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CancerGenetics

• Lack of Correlation Between the CCR5-D32 Mutation and Acute Myeloid Leukemia in Iranian Patients

• Zahra Zahiri,¹ Hossein Khorramdelazad,² Yousef Mortazavi,^3,* Mohammad Momeni,⁴ Mohammad Kazemi Arababadi,⁵ Behjat Kalantary Khandany,⁶
  1. Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  2. Department of Immunology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  3. Department of Molecular Medicine, Faculty of Medicine, Zanjan University of Medical Sciences, 4513956111 Zanjan, Iran
  4. Department of Immunology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  5. Department of Immunology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  6. Department of Hematology-Oncology and BMT, Kerman University of Medical Sciences, Kerman, Iran
  
  
  
• Introduction: Iran is reported as a region with low prevalance for AML [1, 2]. Several studies proposed that differences in host genetic and epigenetic settings between AML patients and healthy controls could be responsible for the development of this cancer occurrence [3]. Chemokines are a subgroup of cytokines with several biological effects such as recruitment of leukocytes to the sites of injury/infection, angiogenesis, and angiostatic properties [4, 5]. The CC the CCR5 is a specific chemokine receptor for CC chemokine ligands CCL3, CCL4 and CCL5, all play key part in localization of infiltrated leukemia cells [6]. Therefore, it is plausible to hypothesize that down-regulation of this receptor may lead to low proliferation and infiltration leucocyte progenitor cells in AML. It is now well established that deletion of 32 nucleotides from the exon 1 of CCR5 (known as D32 mutation) causes decreased expression and in turn dysfunction of CCR5 receptor [7–9]. More recent evidences revealed that this polymorphic variant is different in populations with various ethnic groups [10, 11]. Thus, based on the possible mechanisms that have been postulated in which down-regulation of CCR5 may results in prevention of leukemic cells proliferation and metastasis. Therefore, the aim of the present study was to determine the CCR5-D32 mutation in the Iranian patients suffering from with AML compared to healthy individuals.
• Methods: Subjects Peripheral blood specimens were collected from 60 AML patients 300 healthy controls from 2008 to 2012, in Rafsanjan city (sought eastern part of Iran), in 5.5 mL EDTA pre-coated tubes. Patients were recruited for the study based on the assessment of their previous clinical history. AML patients and controls were matched for age, sex and socio-economical status. Socio-economic conditions of participants were assessed based on the levels of education and monthly income. The anti-coagulant treated specimens were subjected to genomic DNA extraction immediately after arrival at the laboratory. This study was approved by the ethical committee of the Rafsanjan University of Medical Sciences and written informed consent was obtained from all of participants, either patient or control subject, prior to sample collection. Genomic DNA Extraction and Polymorphism Analysis The whole genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) using a commercial kit purchased from Bioneer Company, South-Korea, and then the resultant DNA was stored at -20 C for further use. The CCR5-D32 mutation was determined using Gap-PCR technique with the primers which were designed in a manner that could cover complete deleted region. 188 bp fragment showed a wild type gene without CCR5-D32 mutation, while, the presence of a PCR product with 156 bp confirms CCR5- D32 mutation in the CCR5 gene. Furthermore PCR condition, the sequences of forward and reverse primers and gel electrophoresis were described in our previous studies [11–13]. Data Analysis and Statistical Methods Results were analyzed by T test statistical method and a P value less than 0.05 was considered as significant.
• Results: Results of this study showed that the CCR5-D32 mutation was not found in AML patients, while only three cases (3 %) of healthy controls exhibited heterozygotic from of this mutation. These results also did not show any significant difference between both groups (P[ 0.1).
• Conclusion: In summary, our study—representing the first evaluation of the CCR5- Δ 32 CCR5-Δ32 mutation in AML—revealed no correlation between this polymorphism and susceptibility to AML in Iranian patients. Although the CCR5/ligands axis plays a pivotal role in leukocyte proliferation and AML biology, CCR5 dysfunction in this population may be mediated by alternative genetic variants or epigenetic mechanisms. Further investigations across larger cohorts and varied ethnic backgrounds are required to validate these observations.
• Keywords: CCR5-D32 mutation Acute myeloblastic leukemia Chemokine