughput sequencing (HTS).
Acquired GATA1 mutations were identified in 43 cases (98%). Additional mutations in the genes of JAK/STAT signaling, cohesin complex, and RAS pathway activation were revealed by HTS in 48%, 36%, and 16% of the cases, respectively.
The GATA1 mutations were reliably determined by fragment analysis and/or Sanger sequencing in a single PCR amplicon manner. For patients with extremely low blast counts and/or rare variants, the rapid screening with simple molecular approaches must be complemented with HTS. The JAK/STAT and RAS pathway-activating mutations may represent an extra option of targeted therapy with kinase inhibitors.
在患有急性髓系白血病（AML）和 21 三体的患者中，准确检测 GATA1 突变具有重要意义，因为它可以优化临床方案。本研究旨在：（a）增强对 GATA1 突变的搜索；（b）描述此类情况下的分子图谱。
对 44 例新诊断的伴有 21 三体的初发 AML 患者的 DNA 样本进行了片段分析，并对 GATA1 外显子 2 进行了 Sanger 测序，同时辅以靶向高通量测序（HTS）。
在 43 例（98%）中发现了获得性 GATA1 突变。通过 HTS 在 48%、36%和 16%的病例中分别揭示了 JAK/STAT 信号转导、黏合复合物和 RAS 通路激活基因的额外突变。
通过片段分析和/或 Sanger 测序以单个 PCR 扩增子的方式可靠地确定了 GATA1 突变。对于极低的原始细胞计数和/或罕见变异的患者，必须用简单的分子方法进行快速筛选，然后再进行 HTS。JAK/STAT 和 RAS 通路激活突变可能代表着用激酶抑制剂进行靶向治疗的额外选择。
