Somatic Mutation in Immunoglobulin Gene Variable Region in Patients with Chronic Lymphoid Leukemia and its Influence on Patient's Prognosis in Iran

Chronic Lymphocytic Leukemia (CLL) is among the most prevalent blood cancers in people over the age of 40. In addition to clinical-pathologic staging and blood tests, another crucial prognostic factor of CLL is the immunoglobulin variable heavy chain mutation analysis. Finding the most prevalent mutation type and conducting a molecular analysis of it in the majority of the patients can contribute to identifying the disease pattern in a specific region or country. In the present study, we have used molecular detection methods in order to find the relationship between clinical pathologic findings and immunoglobulin heavy chain mutations in CLL patients in Iran. From 2009-2011, 26 patients with a suspected diagnosis of CLL were randomly selected from patients referred to Imam Khomeini Hospital. All patients underwent a clinical staging of the disease and had flow cytometric analysis performed on blood samples. The panels of cell surface markers used for the diagnosis of Chronic Lymphoid Leukemia include CD19, CD3, CD23, CD10 and CD5. The diagnosis confirmed a minimum of 20% positive expression of dual CD5 and CD19 markers. Genomic DNA was then extracted from the patients’ blood and IGVH mutation analysis was conducted with pGEM-T kit. Patients were in an age range of 42 to 80, with their mean age being 62 (SE=1.87) and 73% of them being male. Their mean WBC count, lymphocytes percentage, average hemoglobin level and platelet count were, respectively, 56000/microliter, 85%, 12 gr/dl and 150000/microliter. According to their molecular analysis, 38.9% of patients were unmutated and 61.1% showed mutation in the variable heavy chain locus. The most common mutation had occurred in the IGVH3 allele (66.66%). The mean overall survival rate of patients, mutated and unmutated, was, respectively, 39 (95%CI 32, 46) and 31 (95%CI 26, 36) months (P=0.407).Benet stage had statistically meaningful relation to patients survival (p=0.02) Similar to the findings of other studies, IGVH3 mutations were found to be prevalent by this study too. Although a correlation was found to exist between the patients’ survival and IGVH mutation, it was not statistically significant due to the limited number of the patients. We can conclude that clinical methods are still valuable in determining the prognosis of patients with CLL today.