p15(Ink4b) Loss of Expression by Promoter Hypermethylation Adds to Leukemogenesis and Confers a Poor Prognosis in Acute Promyelocytic Leukemia Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The p15(Ink4b) gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all French-American-British subtypes of acute myeloid leukemias, including acute promyelocytic leukemia (APL). In this study,we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir (North India). MATERIALS AND METHODS: p15 gene promoter hypermethylation was conducted by methylation-specific polymerase chain reaction, while its subsequent expression analysis was carried out by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of these 16 cases, seven (43.8%) were methylated partially and nine (56.2%) were found to have complete methylation. Moreover, nine of the 37 patients (24.3%) who presented with leukocytosis at their baseline had complete p15 gene methylation as well (p < 0.05). Semiquantitative RT-PCR showed a complete loss of p15 expression in nine patients with complete methylation coupled with leukocytosis (p=0.031), while seven patients with partial methylation showed decreased p15 expression. Six patients relapsed during the maintenance phase of treatment and were found to have a completely methylated p15 gene and no p15 mRNA. CONCLUSION: Complete methylation and loss of p15 gene expression causes susceptibility to relapse and decreased survival in APL patients. Thus, p15 promoter hypermethylation is a prospective prognostic indicator and a reliable clinical aid in assessment of patients with APL.

p15(Ink4b) Loss of Expression by Promoter Hypermethylation Adds to Leukemogenesis and Confers a Poor Prognosis in Acute Promyelocytic Leukemia Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The p15(Ink4b) gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all French-American-British subtypes of acute myeloid leukemias, including acute promyelocytic leukemia (APL). In this study,we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir (North India). MATERIALS AND METHODS: p15 gene promoter hypermethylation was conducted by methylation-specific polymerase chain reaction, while its subsequent expression analysis was carried out by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of these 16 cases, seven (43.8%) were methylated partially and nine (56.2%) were found to have complete methylation. Moreover, nine of the 37 patients (24.3%) who presented with leukocytosis at their baseline had complete p15 gene methylation as well (p < 0.05). Semiquantitative RT-PCR showed a complete loss of p15 expression in nine patients with complete methylation coupled with leukocytosis (p=0.031), while seven patients with partial methylation showed decreased p15 expression. Six patients relapsed during the maintenance phase of treatment and were found to have a completely methylated p15 gene and no p15 mRNA. CONCLUSION: Complete methylation and loss of p15 gene expression causes susceptibility to relapse and decreased survival in APL patients. Thus, p15 promoter hypermethylation is a prospective prognostic indicator and a reliable clinical aid in assessment of patients with APL.

Study of serum interleukin (IL) 18 and IL-6 levels in relation with the clinical disease severity in chronic idiopathic urticaria patients of Kashmir (North India)

BACKGROUND: Chronic urticaria is termed as idiopathic if there is an absence of any identifiable causes of mast cell and basophil degranulation. Various cytokines have been found to be involved in inflammatory processes associated with chronic idiopathic urticaria, including interleukin (IL) 18 and IL-6. OBJECTIVE: To evaluate any possible correlation of IL-18 and IL-6 cytokines with the clinical disease severity in chronic idiopathic urticaria (CIU). METHODS: IL-18 and IL-6 levels of CIU patients (n = 62) and healthy controls (n = 27) were assessed by commercially available enzyme linked immunosorbent assay kits following the manufacturer's protocols. RESULTS: Serum IL-18 concentration (mean ± standard deviation [SD], 62.95 ± 36.09 pg/mL) in CIU patients and in healthy controls (54.35 ± 18.45 pg/mL) showed no statistical significance (p > 0.05). No statistically significant difference (p > 0.05) was observed between autologous serum skin test (ASST) positive and ASST negative patients with regard to the serum IL-18 levels either. Similarly, serum IL-6 concentration (0.82 ± 4.6 pg/mL) in CIU patients and in healthy controls (0.12 ± 1.7 pg/mL), showed no statistical significance (p > 0.05). Also, comparison between positive and ASST negative patients with regard to the serum IL-6 levels was statistically nonsignificant (p > 0.05). However, statistical significance was found both in IL-18 and IL-6 concentrations in certain grades with regard to the clinical disease severity of urticaria. CONCLUSION: There is no significant association as such found between IL-18 and IL-6 levels with CIU, however, these cytokines may help in predicting the clinical disease severity in CIU. Hence, these cytokines may indicate a potential role as a biomarker to assess the disease severity in CIU.