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Prepublished online as a Blood First Edition Paper on February 27, 2003; DOI 10.1182/blood-2002-11-3451.
Submitted November 19, 2002
Accepted February 12, 2003
Telomerase and telomere length in multiple myeloma: correlations with disease heterogeneity, cytogenetic status and overall survival
Kai-Da Wu, Lisa M Orme, John Shaughnessy, Joth Jacobson, Bart Barlogie, and Malcolm A S Moore*
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Cancer Research and Biostatistics, Seattle, WA, USA
* Corresponding author; email: m-moore{at}ski.mskcc.org.
We have investigated the significance of telomerase activity (TA) and telomere length (TL) in multiple myeloma (MM). The analyses were undertaken on CD138+ MM cells isolated from the marrow of 183 patients either at diagnosis or in relapse. There was heterogeneity in telomerase expression with 36% having TA comparable to the activity detected in normal plasma cells and 13% having levels 1-4 fold greater than in a neuroblastoma cell line control. The TL of MM cells was significantly shorter than that of the patients' own leukocytes, with 25% of cases having a TL of <4.0kbp. Analysis of TL distribution indicated selective TA-mediated stabilization of shorter telomeres when mean TL fell below 5.5kbp. Unusually long telomeres were observed in seven cases (10.8-15.0 kbp) with low TA in 5/7, suggesting the operation of a TA-independent pathway of telomere stabilization. There was a strong negative correlation between TA and TL or platelet count. TL negatively correlated with age and with IL-6 and  2-microglobulin levels. Various cytogenetic abnormalities, including those associated with poor prognosis, strongly correlated with TA and to a lesser extent with short TL. High TA and short TL defined a subgroup of patients with poor prognosis. At one year there was an 82% survival in patients with TA of <25% of neuroblastoma control and a TL of >5.5 kbp versus a 63% survival in patients with higher TA and shorter TL (P=.004). The two-year survival of patients with a TA of <25% was 81% versus 52% in those with a higher TA (P<.0001).
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