Blood Res  
An investigation of methylation pattern changes in the IKZF1 promoter in patients with childhood B-cell acute lymphoblastic leukemia
Mina Rahmani1,2, Masoumeh Fardi1,6, Majid Farshdousti hagh1,4, Mehdi Talebi3, Abbas Ali Hosseinpour Feizi3, Saeed Solali1,5
1Stem cell Research Center, 2Hematology and Oncology Research Center, 3Drug Applied Research Center, 4Molecular Medicine Research Center, 5Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Correspondence to: Solali Saeed, Ph.D.
Department of Immunology, Division of Hematology and Transfusion Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, East Azerbaijan Province, Tabriz, University Main St, Iran
Published online: May 24, 2019.
© The Korean Journal of Hematology. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: Ikaros family zinc finger 1 (IKZF1) is a transcription factor with an important role in controlling hematopoietic proliferation and function, particularly lymphoid cell differentiation. It was previously shown that various mechanisms and expression patterns of Ikaros are linked to a variety of cancers. We hypothesized that aberrant methylation (hypomethylation) of the IKZF1 promoter region causes excessive IKZF1 expression. In B-cell acute lymphoblastic leukemia (B-ALL) patients, an increased expression of this gene is a potential cause of B-cell differentiation arrest and proliferation induction. Therefore, we investigated the methylation pattern of the IKZF1 promoter in childhood B-ALL in the present study.

Methods: Twenty-five newly diagnosed B-ALL cases were included (all younger than 15 yr). In addition, we selected 25 healthy age- and sex-matched children as the control group. We collected the blood samples in EDTA-containing tubes and isolated lymphocytes from whole blood using Ficoll 1.077 Lymphosep. Next, we extracted genomic DNA with the phenol/chloroform method. Two microgram of DNA per sample was treated with sodium bisulfite using the EpiTect Bisulfite Kit, followed by an assessment of DNA methylation by polymerase chain reaction (PCR) analysis of the bisulfite-modified genomic DNA.

Results: Our data highlighted a hypomethylated status of the IKZF1 promoter in the ALL cases (96% of the cases were unmethylated). In contrast, the control group samples were partially methylated (68%).

Conclusion: This study demonstrated a hypomethylated pattern of the IKZF1 promoter region in childhood B-ALL, which might underlie the aberrant Ikaros expression patterns that were previously linked to this malignancy.

Keywords: Leukemia, Ikaros, IKZF1, DNA methylation, Hematological malignancy


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