title: Cytogenetic and molecular genetic abnormalities in agnogenic myeloid metaplasia.
abstract: Agnogenic myeloid metaplasia (AMM), a clonal hematopoietic stem cell disorder also known as chronic idiopathic myelofibrosis, is characterized by a polyclonal, or reactive, stromal proliferation, resulting from the inappropriate release of megakaryocyte/monocyte-derived growth factors. Cytogenetic studies indicate that 30% of cases possess a clonal cytogenetic abnormality at diagnosis, a figure that increases to approximately 90% following leukemic transformation. Patients with specific abnormal karyotypes have a poor prognosis and may fail to respond to androgen therapy. The incidence of chromosomal abnormalities is significantly less in younger patients, a fact that may explain their more favorable prognosis. Common findings include 13q-, 20q-, trisomy 8, and abnormalities of chromosomes 1, 7, and 9. However, detailed cytogenetic analysis has not yet led to the identification of pathogenetically relevant genes and, as a result, the molecular mechanisms responsible for the clonal proliferation remain unknown. Targeted gene screening has revealed only rare oncogenic point mutations in N-RAS, p53, and c-KIT.
authors.affiliation: Academic Unit of Haematology, Henry Wellcome Laboratories for Medical Research, Sheffield, UK. j.t.reilly@sheffield.ac.uk
authors.forename: John T
authors.initials: JT
authors.lastname: Reilly
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002869:Chromosome Aberrations; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D006801:Humans; D007621:Karyotyping; D055728:Primary Myelofibrosis / Q000235:genetics*