Ibrahim Sara M, Karim Sajjad, Abusamra Heba, Pushparaj Peter N, Khan Jalaluddin A, Abuzenadah Adel M, Gari Mamdooh A, Bakhashab Sherin, Ahmed Farid, Al-Qahtani Mohammed H
Department of Biochemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80218, Jeddah, 21589, Kingdom of Saudi Arabi.
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia.
Bioinformation. 2018 Dec 29;14(9):587-593. doi: 10.6026/97320630014587. eCollection 2018.
Acquisition of multi-drug resistance (MDR) is a major hindrance towards the successful treatment of cancers. Over expression of a range of ATP-dependent efflux pumps, particularly ABCB1 is a widely reported mechanism of cancer cell MDR. Approximately 30% acute myeloid leukemia (AML) patients demonstrate ABCB1 over expression. Several mechanisms for up regulation of ABCB1 have been proposed. Our aim was to investigate the role of genomic amplification of the chromosome 7 region with regard to its influence on ABCB1 over expression in AML cell line. For this, we developed Doxorubicin (Dox) resistant leukemic cell line from K562 cells, demonstrating MDR phenotype. The chromosomal changes associated with the acquisition of MDR were characterized by array- based comparative genomic hybridization (aCGH) with the parental K562 cell line as the reference genome. Significant genomic gains in the chromosomal region corresponding to 7q11.21-7q22.1 were observed in Dox selected cell line. Moreover, the amplicon contains the ABCB1 gene locus at 7q21.1 with a copy number gain of >4. ABCB1 mRNA was found to be up-regulated by54-fold. Our results demonstrate that the development of MDR in K562/Dox is underlined by a genomic amplification of the chromosome 7 region harboring the ABCB1 gene.
获得多药耐药性（MDR）是癌症成功治疗的主要障碍。一系列ATP依赖性外排泵的过度表达，尤其是ABCB1，是癌细胞MDR的一种广泛报道的机制。大约30%的急性髓性白血病（AML）患者表现出ABCB1过度表达。已经提出了几种上调ABCB1的机制。我们的目的是研究7号染色体区域的基因组扩增在AML细胞系中对ABCB1过度表达的影响方面的作用。为此，我们从K562细胞中培养出对阿霉素（Dox）耐药的白血病细胞系，表现出MDR表型。以亲本K562细胞系作为参考基因组，通过基于阵列的比较基因组杂交（aCGH）对与获得MDR相关的染色体变化进行了表征。在Dox选择的细胞系中观察到对应于7q11.21-7q22.1的染色体区域有显著的基因组增益。此外，扩增子包含位于7q21.1的ABCB1基因座，拷贝数增益>4。发现ABCB1 mRNA上调了54倍。我们的结果表明，K562/Dox中MDR的发展是由含有ABCB1基因的7号染色体区域的基因组扩增所突出显示的。
