Change of COMT Val158Met Genotype in Tumoral B Cells of a Chronic Lymphocytic Leukemia Patient: A Case Report

Case Report

Ann Hematol Oncol. 2017; 4(1): 1130.

Change of COMT Val158Met Genotype in Tumoral B Cells of a Chronic Lymphocytic Leukemia Patient: A Case Report

Sak K¹*, Kasemaa K¹ and Everaus H²

¹Department of Hematology and Oncology, University of Tartu, Estonia

²Clinic of Hematology and Oncology, Tartu University Hospital, Estonia

*Corresponding author: Katrin Sak, Department of Hematology and Oncology, Institute of Clinical Medicine, University of Tartu, L. Puusepa 8, 51014 Tartu, Estonia

Received: December 06, 2016; Accepted: January 30, 2017; Published: February 01, 2017


In this case report, a Chronic lymphocytic leukemia (CLL) female patient with a heterozygous polymorphism in the catechol-O-methyltransferase (COMT) gene is described. This functional change in the COMT enzyme Val158Met leads to a decreased efficacy to O-methylate different endogenous and exogenous compounds containing catechol structure, including hydroxylated estradiol intermediates, catecholamines and certain dietary flavonoids. The specific change found in tumoral B-cells as compared to the genomic DNA from the non-B fraction of peripheral blood mononuclear cells of the patient, could indicate that Val158Met might play some role in the pathogenesis of CLL that certainly needs further investigations. The possible application of this polymorphism as a potential biomarker of CLL is also worth of further largescale case-control studies.

Keywords: Biomarker; Catechol-O-methyltransferase; Chronic lymphocytic leukemia; O-methylation

Case Presentation

The venous blood sample was taken from a 64-year-old woman within a regular check-up. The patient had a 7-year history of chronic lymphocytic leukemia (B-CLL; Rai stage 1 and Binet stage A disease) and her hematological status was stable. As patient did not have any B symptoms, anemia or thrombocytopenia and she did not need any specific treatment according to the current CLL management approaches. Laboratorial findings revealed the white blood cell count (WBC) of 30x109/L with lymphocyte count of 25x109/L. Phenotype of the lymphocytes was determined as CD45+, CD19+, CD20+, CD5+, CD23+, CD43+, CD38-, FMC7-, CD79b-. Lymph nodes were observed only in cervical region with the diameter less than 1 cm. Fluorescence in situ hybridization revealed the presence of a monoallelic 13q deletion. The IGHV status of the patient as well as the expression of ZAP70 was not studied.

Peripheral blood mononuclear cells (PBMCs) were further separated from the whole blood sample using a density gradient technique (Ficoll-PaqueTM Premium, GE Healthcare). B cells were isolated from PBMCs by the human B-CLL Cell Isolation Kit from MACS Miltenyi Biotec. DNA was separated from whole blood sample, B cells and non-B fraction of PBMCs using QIAamp DNA Mini Kit (Qiagen) and the respective concentrations were determined by NanoDrop 2000C spectrophotometer (Thermo Scientific). Because of the recent increasing interest in possible role of phase II enzymes and their genetic variants in carcinogenesis [1], the fourth exon of catechol-O-methyltransferase (COMT) gene was amplified by polymerase chain reaction (PCR) and the COMT Val158Met (rs4680, G>A) genotype was determined by restriction analysis using FastDigest NIaIII (Hin1II, Thermo Scientific) as the restriction enzyme. Standard gel picture of three different genotypes (Val/Val, GG; Met/Met, AA and Val/Met, GA) is presented in the Figure 1A. The genotyping results of the patient demonstrated GG for the normal healthy non-B PBMCs but the genotype of tumoral B cells was changed to heterozygous GA (Figure 1B).

Citation:Sak K, Kasemaa K and Everaus H. Change of COMT Val158Met Genotype in Tumoral B Cells of a Chronic Lymphocytic Leukemia Patient: A Case Report. Ann Hematol Oncol. 2017; 4(1): 1130. ISSN : 2375-7965