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        Investigating the expression pattern of the angiopoietin-Tie system in ALL and its correlation with baseline characteristics

        Saeed Zaka Khosravi,Samira Molaei Ramshe,Mehdi Allahbakhshian Farsani,Saeed Solali,Mohammadreza Moonesi,Majid Farshdousti Hagh 대한혈액학회 2021 Blood Research Vol.56 No.2

        Background Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children. Several environmental and genetic factors are known to be involved in its development and progression. The angiopoietin-Tie system is one of the most critical factors in angiogenesis, and its possible role in solid tumors and leukemia has been previously investigated. In this study, we examined the expression of these genes in ALL patients (early pre-B-ALL and pre-B-ALL) and compared them with normal samples. Methods Bone marrow samples were collected from 40 patients (aged 0‒19 yr) newly diagnosed with early pre-B-ALL or pre-B-ALL using molecular and flow cytometric tests and from 15 control individuals. For molecular tests, RNA extraction and cDNA synthesis were performed, and Ang1, Ang2, Ang4, Tie1, and Tie2 gene expression was examined by real-time polymerase chain reaction. Results Ang2, Tie1, and Tie2 gene expression were significantly increased in patients with ALL, whereas Ang1 gene expression was decreased. The Ang4 gene did not show significant expression changes between the two groups. Conclusion Changes in the expression of the Ang-Tie system indicate a possible role of angiogenesis in ALL prognosis. Moreover, such changes can be considered as potential diagnostic biomarkers or therapeutic targets.

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        An investigation of methylation pattern changes in the IKZF1 promoter in patients with childhood B-cell acute lymphoblastic leukemia

        Mina Rahmani,Masoumeh Fardi,Majid Farshdousti Hagh,Abbas Ali Hosseinpour Feizi,Mehdi Talebi,Saeed Solali 대한혈액학회 2019 Blood Research Vol.54 No.2

        BackgroundIkaros family zinc finger 1 (IKZF1)is a transcription factor with an important role in control-ling 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 (hypomethylat-ion) of the IKZF1 promoter region might be one of the causes of B-cell acute lymphoblastic leukemia (B-ALL). In B-ALL patients, an increased expression of this gene is a potential cause of B-cell differentiation arrest and proliferation induction. Therefore, as more than 90% of patients with ALL are <15 years old, we investigated the methylation pattern of the IKZF1 promoter in childhood B-ALL.MethodsTwenty-five newly diagnosed B-ALL cases were included (all younger than 15 yr). In addi-tion, we selected 25 healthy age- and sex-matched children as the control group. We col-lected 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 phe-nol/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.ResultsOur 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 parti-ally methylated (68%).ConclusionThis study demonstrated a hypomethylated pattern of the IKZF1 promoter region in child-hood B-ALL, which might underlie the aberrant Ikaros expression patterns that were pre-viously linked to this malignancy.

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