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Blood, 15 August 2004, Vol. 104, No. 4, pp. 1151-1158. Prepublished online as a Blood First Edition Paper on April 22, 2004; DOI 10.1182/blood-2003-11-4079. This Article Full Text (PDF) All Versions of this Article: 2003-11-4079v1 104/4/1151    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Maxwell, C. A Articles by Reiman, T. Search for Related Content PubMed PubMed Citation Articles by Maxwell, C. A Articles by Reiman, T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 1, 2003 Accepted April 13, 2004 RHAMM expression and isoform balance predicts aggressive disease and poor survival in multiple myeloma Christopher A Maxwell, Erik Rasmussen, Fenghuang Zhan, Jonathan J Keats, Sophia Adamia, Erin Strachan, Mary Crainie, Ronald Walker, Andrew R Belch, Linda M Pilarski, Bart Barlogie, John Shaughnessy, and Tony Reiman* Oncology and Medicine, University of Alberta & Cross Cancer Institute, Edmonton, Alberta, Canada Donna and Donald Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA * Corresponding author; email: tonyreim{at}cancerboard.ab.ca. Multiple myeloma (MM) plasma cells (PC) express RHAMM, a hyaluronan binding, cytoskeleton and centrosome protein. The most abundant RHAMM isoforms in MM are full-length RHAMMFL and the splice variant RHAMM-exon4. We separately examined the significance of RHAMM expression, and isoform balance, in two groups of MM patients. In oligonucleotide microarray experiments (n=210, Arkansas), increasing RHAMM mRNA expression in MM PC is strongly associated with osteolytic bone lesions (p<0.001), event-free (p=0.05) and overall survival (p=0.04). Semiquantitative determination of RHAMM isoform expression (Alberta, Canada) utilized capillary electrophoretic detection and measurement of RHAMM-exon4/RHAMMFL RT-PCR products. RHAMM isoforms are rarely expressed concurrently in single MM PC; the pattern of isoform expression, at the single cell level, is approximated in larger numbers of cells by the RHAMM-exon4/ RHAMMFL ratio. Absolute RHAMM expression and the RHAMM-exon4/ RHAMMFL ratio are only partially correlated in MM PC; in cell lines, absolute RHAMM expression is elevated in mitosis while RHAMM ratios remain stable. Temporal examination of MM patients peripheral blood reveals that the RHAMM-exon4/RHAMMFL ratio increases with disease burden. The RHAMM-exon4/RHAMMFL ratio in diagnostic bone marrow samples (n=101, Alberta) is an independent prognostic factor. Thus, expression and splicing of RHAMM are important molecular determinants of disease severity in MM. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Population dynamics and clonal dominance in tumors? Eva A. Turley and James B. McCarthy Blood 2004 104: 909-910. [Full Text] [PDF] This article has been cited by other articles: A. Ghosh, H. Kuppusamy, and L. M. Pilarski Aberrant Splice Variants of HAS1 (Hyaluronan Synthase 1) Multimerize with and Modulate Normally Spliced HAS1 Protein: A POTENTIAL MECHANISM PROMOTING HUMAN CANCER J. Biol. Chem., July 10, 2009; 284(28): 18840 - 18850. [Abstract] [Full Text] [PDF] P. Kaestner, A. Stolz, and H. Bastians Determinants for the efficiency of anticancer drugs targeting either Aurora-A or Aurora-B kinases in human colon carcinoma cells Mol. Cancer Ther., July 1, 2009; 8(7): 2046 - 2056. [Abstract] [Full Text] [PDF] S. Adamia, A. A. Reichert, H. Kuppusamy, J. Kriangkum, A. Ghosh, J. J. Hodges, P. M. Pilarski, S. P. Treon, M. J. Mant, T. Reiman, et al. Inherited and acquired variations in the hyaluronan synthase 1 (HAS1) gene may contribute to disease progression in multiple myeloma and Waldenstrom macroglobulinemia Blood, December 15, 2008; 112(13): 5111 - 5121. [Abstract] [Full Text] [PDF] J. P. Venables, R. Klinck, A. Bramard, L. Inkel, G. Dufresne-Martin, C. Koh, J. Gervais-Bird, E. Lapointe, U. Froehlich, M. Durand, et al. Identification of Alternative Splicing Markers for Breast Cancer Cancer Res., November 15, 2008; 68(22): 9525 - 9531. [Abstract] [Full Text] [PDF] C. A. Maxwell, J. McCarthy, and E. Turley Cell-surface and mitotic-spindle RHAMM: moonlighting or dual oncogenic functions? J. Cell Sci., April 1, 2008; 121(7): 925 - 932. [Abstract] [Full Text] [PDF] Y. Shi, T. Reiman, W. Li, C. A. Maxwell, S. Sen, L. Pilarski, T. R. Daniels, M. L. Penichet, R. Feldman, and A. Lichtenstein Targeting aurora kinases as therapy in multiple myeloma Blood, May 1, 2007; 109(9): 3915 - 3921. [Abstract] [Full Text] [PDF] J. Greiner, M. Schmitt, L. Li, K. Giannopoulos, K. Bosch, A. Schmitt, K. Dohner, R. F. Schlenk, J. R. Pollack, H. Dohner, et al. Expression of tumor-associated antigens in acute myeloid leukemia: implications for specific immunotherapeutic approaches Blood, December 15, 2006; 108(13): 4109 - 4117. [Abstract] [Full Text] [PDF] C. A. Maxwell, J. J. Keats, A. R. Belch, L. M. Pilarski, and T. Reiman Receptor for Hyaluronan-Mediated Motility Correlates with Centrosome Abnormalities in Multiple Myeloma and Maintains Mitotic Integrity Cancer Res., February 1, 2005; 65(3): 850 - 860. [Abstract] [Full Text] [PDF]

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