Telomere deregulations possess cytogenetic, phenotype, and prognostic specificities in acute leukemias.
OBJECTIVE
Telomeres are protected by tightly regulated factors and elongated by telomerase. Short and/or deprotected chromosomes are recombinogenic and thereby cancer prone.


METHODS
Together with the quantification of telomerase activity (TA), measuring telomere length (TL) and expression of the genes that govern telomere protection and elongation are useful for assessing telomere homeostasis.


RESULTS
By these means we demonstrate that TL, hTERT, and TA are in the order acute myelogenous leukemia (AML) > T-cell acute lymphoblastic leukemia (T-ALL) > B-cell acute lymphoblastic leukemia (B-ALL) > T-ALL > AML, and B-ALL > AML > T-ALL. AML0 and AML3 display the lowest amounts of hTERT transcripts, and ALL and AML cells with cytogenetic abnormalities possess the shortest telomeres. hTERT expression includes phenotype-specific RNA maturation and correlates with TA but not with TL. A wide ratio of TA to hTERT expression between leukemia subtypes suggests phenotype-specific hTERT post-transcriptional deregulations. B- and T-ALL overexpress Ku70 and Pinx1, T-ALL PTOP and RAP1, and B-ALL TRF2, the expression of which is significantly higher in cases with abnormal karyotype. hTERT transcription and TL correlate with response to intensive chemotherapy, and hTERT and RAD50 are independent prognostic factors for survival.


CONCLUSIONS
Each leukemia subtype possesses specific telomere dysregulations that rely on phenotype, karyotype, response to treatment, and survival.
Université Lyon I, Centre Léon Bérard, Oncovirologie et Biothérapies, FRE CNRS 3011, Lyon, France.
Valérie
V
Capraro
Linda
L
Zane
Delphine
D
Poncet
David
D
Perol
Perrine
P
Galia
Claude
C
Preudhomme
Nathalie
N
Bonnefoy-Berard
Eric
E
Gilson
Xavier
X
Thomas
Mohamed
M
El-Hamri
Youcef
Y
Chelghoun
Mauricette
M
Michallet
Eric
E
Wattel
Franck
F
Mortreux
David
D
Sibon
D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D011379:Prognosis; D016019:Survival Analysis; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C509186:TERT protein, human; D019098:Telomerase