hTERT, the catalytic component of telomerase, is downregulated in the haematopoietic stem cells of patients with chronic myeloid leukaemia.

Journal article

Telomere shortening is associated with disease progression in chronic myeloid leukaemia (CML). To investigate the biology and regulation of telomerase in CML, we evaluated expression of the telomerase components, its regulators and several telomeric-associated proteins. Quantitative real-time-polymerase chain reaction (PCR) was used to compare gene expression in the CD34+/leukaemic blast cells of 22 CML patient samples to the CD34+ cell population of healthy individuals. hTERT, the catalytic component of telomerase, was downregulated in eight of 12 chronic phase (CP) patients (P = 0.0387). Furthermore, hTERT was significantly downregulated in two of three patients in accelerated phase (AP) and seven of seven patients in blast crisis (BC), P = 0.0017. Expression of hTR and telomeric-associated proteins TEP1, TRF1, TRF2, tankyrase and PinX1 was high in the majority of CP and AP patients. With the exceptions of TEP1 and hTR, expression of these factors was highest in CP and decreased during disease progression. Expression of c-Myc, a positive regulator of hTERT transcription, correlated with hTERT expression and decreased with disease progression, falling below control levels in BC. hTERT levels were increased in CP patients following successful treatment with imatinib, relative to untreated CP patients. We suggest that reduced hTERT expression directly causes the shortened telomeres observed in CML.

Authors: Campbell, L; Fidler, C; Eagleton, H; Peniket, A; Kusec, R

• Publication status: Published
• Journal: Leukemia
• Volume: 20
• Issue: 4
• Pages: 671-679
• Publication date: 2006-04-01
• DOI: 10.1038/sj.leu.2404141
• EISSN: 1476-5551
• ISSN: 0887-6924
• Language: English
• Keywords: Proto-Oncogene Proteins c-myc; Telomerase; Reverse Transcriptase Polymerase Chain Reaction; Adolescent; Gene Expression Regulation, Enzymologic; Tankyrases; DNA-Binding Proteins; Pyrimidines; Telomeric Repeat Binding Protein 1; Carrier Proteins; Aged; Gene Expression Regulation, Leukemic; Telomeric Repeat Binding Protein 2; Sensitivity and Specificity; Adult; Down-Regulation; Piperazines; Middle Aged; Hematopoietic Stem Cells; Antigens, CD34; Transcription, Genetic; RNA; Humans; Disease Progression; Female; Tumor Suppressor Proteins; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male