title: Dysregulation and overexpression of HMGA2 in myelofibrosis with myeloid metaplasia.
abstract: Among cytogenetic studies of patients affected with myelofibrosis with myeloid metaplasia (MMM), a rare chronic myeloproliferative disorder, we found several reports of structural abnormalities of the long arm of chromosome 12. Two MMM patients had a balanced translocation involving 12q: t(4;12)(q32;q15) and t(5;12)(p14;q15), respectively. FISH (fluorescence in situ hybridization) analysis showed that BAC (bacterial artificial chromosome) RP11-366L20 overlaps the breakpoint in both cases. A gene, HMGA2, most of which is included in that BAC, thus was identified as a potential candidate. Using reserves transcriptase-polymerase chain reaction (RT-PCR), we looked for expression of HMGA2 in blood mononuclear cells from these 2 patients and demonstrated a transcript in both. Moreover, we found the gene expressed in the hematopoietic cells of 10 of 10 additional patients bearing no 12q anomalies. HMGA2, not expressed in normal subjects, is implicated in benign solid tumors such as lipomas, leiomyomas, and other rare tumors of mesenchymal origin. We postulate that its dysregulation and overexpression in myeloid progenitors contribute also to the pathogenesis of MMM.
authors: INSERM Unité 524, Institut de Recherche sur le Cancer de Lille, Lille, France. j-andrieux@chru-lille.fr
authors: Joris
authors: J
authors: Andrieux
authors: Jean-Loup
authors: JL
authors: Demory
authors: Brigitte
authors: B
authors: Dupriez
authors: Sabine
authors: S
authors: Quief
authors: Isabelle
authors: I
authors: Plantier
authors: Christophe
authors: C
authors: Roumier
authors: Francis
authors: F
authors: Bauters
authors: Jean Luc
authors: JL
authors: Laï
authors: Jean-Pierre
authors: JP
authors: Kerckaert
mesh_terms: D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D025743:HMGA2 Protein / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D055728:Primary Myelofibrosis / Q000235:genetics*
chemical_list: D025743:HMGA2 Protein