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 ␤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 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). (Blood. 2003;101:4982-4989)

Pharmacogenomic Approach of Telomerase in Cancer: Importance of End Zone Variability

“…Aging of leukocytes reflected by short telomere length may impair immune surveillance and reduce the clearance of tumor cells. A study demonstrated that patients with multiple myeloma with high telomerase activity and short telomere length presented a poor prognosis (Wu, Orme et al 2003). Accordingly, another study reports the same results in adult T-cell leukemia, suggesting that telomerase www.intechopen.com activity and low telomere content may be novel markers for the prognosis of these diseases (Kubuki, Suzuki et al 2005).…”

Prediagnostic telomere length and risk of B-cell lymphoma-Results from the EPIC cohort study

“…24 The only prospective study evaluating lymphoma risk in relation to TL 23 suggested that individuals with relatively longer telomeres have an elevated NHL risk which is inconsistent with the results of previous case-control studies. 22,25 As such, the finding in the prospective cohort study deserves further follow-up to see if these findings can be corroborated in an independent study.…”

“…case-control studies among MM (n 5 183) 25 and CLL patients (n 5 70) 35 did not show significant TL differences between patients and healthy controls. These studies were limited by small control groups (seven MM studies and 15 CLL studies) and possibly confounded by the inclusion of pretreated patient subgroups (MM study).…”

Telomere dysfunction and its role in haematological cancer

“…TL in MM cells has been shown to be reduced compared to patient-matched leucocytes and normal age-matched controls, and was shorter still in patients with relapsed disease (Cottliar et al, 2003;Wu et al, 2003). In addition, there appears to be a stabilization of telomeres in the shorter length ranges below 5AE5 kb.…”