title: Cytogenetic and molecular genetic aspects of idiopathic myelofibrosis.
abstract: Idiopathic myelofibrosis is a chronic myeloproliferative disorder in which the characteristic fibroblast proliferation is thought to be a secondary phenomenon resulting from the inappropriate release of megakaryocyte- and/or monocyte-derived growth factors, including PDGF, TGF-beta, bFGF and calmodulin. In contrast, the haematopoietic cells are clonal, although the underlying pathogenetic mechanisms remain essentially unknown. Cytogenetic studies have highlighted that 13q-, 20q-, +8 and abnormalities of chromosomes 1, 7 and 9 constitute more than 80% of the chromosomal changes. A third of idiopathic myelofibrosis cases have abnormal karyotypes at diagnosis, a figure that increases if follow-up analyses are performed. Evolution to more complex karyotypes may accompany clinical progression, with abnormalities increasing to around 90% following acute leukaemic transformation. Cytogenetic abnormalities have been associated with prognosis and to a lack of treatment response to androgens. Oncogene mutations are rare and include point mutations in N-RAS, c-KIT and TP53.
authors.affiliation: Academic Unit of Haematology, Division of Genomic Medicine, Royal Hallamshire Hospital, Sheffield, UK. j.t.reilly@sheffield.ac.uk
authors.forename: John T
authors.initials: JT
authors.lastname: Reilly
mesh_terms: D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D002882:Chromosomes, Human, Pair 13; D002890:Chromosomes, Human, Pair 20; D002898:Chromosomes, Human, Pair 8; D006801:Humans; D055728:Primary Myelofibrosis / Q000235:genetics*; D014314:Trisomy