Loss of both CSF1R (FMS) alleles in patients with myelodysplasia and a chromosome 5 deletion

Journal Article · Mon Jul 15 04:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.14.6176· OSTI ID:5933390

Boultwood, J; Rack, K; Buckle, V J; Wainscoat, J S ^[1]; Kelly, S ^[2]; Madden, J; Oscier, D G ^[3]; Sakaguchi, A Y; Wang, Lingmei ^[4]

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1. John Radcliffe Hospital, Oxford (England)
2. Wycombe General Hospital, High Wycombe, (England)
3. Royal Victoria Hospital, Boscombe (England)
4. Univ. of Texas Health Science Center, San Antonio (United States)

A high proportion of patients with myelodysplasia show characteristic karyotypic abnormalities in bone marrow cells. The most distinctive of the myelodysplastic syndromes is the 5q- syndrome characterized by refractory anemia, poorly lobulated megakaryocytes, and an interstitial deletion of the long arm of chromosome 5 (5q deletion) as the sole karyotypic abnormality. Recently, several genes encoding hemopoietic growth factors and receptors, have been localized to the long arm of chromosome 5, and there has been much speculation that deletion of one or more of these genes may be critical to the pathogenesis of the associated myeloid disorders. One candidate gene is CSF1R. The authors have carried out a molecular examination of the CSF1R, both on the 5q- chromosome and on the apparently normal homologous chromsome 5, in 10 patients with myelodysplasia and a 5q deletion. They have found, using restriction fragment length polymorphism analysis and gene dosage experiments, that all 10 patients showed deletion of CSF1R. The homozygous CSF1R loss has been confirmed in 2 patients by an in situ hybridization technique comparing the signal in affected cells to that in control sex-mismatched cells on the same slides. This loss of one CSF1R allele, together with loss in some cells of the remaining allele on the homologous chromsome 5, in patients with myelodysplasia indicates that this is a region of critical gene loss on 5q. The loss of the hemopoietic growth factor receptor gene CSF1R may be important in the pathogenesis of human myeloid leukemia.

• OSTI ID: 5933390
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:14; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
BONE MARROW CELLS
CARCINOGENESIS
CHROMOSOMAL ABERRATIONS
CHROMOSOMES
CONNECTIVE TISSUE CELLS
DISEASES
DNA HYBRIDIZATION
GROWTH FACTORS
HUMAN CHROMOSOME 5
HUMAN CHROMOSOMES
HYBRIDIZATION
IMMUNE SYSTEM DISEASES
KARYOTYPE
LEUKEMIA
LEUKEMOGENESIS
MITOGENS
MOLECULAR BIOLOGY
MUTATIONS
MYELOID LEUKEMIA
NEOPLASMS
ORGANIC COMPOUNDS
PATHOGENESIS
PATIENTS
PROTEINS
SOMATIC CELLS