Dicer Gene Expression as a Prognostic Factor in Acute Lymphoblastic Leukemia and Chronic Lymphocytic Leukemia in Fars Province

Farzaneh, Mohamad Reza; Shahryari, Jahanbanoo; Safaei, Akbar; Valibeigi, Behnaz; Karimi Davani, Shahrbanou; Tabibi, Narjes

Dicer Gene Expression as a Prognostic Factor in Acute Lymphoblastic Leukemia and Chronic Lymphocytic Leukemia in Fars Province

Document Type : Brief Report(s)

Authors

Mohamad Reza Farzaneh ¹

Jahanbanoo Shahryari ²

Akbar Safaei ³

Behnaz Valibeigi ³

Shahrbanou Karimi Davani ⁴

Narjes Tabibi ³

¹ Department of Pathology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran

² Department of Pathology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

³ Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

⁴ Department of Biology, School of Sciences, University of Sistan and Baluchistan, Zahedan, Iran

Abstract

Alterations in the expression of microRNAs (miRNAs) have been proposed to play a role in the pathogenesis of acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL). Dicer is one of the main regulators of miRNA biogenesis, and deregulation of its expression has been indicated as a possible cause of miRNA alterations observed in various cancers. Our aim was to analyze the expression of the Dicer protein and its relationship with ALL and CLL. This cross-sectional study was performed from 2010 to 2012 in Shahid Faghihi Hospital, Shiraz, Iran. In this study, 30 patients with CLL, 21 patients with ALL, 10 child healthy donors, and 19 adult healthy donors were recruited. The patients’ samples were checked via flow cytometry, immunohistochemistry, and immunocytochemistry. The controls’ samples were also examined in the hematology ward. Total RNA was extracted from the bone marrow and peripheral blood samples of the patients and controls. Then, reverse-transcription polymerase chain reaction was used to estimate the level of Dicer miRNA. The outcomes of the expression analysis of Dicer revealed statistically significant differences between the ALL patients/child healthy controls (mean±SD, 0.19±0.28 vs. 0.73±0.12; P<0.001) and the CLL patients/adult healthy controls (mean±SD, 0.24±0.25 vs. 0.41±0.28; P=0.033). This is the first piece of evidence showing that the expression of the Dicer gene greatly decreased in the patients with ALL in comparison to the child controls. The expression of the Dicer gene was also downregulated in the patients with CLL compared to the adult controls. Given the above findings, the expression of Dicer may play an important role in the progression and prognosis of these diseases.

Keywords

DICER1 protein

Gene expression

Leukemia

- Cancer Treatment and Survivorship Facts & Figures 2014-2015 [Internet]. American Cancer Society. [cited 2014 Dec 8]. Available from: http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-042801.pdf
- Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet. 2008;371:1030-43. doi: 10.1016/S0140-6736(08)60457-2. PubMed PMID: 18358930.
- Cancer Facts & Figures 2014 [Internet]. American Cancer Society. [Cited 2014 Dec 8]. Available from: http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf.
- Mehrabani D, Tabei S, Heydari S, Shamsina S, Shokrpour N, Amini M, et al. Cancer occurrence in Fars Province, Southern Iran. Iran Red Crescent Med J. 2008;10:314-22.
- Belson M, Kingsley B, Holmes A. Risk factors for acute leukemia in children: a review. Environ Health Perspect. 2007;115:138-45. doi: 10.1289/ehp.9023. PubMed PMID: 17366834; PubMed Central PMCID: PMC1817663.
- Zhang S, Kipps TJ. The pathogenesis of chronic lymphocytic leukemia. Annu Rev Pathol. 2014;9:103-18. doi: 10.1146/annurev-pathol-020712-163955. PubMed PMID: 23987584; PubMed Central PMCID: PMC4144790.
- Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9-29. doi: 10.3322/caac.21208. PubMed PMID: 24399786.
- Mozaheb Z. Epidemiology of Lymphoid Malignancy in Asia. Croatia: INTECH Open Access Publisher; 2012.
- Xu L, Liang YN, Luo XQ, Liu XD, Guo HX. Association of miRNAs expression profiles with prognosis and relapse in childhood acute lymphoblastic leukemia. Zhonghua Xue Ye Xue Za Zhi. 2011;32:178-81. PubMed PMID: 21535956.
- Moussay E, Wang K, Cho JH, van Moer K, Pierson S, Paggetti J, et al. MicroRNA as biomarkers and regulators in B-cell chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2011;108:6573-8. doi: 10.1073/pnas.1019557108. PubMed PMID: 21460253; PubMed Central PMCID: PMC3081030.
- Zhu DX, Fan L, Lu RN, Fang C, Shen WY, Zou ZJ, et al. Downregulated Dicer expression predicts poor prognosis in chronic lymphocytic leukemia. Cancer Sci. 2012;103:875-81. doi: 10.1111/j.1349-7006.2012.02234.x. PubMed PMID: 22320315.
- Ji X. The mechanism of RNase III action: how dicer dices. Curr Top Microbiol Immunol. 2008;320:99-116. PubMed PMID: 18268841.
- Merritt WM, Lin YG, Han LY, Kamat AA, Spannuth WA, Schmandt R, et al. Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med. 2008;359:2641-50. doi: 10.1056/NEJMoa0803785. PubMed PMID: 19092150; PubMed Central PMCID: PMC2710981.
- Lin RJ, Lin YC, Chen J, Kuo HH, Chen YY, Diccianni MB, et al. microRNA signature and expression of Dicer and Drosha can predict prognosis and delineate risk groups in neuroblastoma. Cancer Res. 2010;70:7841-50. doi: 10.1158/0008-5472.CAN-10-0970. PubMed PMID: 20805302; PubMed Central PMCID: PMC4095771.
- Wu JF, Shen W, Liu NZ, Zeng GL, Yang M, Zuo GQ, et al. Down-regulation of Dicer in hepatocellular carcinoma. Med Oncol. 2011;28:804-9. doi: 10.1007/s12032-010-9520-5. PubMed PMID: 20405249.
- Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446-56. doi: 10.1182/blood-2007-06-093906. PubMed PMID: 18216293; PubMed Central PMCID: PMC2972576.
- Klein U, Lia M, Crespo M, Siegel R, Shen Q, Mo T, et al. The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell. 2010;17:28-40. doi: 10.1016/j.ccr.2009.11.019. PubMed PMID: 20060366.
- Costinean S, Sandhu SK, Pedersen IM, Tili E, Trotta R, Perrotti D, et al. Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic mice. Blood. 2009;114:1374-82. doi: 10.1182/blood-2009-05-220814. PubMed PMID: 19520806; PubMed Central PMCID: PMC2727407.
- Koralov SB, Muljo SA, Galler GR, Krek A, Chakraborty T, Kanellopoulou C, et al. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell. 2008;132:860-74. doi: 10.1016/j.cell.2008.02.020. PubMed PMID: 18329371.
- Xu S, Guo K, Zeng Q, Huo J, Lam KP. The RNase III enzyme Dicer is essential for germinal center B-cell formation. Blood. 2012;119:767-76. doi: 10.1182/blood-2011-05-355412. PubMed PMID: 22117047.
- Grelier G, Voirin N, Ay AS, Cox DG, Chabaud S, Treilleux I, et al. Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype. Br J Cancer. 2009;101:673-83. doi: 10.1038/sj.bjc.6605193. PubMed PMID: 19672267; PubMed Central PMCID: PMC2736830.
- Zighelboim I, Reinhart AJ, Gao F, Schmidt AP, Mutch DG, Thaker PH, et al. DICER1 expression and outcomes in endometrioid endometrial adenocarcinoma. Cancer. 2011;117:1446-53. doi: 10.1002/cncr.25665. PubMed PMID: 21425145; PubMed Central PMCID: PMC3065965.
- He L, Wang HY, Zhang L, Huang L, Li JD, Xiong Y, et al. Prognostic significance of low DICER expression regulated by miR-130a in cervical cancer. Cell Death Dis. 2014;5:e1205. doi: 10.1038/cddis.2014.127. PubMed PMID: 24787017; PubMed Central PMCID: PMC4047899.
- Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 2007;39:673-7. doi: 10.1038/ng2003. PubMed PMID: 17401365.
- Chiosea S, Jelezcova E, Chandran U, Luo J, Mantha G, Sobol RW, et al. Overexpression of Dicer in precursor lesions of lung adenocarcinoma. Cancer Res. 2007;67:2345-50. doi: 10.1158/0008-5472.CAN-06-3533. PubMed PMID: 17332367.
- Fujino T, Risinger JI, Collins NK, Liu FS, Nishii H, Takahashi H, et al. Allelotype of endometrial carcinoma. Cancer Res. 1994;54:4294-8. PubMed PMID: 8044774.
- Sercan HO, Sercan ZY, Kizildag S, Undar B, Soydan S, Sakizli M. Consistent loss of heterozygosity at 14Q32 in lymphoid blast crisis of chronic myeloid leukemia. Leuk Lymphoma. 2000;39:385-90. doi: 10.3109/10428190009065838. PubMed PMID: 11342319.
- Agueli C, Cammarata G, Salemi D, Dagnino L, Nicoletti R, La Rosa M, et al. 14q32/miRNA clusters loss of heterozygosity in acute lymphoblastic leukemia is associated with up-regulation of BCL11a. Am J Hematol. 2010;85:575-8. doi: 10.1002/ajh.21758. PubMed PMID: 20578197.
- Rio Frio T, Bahubeshi A, Kanellopoulou C, Hamel N, Niedziela M, Sabbaghian N, et al. DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. JAMA. 2011;305:68-77. doi: 10.1001/jama.2010.1910. PubMed PMID: 21205968; PubMed Central PMCID: PMC3406486.
- Pampalakis G, Diamandis EP, Katsaros D, Sotiropoulou G. Down-regulation of dicer expression in ovarian cancer tissues. Clin Biochem. 2010;43:324-7. doi: 10.1016/j.clinbiochem.2009.09.014. PubMed PMID: 19782670.