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Increased telomerase activity is associated with shorter survival in patients with chronic phase chronic myeloid leukemia
Authors:Verstovsek Srdan  Kantarjian Hagop  Manshouri Taghi  Cortes Jorge  Faderl Stefan  Giles Francis J  Keating Michael  Albitar Maher
Affiliation:Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Abstract:BACKGROUND: Significantly elevated telomerase activity (TA) has been found in samples from patients with many malignant hematologic diseases. However, the impact of elevated TA on the course of patients with chronic phase chronic myeloid leukemia (CP-CML) is unknown. METHODS: Using a modified polymerase chain reaction-based telomeric repeat amplification protocol assay, the authors measured TA in bone marrow samples from 93 patients with CP-CML and correlated it with patient characteristics and survival. TA also was measured in bone marrow samples from 29 patients with accelerated/blastic phase CML. RESULTS: Patients with accelerated/blastic phase CML were found to have somewhat higher levels of TA compared with patients with CP-CML (P = 0.07). Among patients with CP-CML, those with high TA progressed to advanced stages of disease sooner (P = 0.05) and had a significantly shorter survival (P = 0.04) than patients with low TA. No correlation was found between TA and patient age, hemoglobin, platelet and leukocyte counts, percentage of peripheral or bone marrow blasts or basophils, or bone marrow cellularity. On multivariate analysis, high TA retained its significance as a factor associated with shorter patient survival (P = 0.02). CONCLUSIONS: The current study data suggest that TA plays a role in the propagation of CP-CML and that the potential of telomerase inhibitors in patients with CML should be explored, even in those with early phase disease.
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