RESUMO
Chromosome abnormalities detected in metaphases from multiple myeloma (MM) cells have a clear impact on prognosis and response to therapy. Thirteen out of 50 (26%) patients with plasma cell disorders and abnormal karyotypes (11 with MM and 2 with plasma cell leukemia (PCL)) were selected for inclusion in the present report based on the presence of karyotypes with new and/or infrequent structural aberrations. Thirty-three new rearrangements, including a novel recurrent aberration: psu dic(5;1)(q35;q10), were detected. Chromosome 1 was the most frequently involved. Gains of genetic material (57%) were noted more frequently than losses (43%). Three rearrangements that were observed only once in the literature appear to be recurrent from our data: del(16)(q13), del(5)(p13) and i(3)(q10), the latter being a single structural aberration in the karyotype. Clinical parameters from our series were compared with 2 control groups: 20 MM cases with recurrent aberrations in MM/PCL with a similar distribution of abnormalities associated with poor prognosis (group 1), and 40 with normal karyotypes and fluorescence in situ hybridization analysis (group 2). Significantly increased serum calcium levels (p = 0.022) in patients with new and/or infrequent chromosome changes with respect to both control groups, and a higher percentage of bone marrow plasma cell infiltration (p = 0.005), ß(2) microglobulin, and lactate dehydrogenase levels (p < 0.0001) compared to group 2 were observed. Our results suggest that some of these novel rearrangements may be capable to deregulate genetic mechanisms related to the development and/or progression of the disease. The finding of new recurrent aberrations supports this hypothesis.
Assuntos
Aberrações Cromossômicas , Leucemia Plasmocitária/genética , Mieloma Múltiplo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio/sangue , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 5/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Plasmocitária/sangue , Leucemia Plasmocitária/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/patologia , PrognósticoRESUMO
We have studied an extra structually abnormal chromosome (ESAC) in a 13 years old boy with profound mental, psychomotor and speech retardation, behavioral problems, seizures and abnormal electroencephalogram. The examination of the bisatellited ESAC with chromosome banding demonstrated that the karyotype was: 47, XY, +inv dup (15) (pter-->q13::q13-->pter). The cytogenetic characterization of the inv dup (15) is reported with special emphasis on the usefulness of DA/DAPI staining when G-banding is sequentially performed to discard possible heteromorphisms in DA/DAPI positive chromosomes, and the importance of Ag-NOR heteromorphisms to ascertain the maternal origin of the inv dup (15). A U-type exchange between two non-sister chromatids is proposed as its mechanism of formation. The clinical features of the case were consistent with those previously reported in similar cases.
Assuntos
Aberrações Cromossômicas , Inversão Cromossômica , Cromossomos Humanos Par 15 , Deficiência Intelectual/genética , Adolescente , Bandeamento Cromossômico , Mapeamento Cromossômico , Duplicação Gênica , Humanos , Deficiência Intelectual/patologia , Cariotipagem , Masculino , Transtornos Mentais/genética , Convulsões/genética , Distúrbios da Fala/genéticaRESUMO
AIMS: To present data obtained from human bone marrow preparations from healthy individual showing that the proportion of metaphases with silver stained nucleolar organiser region (AgNOR) chromosomes is associated with the age of the donor. METHODS: Bone marrow preparations from eight Russian and 10 Argentinian healthy individuals donating bone marrow for heterologous transplantation were studied by silver staining. The Russian bone marrow preparations were used directly, while the bone marrow specimens from Argentinian donors were incubated for 24 hours at 37 degrees C in F-10 medium with 15% fetal bovine serum. The slides were silver stained by the one step method of Howell and Black with slight modifications. Thirty metaphases with clearly defined D and G group chromosomes were scored for the numbers of AgNORs. All metaphases that were adjacent to silver stained interphase nuclei were analysed to assess the percentage of AgNOR positive mitoses. The Kruskal Wallis test and Kendall's rank correlation coefficient (rK) were used to assess the relation between age and the percentage of AgNOR positive cells. RESULTS: The mean numbers (SE) of AgNORs per metaphase were 5.06 (0.17) and 5.56 (0.23) for the Russian and Argentinian groups, respectively, with no significant differences between the two groups. The common percentage of AgNOR positive cells decreased significantly as a function of age, with an rK = -0.57 (p < 0.0012). CONCLUSIONS: The percentages of AgNOR negative metaphases in bone marrow from healthy individuals is strongly associated with age and this may be related to age related telomere loss.
Assuntos
Envelhecimento/genética , Cromossomos Humanos 13-15 , Cromossomos Humanos 21-22 e Y , Região Organizadora do Nucléolo/genética , Adolescente , Adulto , Células da Medula Óssea/ultraestrutura , Criança , Feminino , Humanos , Masculino , Metáfase/genética , Pessoa de Meia-Idade , Mitose/genética , Coloração pela PrataRESUMO
The simultaneous coexpression of lymphoid and myeloid markers has been observed in some cases of childhood acute lymphoblastic leukemias (ALL). In this paper, we describe a 6-year-old male patient with an ALL expressing myeloid antigens in whom a novel karyotypic association, t(8;22) and monosomy 7, and high Ag-NOR activity were found concomitantly with a very short survival.
Assuntos
Cromossomos Humanos Par 22 , Cromossomos Humanos Par 7 , Cromossomos Humanos Par 8 , Monossomia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Biomarcadores Tumorais , Criança , Humanos , MasculinoRESUMO
Silver staining of nucleolus organizing regions (Ag-NORs) of acrocentric chromosomes and the frequency of satellite association (SA) in bone marrow (BM) cells from 7 patients with mycosis fungoides (MF), were studied. BM samples of 7 normal healthy individuals were taken as controls. The mean number of Ag-NORs per metaphase was increased in patients (7.20 +/- 0.25) compared with controls (5.40 +/- 0.16) (p < 0.002), related with the increase of the D group. Moreover, a significant higher percentage of Ag-NOR positive cells in patients (71.7 +/- 3.9) than controls (48.0 +/- 7.8) (p < 0.02), was seen. The analysis of SA revealed a significant increase in the percentage of cells with 1-2 association pairs (ASPs) in patients with respect to their controls (p < 0.05), and a trend to a decrease in the percentage of cells without ASPs. Furthermore, a correlation between the number of Ag-NORs and the mean of ASPs per cell was also found for patients (rk = 0.65; p < 0.05). These results may be associated with a certain degree of immaturity, a high proliferative activity and modifications of the growth rate of BM cells in MF patients.
Assuntos
Medula Óssea/patologia , Micose Fungoide/patologia , Região Organizadora do Nucléolo/patologia , Adolescente , Adulto , Idoso , Células da Medula Óssea , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Micose Fungoide/genética , Valores de Referência , Prata , Coloração e Rotulagem/métodosRESUMO
The nucleolar organizer regions (NORs) activity and the frequency of satellite associations (SA) in peripheral blood lymphocytes from patients with two chronic lymphoproliferative disorders were studied: 10 cases with B-cell chronic lymphocytic leukemia (B-CLL) and 10 with mycosis fungoides (MF). Thirteen healthy individuals formed the MF control group, and the oldest 7 constituted the B-CLL control group. The mean of Ag-NORs per metaphase was increased in B-CLL patients (8.80 +/- 0.63) compared with their controls (7.99 +/- 0.90) (P less than 0.025), meanwhile MF patients' value did not differ from their controls. In both disorders, the frequency of Ag-NORs in the G chromosomes was increased. The analysis of SA in B-CLL patients only revealed an increase in the frequency of cells with more than 4 ASPs (association pairs). Meanwhile, a significant higher mean of ASPs per cell in MF patients (1.74 +/- 0.41) compared to controls (1.40 +/- 0.24) (P less than 0.05) was observed. Furthermore, a close correlation between cells with complexes of 3 or more chromosomes and the mean of ASPs per cell was also found in MF. In conclusion, an increase of the Ag-NORs expression in B-CLL patients and a modification in the degree of SA in MF patients were found.