title: Bone morphogenetic protein antagonist gene NOG is involved in myeloproliferative disease associated with myelofibrosis.
abstract: In a case with secondary myelofibrosis occurring after essential thrombocythemia, cytogenetic analysis revealed an isolated translocation t(X;17)(q27;q22) in all cells. We found that a bacterial artificial chromosome (BAC) encompassing the breakpoint on chromosome 17 long arm contained only one gene, NOG. We therefore investigated the occurrence of this rare breakpoint in myeloproliferative disorders (MPDs). We identified three more patients with a 17q abnormality in MPDs: myelofibrosis with myeloid metaplasia (MMM); chronic myeloid leukemia positive for t(9;22)(q34;q11) with additional t(4;17)(p15;q22) at diagnosis; and myelofibrosis complicating polycythemia vera. All three cases exhibited a split of BACs containing NOG. The protein encoded by NOG, noggin, acts as an antagonist to bone morphogenetic secreted protein 2 and 4 (BMP2 and BMP4). A comparative analysis of gene expression on Agilent 22K oligonucleotide microarrays in purified CD34+ cells from the blood of MMM patients showed significant downregulation of BMPR2, BMPR1B, BMP2, and BMP8; upregulation of BMP3 and BMP10; and a trend to lower expression of NOG. Thus, given that expression and release of BMPs are important in the induction of osteosclerosis and angiogenic activity, the observed BMP deregulations could be triggered by potential NOG genetic alterations in the four cases here described, and may contribute to the myelofibrotic process characterized by bone marrow stromal reaction including collagen fibrosis, osteosclerosis, and angiogenesis.
authors: Medical Genetics Laboratory, Jeanne de Flandre Hospital, CHRU, 2 Avenue Oscar Lambret, 59037 Lille, France. j-andrieux@chru-lille.fr
authors: Joris
authors: J
authors: Andrieux
authors: Catherine
authors: C
authors: Roche-Lestienne
authors: Sandrine
authors: S
authors: Geffroy
authors: Christophe
authors: C
authors: Desterke
authors: Nathalie
authors: N
authors: Grardel
authors: Isabelle
authors: I
authors: Plantier
authors: Dominik
authors: D
authors: Selleslag
authors: Jean-Loup
authors: JL
authors: Demory
authors: Jean-Luc
authors: JL
authors: Laï
authors: Xavier
authors: X
authors: Leleu
authors: Caroline
authors: C
authors: Le Bousse-Kerdiles
authors: Peter
authors: P
authors: Vandenberghe
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D002352:Carrier Proteins / Q000502:physiology*; D002886:Chromosomes, Human, Pair 17; D041321:Chromosomes, Human, X; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000235:genetics*; D010026:Osteosclerosis / Q000235:genetics; D055728:Primary Myelofibrosis / Q000235:genetics*; D014178:Translocation, Genetic; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000099176:Noggin Protein