Detection of Point Mutations Within the Macrophage Colony-Stimulating Factor Receptor Gene in Myelodysplastic Syndromes and Acute Myelomonocytic Leukemias

It is not yet clear to what extent growth factors and their corresponding receptors contribute to the escape of human leukemic cells from external growth control. The c-fms proto-oncogene encodes the receptor of the monocyte/ macrophage-specific growth factor M-CSF [1]. It is located on the long arm of chromosome 5 and deleted in the 5q−-syndrome [2]. In human acute myelomonocytic leukemia (AML) cells c-fms expression is reduced or missing and no aberrant transcripts have been detected [3, 4]. Gross structural changes could not be found by restriction fragment analysis [4]. The reduced c-fms expression is associated with a hypermethylation of the c-fms gene, indicating that it might be inactivated in AML blasts [5]. Gene products of v-fms differ from those of c-fms in their carboxy terminus. Forty amino acids of the “regular” receptor molecule are replaced by 11 unrelated amino acids.in the oncogene product [6, 7]. The alteration removes a single tyrosine residue in position 969 (Tyr969) which negatively regulates the response of the c-fms gene product to M-CSF stimulation [8, 9]. Recently, Ridge et al. [10] reported that point mutations within codon 969 occurred in myelodysplastic syndromes (MDS) and AML at a frequency of up to 13%.