RESUMO
In bone marrow cells of 33 patients with myelodysplastic syndrome and acute myeloid leukemia, structural rearrangements of chromosome 7 were found with conventional G-banding: 8 with deletions 7q and 25 with translocations. In 29 of the patients, complex karyotypes were confirmed using multicolor fluorescence in situ hybridization (mFISH). Commercial probes (Abbot Molecular) were used for 7q22, 7q31, and 7q35, the regions most frequently deleted in myeloid malignancies. In three cases without deletions, high-resolution multicolor banding (mBAND) for chromosome 7 revealed other aberrations. Five groups of chromosomal rearrangements were established: (a) deletion 7q as a sole aberration (2 cases), (b) deletion 7q and complex karyotypes (6 cases), (c) combined translocations and deletions of 7q (17 cases), (d) combined translocation and deletion 7p (5 cases), and (e) translocation of chromosomes 7 without deletion 7p or 7q (3 cases). Deletions of all three FISH-screened regions were the most frequent, with heterogeneous breakpoints. The region 7p13.2 approximately p15.2 was most commonly deleted. Most of the deletions were cryptic, not detectable with conventional cytogenetics. Aberrations of chromosome 7 are associated with a very poor outcome; survival time in our cohort was short (median 7 months).
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 7/genética , Leucemia Mieloide/patologia , Síndromes Mielodisplásicas/patologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Bandeamento Cromossômico , Deleção Cromossômica , Estudos de Coortes , Feminino , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Cariotipagem , Leucemia Mieloide/genética , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Prognóstico , Translocação GenéticaRESUMO
During progression of chronic myeloid leukemia (CML) from the chronic to the accelerated phase and/or blast crisis, clonal evolution with nonrandom secondary aberrations such as +8, +Ph, i(17q), +19, -Y, +21, +17, and -7 is frequently observed. Complex chromosomal rearrangements (CCR) are rather rare, and the significance and frequency of different anomalies are poorly understood. The aim of this study was to determine the chromosomes and chromosomal regions which are involved in CCR during progression of the disease and the frequency of nonrandom changes. Conventional cytogenetics, FISH, and multicolor FISH (mFISH) were used to study karyotypes of 18 CML patients with CCR ascertained by G-banding. Most often involved in CCR were chromosomes 2 (x6); 3, 7, and 17 (x5); 1 and 4 (x4); and 5, 6, 11, and 12 (x3); regions 1q, 2q, 5q, 7p, and 17p; and breakpoints 17p11.2 (x3) and 7p15 (x2). There were no recurrent complex translocations. The present findings demonstrate the very high instability of the genome of malignant cells at the chromosomal level. Precise determination of breakpoints involved in CCR can give new dimension to the understanding of genetic mechanisms which play role in progression of malignant disease.
