Telomerase and telomere length in multiple myeloma: Correlations with disease heterogeneity, cytogenetic status, and overall survival Journal Article
| Authors: | Wu, K. D.; Orme, L. M.; Shaughnessy, J. Jr; Jacobson, J.; Barlogie, B.; Moore, M. A. S. |
| Article Title: | Telomerase and telomere length in multiple myeloma: Correlations with disease heterogeneity, cytogenetic status, and overall survival |
| Abstract: | 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; 36% of the patients had TA levels comparable to those detected in normal plasma cells, and 13% of patients had levels 1- to 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; in 25% of patients, the TL measured less than 4.0 kbp. Analysis of TL distribution indicated selective TA-mediated stabilization of shorter telomeres when mean TL fell below 5.5 kbp. Unusually long (10.8-15.0 kbp) telomeres were observed in 7 patients, and low TA was observed in 5 of 7 patients, suggesting the operation of a TA-independent pathway of telomere stabilization. A strong negative correlation existed between TA and TL or platelet count. TL negatively correlated with age and with interleukin-6 (IL-6) and β2-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 1 year the survival rate in patients with TA levels lower than 25% of neuroblastoma control and TL greater than 5.5 kbp was 82%, whereas in patients with higher TA and shorter TL the survival rate was 63% (P = .004). The 2-year survival rate for patients with TA levels lower than 25% was 81%, and it was 52% in those with higher TA levels (P < .0001). © 2003 by The American Society of Hematology. |
| Keywords: | adult; cancer survival; controlled study; protein expression; aged; aged, 80 and over; middle aged; survival rate; human cell; cancer recurrence; cancer patient; protein analysis; telomere; disease association; multiple myeloma; bone marrow; analytic method; cytogenetics; enzyme activity; telomerase; age; survival time; plasma cell; correlation analysis; neuroblastoma cell; membrane glycoproteins; cell isolation; interleukin 6; thrombocyte count; interleukin-6; aging; beta 2 microglobulin; bone marrow cell; chromosome aberrations; lymphocytes; chromosome analysis; leukocyte; cytogenetic analysis; plasma cells; genetic polymorphism; chromosomes, human, pair 13; chromosome size; granulocytes; proteoglycans; syndecan-1; syndecans; humans; prognosis; human; male; female; priority journal; article; beta 2-microglobulin |
| Journal Title: | Blood |
| Volume: | 101 |
| Issue: | 12 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2003-06-15 |
| Start Page: | 4982 |
| End Page: | 4989 |
| Language: | English |
| PUBMED: | 12609839 |
| PROVIDER: | scopus |
| DOI: | 10.1182/blood-2002-11-3451 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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