Transcriptomic Profiles of MV4-11 and Kasumi 1 Acute Myeloid Leukemia Cell Lines Modulated by Epigenetic Modifiers Trichostatin A and 5-Azacytidine

Keywords:
Acute myeloid leukemia, Epigenetics, Histone deacetylase inhibitor, 5-Azacytidine, Gene expression

Abstract

Background:Acute myeloid leukemia (AML) is the most common form of acute leukemias in adults which is clinically and molecularly heterogeneous. Several risk and genetic factors have been widely investigated to characterize AML. However, the concomitant epigenetic factors in controlling the gene expression lead to AML transformation was not fully understood. This study was aimed to identify epigenetically regulated genes in AML cell lines induced by epigenetic modulating agents, Trichostatin A (TSA) and 5-Azacytidine (5-Aza).

Methods:MV4-11 and Kasumi 1 were treated with TSA and/or 5-Aza at IC50concentration. Gene expression profiling by microarray was utilized using SurePrint G3 Human Gene Expression v3. Gene ontology and KEGG pathway annotations were analyzed by DAVID bioinformatics software using EASE enrichment score. mRNA expression of the differentially expressed genes were verified by quantitative real time PCR.

Results:Gene expression analysis revealed a significantchanges in the expression of 24,822, 15,720, 15,654 genes in MV4-11 and 12,598, 8828, 18,026 genes in Kasumi 1, in response to TSA, 5-Aza and combination treatments, respectively, compared to non-treated (p<0.05). 7 genes (SOCS3,TUBA1C, CCNA1, MAP3K6, PTPRC, STAT6and RUNX1) and 4 genes (ANGPTL4, TUBB2A, ADAM12and PTPN6) shown to be predominantly expressed in MV4-11 and Kasumi 1, respectively (EASE<0.1). The analysis also revealed phagosome pathway commonly activated in both cell lines.

Conclusion:Our data showed a distinct optimal biological characteristic and pathway in different types of leukemic cell lines. These finding may help in the identification of cell-specific epigenetic biomarker in the pathogenesis of AML.

Author Biographies

Mat Jusoh Siti Asmaa, Universiti Sains Malaysia

Department of Hematology,

School of Medical Sciences,

Universiti Sains Malaysia,

16150 Kubang Kerian,

Kelantan,

Malaysia.

Hamid Ali Al-Jamal, Universiti Sultan Zainal Abidin

Diagnostic and Biomedicine,

Faculty of Health Sciences,

Universiti Sultan Zainal Abidin,

Gong Badak Campus,

Kuala Nerus,

21300, Terengganu,

Malaysia.

Abdul Rahim Hussein, Universiti Sains Malaysia

Regenerative Medicine Cluster,

Advanced Medical And Dental Institute,

Universiti Sains Malaysia,

Bertam, 13200 Kepala Batas,

Pulau Pinang,

Malaysia.

Badrul Hisham Yahaya, Universiti Sains Malaysia

Regenerative Medicine Cluster,

Advanced Medical And Dental Institute,

Universiti Sains Malaysia,

Bertam, 13200 Kepala Batas,

Pulau Pinang,

Malaysia.

Azlan Husin, Universiti Sains Malaysia

Department of Internal Medicine,

School of Medical Sciences,

Universiti Sains Malaysia,

16150 Kubang Kerian,

Kelantan,

Malaysia.

Rosline Hassan, Universiti Sains Malaysia

Department of Hematology,

School of Medical Sciences,

Universiti Sains Malaysia,

16150 Kubang Kerian,

Kelantan,

Malaysia.

Faezahtul Arbaeyah Hussain, Universiti Sains Malaysia

Department of Pathology,

School of Medical Sciences,

Universiti Sains Malaysia,

16150 Kubang Kerian,

Kelantan,

Malaysia.

Shaharum Shamsuddin, Universiti Sains Malaysia

1School of Health Sciences,

2Institute for Research in Molecular Medicine (INFORMM),

Universiti Sains Malaysia,

16150 Kubang Kerian,

Kelantan,

Malaysia.

Muhammad Farid Johan, Universiti Sains Malaysia

Department of Hematology,

School of Medical Sciences,

Universiti Sains Malaysia,

16150 Kubang Kerian,

Kelantan,

Malaysia.

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Published
2020-01-01
How to Cite
1.
Siti Asmaa MJ, Al-Jamal HA, Hussein AR, Yahaya BH, Husin A, Hassan R, Hussain FA, Shamsuddin S, Johan MF. Transcriptomic Profiles of MV4-11 and Kasumi 1 Acute Myeloid Leukemia Cell Lines Modulated by Epigenetic Modifiers Trichostatin A and 5-Azacytidine. Int J Hematol Oncol Stem Cell Res. 14(1):72-92.
Section
Original Article(s)