Mutations of the K-ras gene in childhood myelodysplastic syndrome

Abstract

The primary myelodysplastic syndrome (MDS) is a heterogeneous group of disorders characterized by a failure of the hematopoietic progenitors to differentiate normally, resulting in ineffective and dysplastic hematopoiesis of one or more cell lines. MDS is considered to be preleukemic state and in this context, it provides an opportunity to study molecular mechanisms that precede the development of leukemia. Molecular lesions underlying the evolution of MDS are largely unknown. Mutations of RAS genes have been found in variety of human hematologic malignancies including 5% to 30% of patients with MDS. The ras family of genes encodes 21-Kd guanosine triphosphate (GTP) - binding proteins that play an important role in growth and differentiation signal transduction. Usually, the mutations occur in codon 12, 13 and 61 of the exon I. These three positions are related to the domain of GTP-ase activity and if one of these suffer from mutation, activity of GTP-ase will be affected. The frequency of K-RAS point mutation was studied in 20 pediatric patients with MDs. Archival bone-marrow samples were screened by DNA amplification followed by single-strand conformation polymorphism (SSCP) at codon 12/13 and 61 of K-RAS exon I. No mutations of K-RAS gene were observed in our study suggesting that frequency of K-RAS mutation in childhood primary MDS may be lower than that for adults and that its role in leukemogenesis in primary and secondary MDS is different.