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Identification of new target molecules PTK2 , TGFBR2 and CD9 overexpressed during advanced bone marrow remodelling in primary myelofibrosis
Author(s) -
Bock Oliver,
Muth Michaela,
Theophile Katharina,
Winter Melissa,
Hussein Kais,
Büsche Guntram,
Kröger Nicolaus,
Kreipe Hans
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07808.x
Subject(s) - myelofibrosis , bone marrow , stromal cell , ptk2 , cancer research , myeloproliferative neoplasm , pathology , extracellular matrix , medicine , biology , receptor , microbiology and biotechnology , growth factor , platelet derived growth factor receptor
Summary Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by remodelling of the bone marrow, including progressive myelofibrosis and exaggerated angiogenesis. Advanced PMF frequently shows a full‐blown fibre meshwork, which avoids aspiration of cells, and the expression profile of genes related to stroma pathology at this stage remains largely undetermined. We investigated bone marrow core biopsies in PMF showing various degrees of myelofibrosis by custom‐made low density arrays (LDA) representing target genes with designated roles in synthesis of extracellular matrix, matrix remodelling, cellular adhesion and motility. Among a set of 11 genes up‐regulated in advanced stages of PMF ( P ≤ 0·01) three candidates, PTK2 protein tyrosine kinase 2 ( PTK2 ), transforming growth factor β type II receptor ( TGFBR2 ) and motility‐related protein‐1 (CD9 molecule, CD9 ), were investigated in more detail. PTK2 , TGFBR2 and CD9 were significantly overexpressed in larger series of advanced PMF stages ( P ≤ 0·01 respectively). Endothelial cells of the increased microvessel network in PMF could be identified as a predominant source for PTK2 , TGFBR2 and CD9 . CD9 also strongly identified activated fibroblasts in advanced myelofibrosis. We conclude that PTK2 , TGFBR2 and CD9 represent new target molecules involved in bone marrow remodelling of PMF and warrant further investigation for potential targeted therapy.