title: Refined chromosomal localization of the human thrombopoietin gene to 3q27-q28 and exclusion as the responsible gene for thrombocytosis in patients with rearrangements of 3q21 and 3q26.
abstract: Thrombocytosis is a characteristic clinical feature in patients with myelocytic malignancies and chromosomal rearrangements of 3q21 and 3q26, sometimes called the '3q21q26 syndrome'. The function of thrombopoietin (TPO) in megakaryocytopoiesis and thrombopoiesis as well as its chromosomal location, marked TPO as a candidate gene for malignancies with 3q rearrangements combined with dysmegakaryopoiesis. In this study 12 cases with inv(3)(q21q26) or t(3;3)(q21;q26) were analyzed by means of PFGE, but no rearrangements near the TPO locus were detectable. Six YACs containing the TPO locus were isolated and characterized. By dual color in situ hybridization using a YAC from 3q26 containing the EVI1 gene and a YAC from the TPO locus, the localization of the human TPO gene could be refined to 3q27-q28 about 15-20 Mbp telomeric to the 3q26 breakpoints occurring in myeloid malignancies. TPO levels were analyzed in the serum of three patients and were found to be in the normal range. These results confirm the findings of two previous studies that thrombopoietin expression is not the main cause of thrombocytosis in the 3q21q26 syndrome.
authors.affiliation: AG Tumorcytogenetik, Institut für Humangenetik der Medizinischen Universität zu Lübeck, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schnittger
authors.forename: F J
authors.initials: FJ
authors.lastname: de Sauvage
authors.forename: D
authors.initials: D
authors.lastname: Le Paslier
authors.forename: C
authors.initials: C
authors.lastname: Fonatsch
mesh_terms: D019457:Chromosome Breakage; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002893:Chromosomes, Human, Pair 3; D016521:Electrophoresis, Gel, Pulsed-Field; D005786:Gene Expression Regulation; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016133:Polymerase Chain Reaction; D013922:Thrombocytosis / Q000097:blood / Q000235:genetics*; D013926:Thrombopoietin / Q000097:blood / Q000235:genetics*
chemical_list: D013926:Thrombopoietin