Adamaki Maria, Vlahopoulos Spiros, Lambrou George I, Papavassiliou Athanasios G, Moschovi Maria
1 Pediatric Hematology/Oncology Unit, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens and "Aghia Sofia" Children's Hospital, Athens, Greece.
2 Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Tumour Biol. 2017 Mar;39(3):1010428317694308. doi: 10.1177/1010428317694308.
The AML1 ( acute myeloid leukemia 1) gene, a necessary prerequisite of embryonic hematopoiesis and a critical regulator of normal hematopoietic development, is one of the most frequently mutated genes in human leukemia, involving over 50 chromosome translocations and over 20 partner genes. In the few existing studies investigating AML1 gene expression in childhood leukemias, aberrant upregulation seems to specifically associate with AML1 translocations and amplifications. The aim of this study was to determine whether overexpression also extends to other leukemic subtypes than the ones karyotypically involving AML1. We use quantitative real-time polymerase chain reaction methodology to investigate gene expression in 100 children with acute leukemias and compare them to those of healthy controls. We show that in childhood acute lymphoblastic leukemia, AML1 gene overexpression is associated with a variety of leukemic subtypes, both immunophenotypically and cytogenetically. Statistically significantly higher transcripts of the gene were detected in the acute lymphoblastic leukemia group as compared to the acute myeloid leukemia group, where AML1 overexpression appeared to associate with cytogenetic abnormalities additional to those that engage the AML1 gene, or that are reported as showing a "normal" karyotype. Collectively, our study shows that AML1 gene overexpression characterizes a broader range of leukemic subtypes than previously thought, including various maturation stages of B-cell acute lymphoblastic leukemia and cytogenetic types additional to those involving the AML1 gene.
AML1（急性髓系白血病1）基因是胚胎造血的必要前提条件，也是正常造血发育的关键调节因子，是人类白血病中最常发生突变的基因之一，涉及50多种染色体易位和20多种伙伴基因。在现有的少数关于儿童白血病中AML1基因表达的研究中，异常上调似乎与AML1易位和扩增特别相关。本研究的目的是确定AML1基因的过表达是否也扩展到除了核型涉及AML1的白血病亚型之外的其他白血病亚型。我们使用定量实时聚合酶链反应方法来研究100例急性白血病儿童的基因表达，并将其与健康对照者的基因表达进行比较。我们发现，在儿童急性淋巴细胞白血病中，AML1基因过表达与多种白血病亚型相关，包括免疫表型和细胞遗传学方面。与急性髓系白血病组相比，急性淋巴细胞白血病组中该基因的转录本在统计学上显著更高，在急性髓系白血病组中，AML1过表达似乎与除涉及AML1基因的那些异常之外的细胞遗传学异常相关，或者与报告为显示 “正常” 核型的异常相关。总的来说，我们的研究表明，AML1基因过表达所表征的白血病亚型范围比以前认为的更广，包括B细胞急性淋巴细胞白血病的各种成熟阶段以及除涉及AML1基因的那些细胞遗传学类型之外的其他类型。
