Title

Genomic amplification of chromosome 7 in the Doxorubicin resistant K562 cell line

Authors

Sara M. Ibrahim¹, Sajjad Karim², Heba Abusamra², Peter N. Pushparaj², Jalaluddin A. Khan¹, Adel M. Abuzenadah^2,3, Mamdooh A Gari², Sherin Bakhashab^1,5, Farid Ahmed^2,4*, Mohammed H. Al-Qahtani²

Affiliation

¹Department of Biochemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80218, Jeddah, 21589, Kingdom of Saudi Arabia; ²Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia; ³King Fahad Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia; ⁴Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia; ⁵KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Farid Ahmed - E-mail: fahmed1@kau.edu.sa; Phone: +966 535887428

Email

Acute myeloid leukemia, multi drug resistance, chromosome 7 amplification

Article Type

Hypothesis

Date

Received December 4, 2018; Accepted December 8, 2018; Published December 29, 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 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. Specifically, the amplicon contained ABCB1 gene locus at 7q21.1, showing 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 chromosome 7 region harboring the ABCB1 gene.

Keywords

Acute myeloid leukemia, multi drug resistance, chromosome 7 amplification

Citation

Ibrahim et al. Bioinformation 14(9): 587-593 (2018)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.