hTERT expression and prognosis in B-chronic lymphocytic leukemia.
BACKGROUND
In B-chronic lymphocytic leukemia (B-CLL), there is a need for molecular markers to predict the evolution of this heterogeneous disease in individual patients. The level of expression of the human telomerase reverse transcriptase (hTERT) gene has been associated with disease aggressiveness in human cancers. The purpose of the present study was to examine the prognostic significance of hTERT expression in B-CLL.


METHODS
We used real-time reverse transcription-PCR to quantitate the amount of hTERT transcripts in mononuclear blood cells from 90 B-CLL patients. In addition, samples were analyzed for somatic mutations in the immunoglobulin V (IgV) genes.


RESULTS
The expression of hTERT gene was detected in 59% of patients. The level of expression increased with advancing B-CLL stage (P=0.0064). Patients expressing hTERT showed significantly shorter survival than hTERT-negative patients (P=0.000034), irrespective of the disease stage. On average, the level hTERT mRNA expression was seven-fold higher in the poor-prognosis B-CLL group with unmutated IgV than in the Ig-mutated group (P<10(-7)). The level of hTERT expression discriminated the Ig-unmutated from Ig-mutated B-CLL in 89% of cases.


CONCLUSIONS
Our data indicate that hTERT expression in B-CLL may serve as a molecular prognostic marker.
Tchirkov
A
A
Service d'Hématologie Clinique, CHU, Clermont-Ferrand. andrei.tchirkov@cjp.fr
Chaleteix
C
C
Magnac
C
C
Vasconcelos
Y
Y
Davi
F
F
Michel
A
A
Kwiatkowski
F
F
Tournilhac
O
O
Dighiero
G
G
Travade
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D020134:Catalytic Domain; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000032:analysis; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D019098:Telomerase / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D007135:Immunoglobulin Variable Region; D019098:Telomerase