ras gene mutations and clonal analysis using RFLPs of X-chromosome genes in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal disorders characterized by quantitative and qualitative abnormalities of hematopoiesis [1, 2]. Up to 30% of cases eventually develop into acute nonlymphocytic leukemia (ANLL). Previous observations by us and others have demonstrated a frequent (30%) activation of the N-ras oncogene in ANLL [3-6]. The involvement of the different cell lineages in MDS has been rather controversial. Various approaches such as isoenzyme studies (G-6-PD polymorphisms), cytogenetic analysis (clonal chromosome abnormalities), and autosomal DNA polymorphism as markers of clonality have been employed to study the stem cell origin of MDS. However, these analyses produced conflicting data and have not clearly identified the stem cell origin of MDS [7 -12]. Although no accepted effective treatment exists for MDS, some studies have reported response rates of up to 30% to the administration of low-dose cytarabine (LD-AraC). However, the mechanism of LD-AraC treatment is not clear. Some data suggest that LD-AraC induces differentiation