Analysis of the granulocyte colony-stimulating factor receptor gene structure using PCR-SSCP in myeloid leukemia and myelodysplastic syndrome.

The membrane-proximal cytoplasmic region of the granulocyte colony-stimulating factor receptor (G-CSFR) is known to be essential for the proliferation signal, with a more distal region being required for the differentiation signal. Such a separation of functional domains raises the possibility that mutations occurring at these regions may contribute to cell proliferation in the absence of differentiation, this being the most important characteristic in acute leukemia cells. Therefore, we analysed the structural abnormalities at the transmembrane and cytoplasmic region of G-CSFR in a significant number of patients with various myeloid malignancies. When we examined the genomic DNA of G-CSFR obtained from 41 patients with acute myelogenous leukemia (AML), 18 with chronic myelogenous leukemia (CML), 7 with myelodysplastic syndrome (MDS), 2 with chronic myelomonocytic leukemia and 1 with chronic neutrophilic leukemia, we found a polymorphism in 3 patients, but no significant pathogenic mutations in any patients. The screening for this polymorphism in 100 hematologically normal controls revealed that it may be useful as a linkage marker for population and family studies, because the heterozygosity index is at a high level (0.055). While there have been several reports discussing the leukemogenic potential of mutations in the cytokine/hematopoietin receptor superfamily, genetic alterations in the transmembrane and cytoplasmic region of G-CSFR do not seem to play a pathogenic role in leukemia.