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RHAMM expression and isoform balance predict aggressive disease and poor survival in multiple myeloma

Christopher A Maxwell1, Erik Rasmussen, Fenghuang Zhan

  • 1Department of Medical Oncology, Cross Cancer Institute, 11560 University Ave, Edmonton, AB, T6G 1Z2, Canada.

Blood
|April 24, 2004
PubMed

Insights

Receptor for hyaluronan-mediated motility (RHAMM) expression and splicing in multiple myeloma (MM) plasma cells are linked to disease severity. Higher RHAMM mRNA correlates with bone lesions and poorer survival, while the RHAMM-exon4/RHAMMFL ratio predicts prognosis.

Area of Science:

  • Molecular biology
  • Oncology
  • Biochemistry

Background:

  • Multiple myeloma (MM) plasma cells express receptor for hyaluronan-mediated motility (RHAMM), a protein involved in cell motility.
  • Key RHAMM isoforms in MM include full-length RHAMM (RHAMMFL) and the splice variant RHAMM-exon4.
  • The clinical significance of RHAMM expression and isoform balance in MM requires further investigation.

Purpose of the Study:

  • To investigate the association between RHAMM expression levels and MM patient outcomes.
  • To determine the prognostic value of the RHAMM-exon4/RHAMMFL isoform ratio in MM.
  • To explore the relationship between RHAMM expression, splicing, and disease severity.

Main Methods:

  • Oligonucleotide microarrays were used to assess RHAMM mRNA expression in MM plasma cells (n=210).
  • Capillary electrophoresis and RT-PCR were employed to determine RHAMM-exon4/RHAMMFL ratios in MM patient samples (n=101).
  • Analysis included correlation with osteolytic bone lesions, survival data, disease burden, and diagnostic bone marrow samples.

Main Results:

  • Increased RHAMM mRNA expression in MM plasma cells strongly correlated with osteolytic bone lesions and reduced event-free and overall survival.
  • The RHAMM-exon4/RHAMMFL ratio, approximating single-cell isoform expression patterns, increased with disease burden.
  • The RHAMM-exon4/RHAMMFL ratio in diagnostic bone marrow samples was identified as an independent prognostic factor.

Conclusions:

  • RHAMM expression levels and isoform splicing are significant molecular determinants of multiple myeloma severity.
  • RHAMM mRNA levels and the RHAMM-exon4/RHAMMFL ratio offer valuable prognostic information for MM patients.
  • Further research into RHAMM's role could lead to novel therapeutic strategies for multiple myeloma.

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