Associações telomericas como indicadores de instabilidade cromossomica em pacientes com leucemias mieloides e sindromes mielodisplasicas

AUTOR(ES)
DATA DE PUBLICAÇÃO

1999

RESUMO

The associations between specific chromosomal abnormalities and different types of hematological neoplasias are well established. However, telomeric associations (tas), which are associations between termini regions of chromosomes (telomeres), are sporadicly observed in neoplasias, leading to the question about their role as a biological indicator of occupational exposure to environmental genotoxic agents. These associations can arise in consequence of shortening telomere length and the inhibition of telomerase activity, reflecting in chromosomal instabiblity The objective of this work was to determine the karyotype and to verify the occurrence of tas in MOS and acute or chronic myeloid leukemias (AML and CML). Metaphases of bone marrow cells of 30 patients (10 with MOS, 10 with AML and 10 with CML) were analyzed. The comparison of tas frequency data in these different hematological neoplasias was realized by the Kruskal Wallis test with significance levei of 5%. In the MOS patients, the clonal cytogenetic abnormalities findings were: monosomy of chromosome 7 in association with monosomy of chromosomes 13 and 20, trisomy of chromosomes 15, 19, 21, and tetrasomy of chromosome 22. New structural rearrangements were observed involving the 2q37, 4q35, 9p11, 12p13, 7p21 and 12q24 regions. Non-clonal chromosomal abnormalities were observed in AML,such as the trisomy of chromosome 14 and monosomy of chromosomes 1, 7 and 22, deletion of short arm of chromosome 7 and the presence of Philadelphia (Ph) chromosome. In CML, the results showed the presence of Ph chromosome as the principal clonal abnormality, as expected. An extra Ph chromosome and monosomy of chromosome Y, which are secondary chromosomal abnormalities, were also observed in some patients. Other non-clonal abnormalities such as poliploidy, hipodiploidy, hiperdiploidy, marker chromosome, chromatid break and precoce centromere division were occasionally observed. Wrth regard to tas, our results showed the presence this phenomenon in ali patients with MOS, AML and in eight among ten patients with CML. The frequency of metaphases with tas was higher in MOS; AML showed intermediate frequency and CML lower frequency. The comparison of these data showed significative difference between MOS and CML (pO.O5) and CML (p>O.O5) were detected. Considering our results, it s possible to suppose that agrochemicals can be inhibitors of telomerase activity, preferentially attaining the stem cells of bone marrow, leading to the loss of telomeric sequences and to the cytogenetic expression of tas. Thus, tas can be considered an indicator of chromosomal instability, related to environmental exposure to pesticides. However, our data are only indicative, because in the present study, there was a predominancy of individuais from rural zone, not allowing us to compare these data with occupational non-exposed individuais. Additional cytogenetics and molecular studies should be performed to investigate the relationship between telomerase activity and shortening telomere length with tas, in patients with hematological disease, exposed or non-exposed to environmental genotoxic agents such as pesticides

ASSUNTO(S)

hematologia leucemia cancer tumores

ACESSO AO ARTIGO

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