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Localisation and distribution of hyaluronan in normal bone marrow matrix: a novel method to evaluate impending fibrosis?
Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
2002 (English)In: European Journal of Haematology, ISSN 0902-4441, Vol. 68, no 4, 194-202 p.Article in journal (Refereed) Published
Abstract [en]

Bone marrow trephine biopsies from 30 healthy volunteers, 10 men and 20 women aged 18-60 yr were obtained for identification and localisation of hyaluronan (HYA). Fixation, decalcification and embedding were performed by two different methods, with identical results in both. For comparison bone marrow trephine biopsies from three patients with different haematological diseases and known fibrosis were studied. All bone marrow specimens were also stained for reticulin grading. HYA was found in the bone marrow specimens from healthy individuals in a pattern that was concordant with the reticulin staining, the common way of visualising bone marrow fibrosis. In bone marrow from the patients with known fibrosis the HYA and reticulin staining were both more intense and abundant. Interestingly, HYA was also found intracellularly in eosinophilic cells in normal bone marrow. HYA is a polysaccharide unique both in structural and biological properties, and in excess it may predict bone marrow fibrosis.

Place, publisher, year, edition, pages
2002. Vol. 68, no 4, 194-202 p.
URN: urn:nbn:se:umu:diva-4875DOI: 10.1034/j.1600-0609.2002.01617.xPubMedID: 12071934OAI: diva2:144142
Available from: 2005-12-15 Created: 2005-12-15Bibliographically approved
In thesis
1. Hyaluronan in normal and malignant bone marrow: a clinical and morphological study with emphasis on myelofibrosis
Open this publication in new window or tab >>Hyaluronan in normal and malignant bone marrow: a clinical and morphological study with emphasis on myelofibrosis
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Fibrosis in the bone marrow is usually denominated myelofibrosis and may contribute to impaired hematopoiesis. Myelofibrosis is seen both in malignant and non-malignant diseases.

The normal microenvironment in the bone marrow consists of a heterogenous population of hematopoietic and non-hematopoietic stromal cells, their extracellular products and hematopoietic cytokines. The stromal cells produce a complex array of molecules, among others collagens and glycosaminoglycans (GAGs) of which hyaluronan (HYA) is the most abundant. Marrow fibrosis results from an increased deposition of collagens, which are polypeptides. Staining for reticulin, mostly composed of collagen type III, is the common way of visualizing myelofibrosis. HYA, like the collagens, is widely distributed in connective tissues. Little is known about the distribution of HYA in bone marrow.

The aims of this thesis have been to determine how HYA is distributed in normal and malignant bone marrow, compared to reticulin staining, and to follow patients with chronic myeloproliferative diseases (CMPD) during two years treatment with anagrelide considering development of cellularity and fibrosis.

In bone marrow biopsies from healthy volunteers, the controls, HYA was found in a pattern that was concordant with the reticulin staining.

Comparing patients with different malignant diseases with and without bone marrow involvemen, HYA staining was found to be significantly stronger in both groups compared to the controls.

The HYA scores were also significantly higher in the bone marrow of patients with de novo acute myeloid leukemia (AML), compared to the controls.

There was a correlation between HYA and reticulin in the patients with de novo AML, and in the patients with different malignant diseases with and without bone marrow involvement as in the controls.

Increase of HYA, reticulin and cellularity in the bone marrow of patients with CMPD after two years of treatment with anagrelide indicated progression of fibrosis. Anagrelide is a valuable drug for reduction of platelets but seems unable to stop progression of fibrosis and hypercellularity.

HYA is an interesting molecule with properties not only contributing to the structure of extracellular matrix but also to cell signaling and behaviour, although the understanding of the detailed mechanisms is still incomplete.

Place, publisher, year, edition, pages
Umeå: Folkhälsa och klinisk medicin, 2005. 60 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 997
Hyaluronan, reticulin, fibrosis, chronic myeloproliferative disorders, acute myeloid leukemia, anagrelide, bone marrow
National Category
Clinical Science
urn:nbn:se:umu:diva-658 (URN)91-7305-990-0 (ISBN)
Public defence
2006-02-03, Sal D, Tandläkarhögskolan, Norrlands Universitetssjukhus, Umeå, 13:00 (English)
Available from: 2005-12-15 Created: 2005-12-15 Last updated: 2009-10-08Bibliographically approved

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