Related Experiment Video
Updated: Jun 21, 2026
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
Identification of new target molecules PTK2, TGFBR2 and CD9 overexpressed during advanced bone marrow remodelling in
Oliver Bock1, Michaela Muth, Katharina Theophile
1Institute of Pathology, Hannover Medical School, Hannover, Germany. Bock.Oliver@MH-Hannover.de
Abstract:
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 < or = 0.01) three candidates, PTK2 protein tyrosine kinase 2 (PTK2), transforming growth factor beta 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 < or = 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.
Insights
Primary myelofibrosis (PMF) involves bone marrow remodeling. New research identifies PTK2, TGFBR2, and CD9 as key molecules in advanced PMF, offering potential targets for therapy.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Primary myelofibrosis (PMF) is a myeloproliferative neoplasm causing bone marrow fibrosis and angiogenesis.
- Advanced PMF presents a dense fibrotic meshwork, hindering cellular analysis.
- Gene expression related to stromal pathology in advanced PMF is not well understood.
Purpose of the Study:
- To investigate gene expression profiles in bone marrow biopsies from PMF patients.
- To identify novel molecular targets involved in bone marrow remodeling in PMF.
Main Methods:
- Utilized custom low-density arrays (LDA) to analyze gene expression in PMF bone marrow biopsies.
- Focused on genes involved in extracellular matrix synthesis, remodeling, cellular adhesion, and motility.
- Validated key gene candidates (PTK2, TGFBR2, CD9) in a larger cohort.
Main Results:
- Identified 11 genes upregulated in advanced PMF stages.
- PTK2 (protein tyrosine kinase 2), TGFBR2 (transforming growth factor beta type II receptor), and CD9 (CD9 molecule) were significantly overexpressed in advanced PMF.
- Endothelial cells and activated fibroblasts were identified as major sources of PTK2, TGFBR2, and CD9.
Conclusions:
- PTK2, TGFBR2, and CD9 are newly identified molecular targets in PMF bone marrow remodeling.
- These molecules warrant further investigation for their potential in targeted therapy for PMF.
