FMS mutations in myelodysplastic, leukemic, and normal subjects

Journal Article · Thu Feb 01 04:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.4.1377· OSTI ID:6073709

Ridge, S A; Worwood, M; Jacobs, A; Padua, R A ^[1]; Oscier, D ^[2]

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1. Univ. of Wales College of Medicine (England)
2. Royal Victoria Hospital, Bournemouth (England)

The FMS gene encodes the functional cell surface receptor for colony-stimulating factor 1, the macrophage-and monocyte-specific growth factor. Codons 969 and 301 have been identified as potentially involved in promoting the transforming activity of FMS. Mutations at codon 301 are believed to lead to neoplastic transformation by ligand independence and constitutive tyrosine kinase activity of the receptor. The tyrosine residue at codon 969 has been shown to be involved in a negative regulatory activity, which is disrupted by amino acid substitutions. This study reports on the frequency of point mutations at these codons, in vivo, in human myeloid malignancies and in normal subjects. We studied 110 patients (67 with myelodysplasia (MDS) and 48 with acute myeloblastic leukemia (AML)), 5 patients being studied at the MDS and the later AML stage of the disease. There was a total incidence of 12.7% (14/110) with mutations in codon 969 and 1.8% (2/110) with mutations in codon 301. Two patients had mutations in the AML stage of the disease but not in the preceding MDS and one had a mutation in the MDS stage but not upon transformation of AML. This is consistent with the somatic origin of these mutations. FMS mutations were most prevalent (20%) in chronic myelomonocytic leukemia and AML type M4 (23%), both of which are characterized by monocytic differentiation. One of 51 normal subjects had a constitutional codon 969 mutation, which may represent a marker for predisposition to myeloid malignancy.

• OSTI ID: 6073709
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:4; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
CARCINOGENESIS
CELL TRANSFORMATIONS
CLONING
CODONS
CONNECTIVE TISSUE CELLS
DISEASES
DNA HYBRIDIZATION
DNA POLYMERASES
DNA SEQUENCING
DNA-CLONING
ENZYMES
GENE MUTATIONS
GROWTH FACTORS
HEMIC DISEASES
HYBRIDIZATION
HYDROXY ACIDS
IMMUNE SYSTEM DISEASES
LEUKEMIA
LEUKOCYTES
MACROPHAGES
MATERIALS
MEMBRANE PROTEINS
MITOGENS
MONOCYTES
MUTATION FREQUENCY
MUTATIONS
NEOPLASMS
NUCLEOTIDYLTRANSFERASES
ONCOGENIC TRANSFORMATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PATHOGENESIS
PATIENTS
PHAGOCYTES
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
PROTEINS
RECEPTORS
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
TRANSFERASES
TUMOR CELLS
TYROSINE