RESUMO
Biphenotypic acute leukemias (BAL) represent 5% of all acute leukemias. The most frequent cytogenetic abnormalities described are Philadelphia chromosome and 11q23 involvement. Here we report a BAL case, with blasts showing lymphoblast morphology and positivity for myeloperoxidase (in 6% of the blast cells). Immunophenotype revealed the compromise of myeloid and B-lymphoid lineages. Cytogenetic analysis showed the t(15;17) and 8 trisomy. PML/RARa rearrangement was detected by fluorescent in situ hybridization (FISH) on interphase nuclei while PML/RARa fusion transcript was detected in the bone marrow and peripheral blood by molecular biology studies (RT-PCR). This report describes a BAL case with an unfrequent cytogenetic abnormality, and highlights the importance of correlating the results of multiple diagnostic methods in order to establish a correct diagnosis and treatment in BAL patients.
Assuntos
Inversão Cromossômica , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 17/genética , Leucemia/genética , Doença Aguda , Criança , Aberrações Cromossômicas , Cromossomos Humanos Par 8/genética , Feminino , Citometria de Fluxo/métodos , Rearranjo Gênico , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente/métodos , Leucemia/patologia , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , TrissomiaAssuntos
Proteínas de Fusão bcr-abl/biossíntese , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Trombocitose/complicações , Adolescente , Adulto , Idoso , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição GênicaRESUMO
Vinca alkaloids are used clinically against a variety of hematological and solid tumors. These compounds interact with tubulin subunits to prevent microtubule assembly, inducing abnormal chromosome segregation in dividing cells and causing aneuploidy. The vinca alkaloid vincristine sulfate (VCR) and the semisynthetic analog vinorelbine (VRB) were studied by analysis of micronuclei (MN) in cultured human lymphocytes using the cytokinesis block method. Furthermore, fluorescence in situ hybridization with a human alphoid satellite pancentromeric DNA probe was used to detect centromeres in isolated MN of VRB- or VCR-treated lymphocytes. At all the doses tested, both chemicals induced a significant increase in MN frequencies in binucleated (BN) cells (P < 0.001). The maximal effect was reached at a dose of 0.50 microgram/ml. At this dose, VRB produced an approximately 5-fold increase with respect to the control frequency of MN, while with VCR, this frequency increased 10-fold. Both drugs produced a slowing of the cell cycle, causing a decrease in the percentage of BN cells. This effect was lower with VRB. The percentages of centromere-positive MN were 89.79 and 87.60% in VRB- and VCR-treated cultures, respectively (control 27.03%). The high percentage of positive-signals in treated cultures (P < 0.001) indicates that the MN contained whole chromosomes. Our results confirm the aneugenic mode of action of these chemicals, VRB having less genetic effect.
Assuntos
Linfócitos/efeitos dos fármacos , Fuso Acromático/efeitos dos fármacos , Vimblastina/análogos & derivados , Vincristina/toxicidade , Adulto , Antineoplásicos Fitogênicos/toxicidade , Células Cultivadas , Centrômero/efeitos dos fármacos , Feminino , Inibidores do Crescimento/toxicidade , Humanos , Linfócitos/citologia , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Vimblastina/toxicidade , VinorelbinaRESUMO
Aneugenic effects of the Vinca alkaloid vinorelbine (VRB) were evaluated in vitro, measuring sister chromatid exchanges (SCE), cell proliferation kinetics and anaphase telophase aberrations in Chinese hamster ovary (CHO) cells. The highest dose of VRB (0.50 microg/ml) arrested cells at the first metaphase. An increase in abnormal anaphases was seen at 0.05-0.50 microg/ml of VRB, containing chiefly lagging chromosomes and multipolar spindles. No increase in SCE was found. These results indicate that VRB does not directly damage DNA, but acts on spindle microtubules, altering chromosome movement and causing aneuploidy.