Angelova S, Spassov B, Nikolova V, Christov I, Tzvetkov N, Simeonova M
Tsitol Genet. 2015 May-Jun;49(3):25-32.
The aim of our study was 1) to define if the amplification of c-MYC, MLL and RUNX1 genes is related to the progressive changes of the karyotype in patients with AML and MDS with trisomy 8, 11 and 21 (+8, +11 and +21) in bone marrow and 2) can that amplification be accepted as part of the clonal evolution (CE). Karyotype analysis was performed in 179 patients with AML or MDS with the different chromosomal aberrations (CA) aged 16-81. The findings were distributed as follow: initiating balanced CA (n = 60), aneuploidia (n = 55), unbalanced CA (n = 64). Amplification of c-MYC, MLL and RUNX1 genes by means of fluorescence in situ hybridization (FISH) was found in 35% (7 out of 20) of AML and MDS patients with +8, +11 u +21 as single CA in their karyotype; in 63.6% of pts (7 out of 11)--with additional numerical or structural CA and in 75% (9 out of 12)--with complex karyotype. We assume that the amplification of the respective chromosomal regions in patients with +8, +11 and +21 is related to CE. Considering the amplification as a factor of CE, we established 3 patterns of karyotype development depending on the type of the initiating CA in it. Significant statistical differences were found between the three patterns regarding the karyotype distribution in the different stages of progression (p < 0.001).
1）确定c-MYC、MLL和RUNX1基因的扩增是否与骨髓中存在8号、11号和21号三体（+8、+11和+21）的急性髓系白血病（AML）和骨髓增生异常综合征（MDS）患者核型的渐进性变化相关；2）该扩增能否被视为克隆进化（CE）的一部分。对179例年龄在16 - 81岁、患有不同染色体畸变（CA）的AML或MDS患者进行了核型分析。研究结果分布如下：起始平衡CA（n = 60）、非整倍体（n = 55）、不平衡CA（n = 64）。通过荧光原位杂交（FISH）发现，核型中单一CA为+8、+11和+21的AML和MDS患者中，35%（20例中的7例）存在c-MYC、MLL和RUNX1基因扩增；在有额外数量或结构CA的患者中，63.6%（11例中的7例）存在扩增；在有复杂核型的患者中，75%（12例中的9例）存在扩增。我们假设，+8、+11和+21患者中相应染色体区域的扩增与克隆进化有关。将扩增视为克隆进化的一个因素，我们根据起始CA的类型建立了3种核型发展模式。在不同进展阶段的核型分布方面，三种模式之间存在显著的统计学差异（p < 0.001）。
