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Here we studied the expression of the major extracellular matrix proteins of fibrosis in relation to diagnostic silver grading supported by image analysis. Methods and Results By using automated immunohistochemistry, here we demonstrate, that the expression of both type-I and type-III collagens, and fibrillin-1 by bone marrow stromal cells can reveal the extracellular matrix scaffolding in line with myelofibrosis progression as classified by silver grading. ?Reticulin? fibrosis indicated by type-III collagen expression and ?collagen? fibrosis featured by type-I collagen expression were parallel rather than sequential events. This is line with the proposed role of type-III collagen in regulating type-I collagen fibrillogenesis. The uniformly strong firbillin-1 immune signals offered the best interrater agreements and the highest statistical correlations with silver grading of the 3 markers, which was robustly confirmed by automated whole slide digital image analysis using a machine learning-based algorithm. The progressive upregulation of fibrillin-1 during myelofibrosis may result from a negative feedback loop since fibrillin microfibrils sequester TGF-? the major promoter of fibrosis. This can also reduce TGF-? induced RANKL levels which would stimulate osteoclastogenesis and thus can support osteosclerosis in advanced myelofibrosis. Conclusions Through the in situ detection of these extracellular matrix proteins our results verify the molecular pathobiology of fibrosis during myelofibrosis progression. 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