THE BETA-SUBUNIT COMMON TO THE GM-CSF, IL-3 AND IL-5 RECEPTORS IS HIGHLY POLYMORPHIC BUT PATHOGENIC POINT MUTATIONS IN PATIENTS WITH ACUTE MYELOID-LEUKEMIA (AML) ARE RARE

The intracytoplasmic tail of the granulocyte-macrophage colony-stimula ting factor receptor (GM-CSFR) beta(c) chain is essential for the acti vation of ligand-mediated signal transduction pathways in myeloid cell s. Alterations in this region could deregulate normal signalling proce sses. We have therefore used RT-PCR-SSCP analysis of the receptor tail to look for point mutations in RNA from 35 patients with acute myeloi d leukaemia (AML) and 10 haematologically normal controls. Patterns di ffering from those of the haemopoietic cell line TF-1 were detected in 25/35 (71%) AML patients and 8/10 (80%) normal controls. A total of s ix base substitutions were identified by sequencing. Three were conser vative for the amino acid involved, three led to amino acid difference s, valine(652)--> methionine, glycine(647)--> valine and proline(603)- -> threonine. One alteration was found only in a normal control, the o ther five were all found in both AML patients and normal controls sugg esting that they were DNA polymorphisms. Two substitutions were partic ularly common with allele frequencies of 0.23 (G(1972)--> A, unchanged proIine(648)) and 0.13 (C-1306--> T, unchanged serine(426)). These re sults indicate that the GM-CSFR beta(c) chain is highly polymorphic bu t point mutations of the intracytoplasmic tail do not appear to contri bute frequently to the pathogenesis of AML.