Detection of a point mutation at codon 12 of the Kirsten-Ras [K-ras] oncogen in myelodysplastic syndrome

Mutations in ras genes have been observed in a variety of cancers and were found to play an important role in human leukemogenesis and in preleukemic disease as myelodysplastic syndrome [MDS]. The purpose of this study was to determine the prevalence of mutated K-ras oncogene in myelodysplastic syndrome [MDS]; with a special emphasis on their possible role in affecting clinical status, relation to karyotypic pattern; response to therapeutic measures; its impact on the fate of the disease and overall survival. Detection of point mutation of Kirsten-ras [K-ras] gene in 30 patients suffering from myelodysplastic syndrome was carried out using quantitative enriched polymerase chain reaction [QEPCR] and was confirmed by sequencing. QEPCR is a two- stage PCR procedure with modified primers that enriches mutant alleles, via restriction endonuclease digestion of normal alleles and enables identification of one mutant allele among 100,000 normal alleles. Activating mutations of the codon 12 of K-ras gene were detected in 7/30 [23.3%] cases of MDS, the most common mutation involved a substitution of aspartic acid for glycine [GGTGAT]. The incidence of K-ras mutations was found to be significantly associated with refractory anemia with excess blasts type II [RAEBII] and unclassified [UC] MDS than other subtypes [p=0.005], and was significantly associated with hypercellular bone marrow [p=0.04] showing marked dyserythropoitic changes. Furthermore, mutant K-ras gene was found to be significantly associated with abnormal karyotypes [p=0.04]. Patients with mutated K-ras gene were significantly associated with either high or intermediate risk according to International Prognostic Scoring System [IPSS] [p=0.001]. 6/7[85.7%] of those carrying the mutation showed poor response to treatment compared to non carriers with a statistical significant difference [p=0.009]. Five out of eight [62.5%] patients who were transformed to AML carried the mutant K-ras gene, their subtypes were RAEBII and unclassified MDS with abnormal cytogenetics mainly Monosomy 7. Overall survival was detected using Kaplan-Meier curve and the mean survival time of patients who carried K-ras mutations were significantly lower than those without the mutation [Log rank test=12.7; p=0.0004]. MDS patients bearing an mutated K-ras oncogene frequently showed poor response to treatment; leukemic progression of the disease and shorter overall survival, suggesting that an activated K-ras oncogene is a critical factor for prognostic evaluation; therapeutic decision and monitoring of response to treatment of MDS patients

Validity of platelet count/spleen diameter ratio as a predictor of esophageal varices in patients with liver cirrhosis

Portal hypertension commonly accompanies the presence of liver cirrhosis, and the development of esophageal varices [OV] is one of the major complications of portal hypertension. To evaluate platelet count/splenic size ratio as a non-invasive parameter to predict the presence or absence of esophageal varices in patients with liver cirrhosis. Eighty-six cirrhotic patients who underwent digestive upper endoscopy, were classified into Group 1 which is formed of 60 patients who had endoscopic evidence of OV and Group 2 which is formed of 26 patients who had no endoscopic evidence of OV. All the patients underwent thorough clinical examination, laboratory and ultrasonographic evaluation. Laboratory investigations were done in the form of complete blood count including platelet count [PLT]; liver function tests [aspartate transaminase [AST], alanine aminotransferase [ALT], serum bilirubin and prothrombin time [PT]], schistosomal antibodies, hepatitis B surface antigen [HBsAg] and hepatitis C virus antibodies. Abdominal ultrasonography and upper gastrointestinal endoscopy were done for all patients. Patients with OV had lower mean platelet count and higher mean spleen diameter than patients without OV [p=0.003 and p=0.01 respectively]. The mean values of the ratio of platelet count/spleen diameter was significantly lower among OV group when compared with patients who had no endoscopic evidence of OV [p=0.002]. There was no significant difference in the platelet count/spleen diameter ratio between different grades of OV. Large OV was associated with increased portal vein diameter [p=0.05]. Lower platelet count/splenic size ratio is associated with the presence of OV yet it cannot be used as a predictor of OV and so the endoscopy remains the standard screening test for OV among patients with liver cirrhosis