ACTIVATING POINT MUTATIONS IN THE BETA(C) CHAIN OF THE GM-CSF, IL-3 AND IL-5 RECEPTORS ARE NOT A MAJOR CONTRIBUTORY FACTOR IN THE PATHOGENESIS OF ACUTE MYELOID-LEUKEMIA

A number of mutant growth factor receptors have been described which a re constitutively activated and confer factor independence on growth f actor dependent cells, possibly through constitutive dimerization in t he absence of ligand or induction of a conformational change. Mutation s in receptor chains may therefore contribute to the pathogenesis of h aemopoietic malignancies, for example by causing constitutive receptor activation or uncontrolled downstream signalling. Since most of the a ctivated mutants reported for the beta(c) chain of the GM-CSF/IL-3/IL- 5 receptor involve point mutations or truncations of the extracellular domain, we have analysed the coding sequence of this region using RT- PCR-SSCP of RNA from blast cells of 31 patients with acute myeloid leu kaemia (AML). Two point mutations detected were silent, C-301 --> T (C ys91) and C-1306 --> T (Ser426). The latter had previously been identi fied with an allele frequency of 0.13 in the general population. Two f urther point mutations detected led to amino acid substitutions, G(773 ) --> C (Glu249Gln), which is equivalent to the mouse sequences, and G (962) --> A (Asp312Asn), both of which were found at similar frequenci es in normal controls. Activating mutations of the beta(c) chain which might contribute to the pathogenesis of the disease are therefore rar e in AML.