Telomere length in lymphoid malignancies: A comparative analysis

JULIETA PANERO; PATRICIA DOS SANTOS; IRMA SLAVUTSKY

Telomeres: Biological functions, sequencing and aging

Nova Science Publishers, Inc

Lugar: New York; Año: 2012; p. 53 - 77

Human telomeres are nucleoprotein complexes located at the end of chromosomes, composed of tandem repeats of the non-codificant DNA sequence TTAGGG. A core of six telomere binding proteins, the shelterin complex, serves to protect telomeric ends and to prevent recognition of chromosome ends as damaged DNA. Both critically short telomeres and direct disruption of the shelterin structure can initiate telomere dysfunction. The enzyme telomerase is a ribonucleoprotein that compensates the telomere reduction by adding new repeats to chromosome ends. Different studies have demonstrated that reduced telomere length (TL) contribute directly to genomic instability, usually found in several types of cancer. Short telomeres and high telomerase activity have been associated with tumorigenesis in patients with hematological neoplasm. Lymphoid malignancies constitute an heterogeneous group of lymphoproliferative disorders that represent distinct disease entities, according to their clinical, morphological, immunophenotypic and genetic features. In this study, we analyzed the TL in 262 patients with different B-cell malignancies and its association with genetic characteristics and telomere-associated proteins expression. TL was highly heterogeneous and significantly reduced in B-cell disorders compared to normal controls. Patients with diffuse large B-cell lymphoma secondary to follicular lymphoma (DLBCL-S) had the shortest telomeres, followed by follicular lymphoma (FL). Mantle cell lymphoma (MCL) and de novo DLBCL showed similar mean TL, whereas monoclonal gammopathy of undetermined significance (MGUS) and chronic lymphocytic leukemia (CLL) cases displayed the longest TL. Mean TL for multiple myeloma (MM) were intermediate among those entities. Significant shorter TL in MM and CLL patients with chromosomal abnormalities with respect to cases with normal karyotypes were observed (p