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Prepublished online as a Blood First Edition Paper on June 7, 2002; DOI 10.1182/blood-2002-01-0030.

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2002-01-0030v1
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Submitted January 4, 2002
Accepted May 13, 2002

Characterization of hyaluronan synthase expression and hyaluronan synthesis in bone marrow mesenchymal progenitor cells: predominant expression of HAS1 mRNA and upregulated hyaluronan synthesis in bone marrow cells derived from multiple myeloma patients

Anthony Calabro, Martin M Oken, Vincent C Hascall, and Anna M Masellis*

Department of Biomedical Engineering, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, USA
Leukemia Research, Abbott Northwestern Hospital, Virginia Piper Cancer Institute, Minneapolis, MN, USA

* Corresponding author; email: anna.masellis{at}allina.com.

Hyaluronan (HA) is suggested to play a role in the pathophysiology of multiple myeloma. To further investigate the role of HA in this disease, we examined hyaluronan synthase (Has) gene expression and HA production in bone marrow mesenchymal progenitor cells (bmMPCs) derived from multiple myeloma patients. The relative abundance of mRNA for each HAS gene was determined using competitive reverse transcription polymerase chain reaction (cRt-PCR), while HA production was detected by fluorophore-assisted carbohydrate electrophoresis (FACE). We determined the basal expression of Has isoforms in myeloma bmMPCs and then compared this expression to expression in normal donor bmMPCs. Of the three Has isoforms, Has1 mRNA was predominantly expressed in myeloma bmMPCs, with expression 7.6 fold greater than Has2. In comparison to normal bmMPCs, Has1 mRNA expression was 20 fold greater in myeloma bmMPCs. Normal bmMPCs predominantly expressed Has2 mRNA (8.2 fold greater than myeloma bmMPCs). Upon co-culture of myeloma bmMPCs with plasma cells, Has1 transcript was strongly attenuated. FACE results show that myeloma bmMPCs synthesize 5.7 fold more HA than those from normal donors. These data suggest that myeloma bmMPCs could be an important component of the myeloma pathophysiology in vivo by their increased expression of ECM components relevant to plasma cell growth and survival.


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