Assuntos
Proliferação de Células , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia-Linfoma de Células T do Adulto/complicações , Leucemia-Linfoma de Células T do Adulto/patologia , Células Precursoras de Linfócitos B/patologia , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antígenos CD/genética , Antígenos CD/imunologia , Cromossomos Humanos X/genética , Cromossomos Humanos X/imunologia , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Diarreia/tratamento farmacológico , Diarreia/etiologia , Diarreia/genética , Diarreia/imunologia , Evolução Fatal , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Sobrevivência de Enxerto/imunologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Íleus/tratamento farmacológico , Íleus/etiologia , Íleus/genética , Íleus/imunologia , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Infliximab , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/imunologia , Neoplasia Residual , Células Precursoras de Linfócitos B/imunologia , Quimeras de Transplante/genética , Quimeras de Transplante/imunologia , Condicionamento Pré-TransplanteRESUMO
The relative incidence of Hodgkin's disease (HD) has been found to have increased approximately seven times in HIV-infected patients. We analyzed the histological distribution of HIV-associated HD with the aim of clarifying purported difference(s) from de novo HD. References on HIV/AIDS-associated HD were retrieved from the most complete databases. Nineteen articles were the subject of our analysis. Seventeen of them reported data on the histological type of HIV/AIDS-associated HD patients; the route of infection and age of the patients were also considered when available. According to the Peto's methodology, histological types were compared with those from two large studies in the United States on de novo HD: 3,245 cases from the Surveillance, Epidemiology, and End Results (SEER) and 1,140 from Stanford University. The analysis of the two groups showed statistically significant differences (p<0.001) in the percentage of all histological types and odds ratios (OR) of the pooled effect of 0.4 (95% CI: 0.3-0.6) for lymphocyte predominance (LP), 0.3 (95% CI: 0.2-0.4) for nodular sclerosis (NS), 3.2 (95% CI: 2.6-3.8) for mixed cellularity (MC), and 6.3 (95% CI: 4.5-8.8) for lymphocyte depletion (LD). Comparison with the Stanford University series yielded similar results. Whilst retrospective and based on a limited number of cases, our data confirm a higher incidence of unfavorable histological subtypes in HIV-infected patients and show a reduction in the observed cases of good prognosis subtypes. Prospective studies, with careful histological observations, are required to better evaluate the characteristics of the LP subtype in the special setting of HIV infection.
Assuntos
HIV , Doença de Hodgkin/classificação , Doença de Hodgkin/virologia , Linfoma Relacionado a AIDS/epidemiologia , Doença de Hodgkin/epidemiologia , Humanos , Incidência , Linfoma Relacionado a AIDS/patologia , Prognóstico , Estudos RetrospectivosRESUMO
Recent reports have suggested a previously unexpected variability in the expression of the dominant neoplastic clone in myeloproliferative disorders (MPD). We evaluated 49 female patients with MPD and informative at the X-linked androgen receptor (AR) locus to establish the X chromosome inactivation pattern of hemopoietic cells. Whereas in chronic myelogenous leukemia (CML) the granulocytes (PMN) were uniformly of monoclonal origin, a striking heterogeneity of clonal development was found in PMN from patients with other MPD, with up to 50% of them expressing a polyclonal pattern of X inactivation.
Assuntos
Mecanismo Genético de Compensação de Dose , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologia , Receptores Androgênicos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Células Clonais/patologia , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Pessoa de Meia-Idade , Neutrófilos/patologia , Reação em Cadeia da Polimerase , Linfócitos T/patologiaRESUMO
The discovery of the C282Y and H63D point mutations in the hereditary hemochromatosis-associated HFE gene allows us to study the molecular basis of congenital and acquired iron overload disorders. In hereditary hemochromatosis an increased frequency of the C282Y and, to a lesser extent, of the H63D mutations has been established, but their role in other conditions associated with iron overload and their prevalence in the normal population are still under investigation. We sought to determine the presence of such mutations, and their possible involvement in the multi-step neoplastic transformation of the hepatocytes, in patients diagnosed with hepatocellular carcinoma, a frequent complication of iron-induced liver cirrhosis occurring in untreated hereditary hemochromatosis subjects. The frequency of the C282Y and H63D mutations was determined in DNA from 12 patients with hepatocellular carcinoma and with no clinical signs of hereditary hemochromatosis. The frequency of the mutations was also determined in 130 normal subjects. A germline C282Y mutation was found in none of the hepatocellular carcinoma patients; the frequency of the H63D mutation was not increased, compared to the 130 controls. The allele frequencies of the C282Y and H63D mutations in the normal population were 0.042 and 0.185, respectively. In conclusion, we suggest that the hereditary hemochromatosis-related mutations of the HFE gene do not play a significant role in the pathogenesis of hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Proteínas de Membrana , Idoso , Feminino , Frequência do Gene , Genes MHC Classe I , Antígenos HLA/sangue , Hemocromatose/sangue , Hemocromatose/complicações , Hemocromatose/genética , Proteína da Hemocromatose , Heterozigoto , Antígenos de Histocompatibilidade Classe I/sangue , Humanos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/genética , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/genética , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Fatores de RiscoAssuntos
Deficiência de Glucosefosfato Desidrogenase/complicações , Infecções por HIV/complicações , HIV-1 , Estresse Oxidativo , Progressão da Doença , Deficiência de Glucosefosfato Desidrogenase/mortalidade , Glutationa/metabolismo , Infecções por HIV/mortalidade , Humanos , Masculino , Análise de SobrevidaRESUMO
Since one of the two X chromosomes is randomly inactivated at an early stage of female embryonic development, X-linked markers have been used to study the origin and development of various neoplastic disorders in affected heterozygous women; clonality assays have provided a useful tool to the understanding of the mechanisms underlying the development of neoplasia. Recently, a technique of clonal analysis has been devised that takes advantage of a highly polymorphic short tandem repeat within the X-linked human androgen receptor (AR) gene, resulting in a heterozygosity rate approaching 90%. The rapid expansion of the number of women now suitable for X inactivation analysis has however given rise to new controversies, one of the more troublesome being the possibility of a modification of the pattern of X- chromosome inactivation pattern in blood cells of elderly women. In the present study we analyze with the AR assay a group of 166 healthy females aged between 8 and 94 years, with no history of genetic or neoplastic familial disorders. We failed to find any correlation between age and X- chromosome inactivation pattern (r = 0.17), even subdividing the subjects in different age groups according to the criteria used by other researchers, and therefore reaffirm that, when tested for with well-standardized and accurate criteria, extremely unbalanced inactivation of the X chromosome is a truly uncommon phenomenon in normal women.
Assuntos
Envelhecimento/genética , Mecanismo Genético de Compensação de Dose , Receptores Androgênicos/genética , Cromossomo X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Sanguíneas , Criança , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Familial Hodgkin's disease (FHD) is estimated to represent approximately 4.5% of all cases of Hodgkin's disease (HD). Shared environmental factors, such as Epstein-Barr virus and other viral agents, and genetic determinants have all been proposed to explain familial aggregation of HD. In order to compare the characteristic features of FHD with those of the much more common sporadic form, we reviewed 28 articles on FHD, published between 1972 and 1995, and analyzed in further detail data from 18 papers, reporting on a total of 328 patients. The male-to-female ratio of the FHD population examined was 1.5, similar to that reported for sporadic HD, and lower than the one suggested for FHD by some authors. On the other hand, a significant difference was found between sporadic and familial HD according to age at diagnosis; that is, only one major peak between 15 and 34 years was present in the group of patients with FHD. Further investigation of FHD in young adulthood may provide insight into the hypothesis of a genetic or infectious etiology of the disease.
Assuntos
Doença de Hodgkin/genética , Saúde da Família , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Estadiamento de Neoplasias , Razão de MasculinidadeRESUMO
Multiple endocrine neoplasia type 2 (MEN 2) is a dominantly inherited cancer syndrome characterized by medullary thyroid carcinoma (MTC) and other tumors. Since MTC can also occur in a sporadic form and as familial medullary thyroid carcinoma, this neoplasm offers a unique opportunity to investigate the difference of origin, if any, between the sporadic and the hereditary forms of a tumor. While sporadic malignancies have usually been found to result from a mutational event occurring at the single-cell level and are therefore monoclonal, studies on hereditary neoplasms have been scarce and often produced conflicting results. In order to determine the clonal origin of sporadic MTCs and of those occurring in MEN 2 syndromes we used a clonality assay based on a polymorphic trinucleotide repeat of the X-linked human androgen-receptor gene. We found that 10 out of 11 MTCs expressed a polyclonal pattern of X inactivation, including a significant percentage of the cases clinically defined as sporadic.
Assuntos
Carcinoma Medular/patologia , Neoplasia Endócrina Múltipla Tipo 2a/patologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Carcinoma Medular/genética , Células Clonais , Desoxirribonuclease HpaII , Desoxirribonucleases de Sítio Específico do Tipo II , Mecanismo Genético de Compensação de Dose , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/genética , Mutação Puntual , Reação em Cadeia da Polimerase , Receptores Androgênicos/genética , Neoplasias da Glândula Tireoide/genética , Repetições de TrinucleotídeosRESUMO
We report the unusual case of a 43-year-old man with a diagnosis of clinical stage I A mixed cellularity Hodgkin's disease (HD), who relapsed 4 years after diagnosis with exclusive bone marrow involvement and a cyclic variation in body temperature typical of Pel-Ebstein fever. In the absence of clinical and laboratory signs of infection, a restaging of the lymphoma was performed. Total-body CT scan revealed no parenchymal or lymph node involvement, while a bone-marrow biopsy was positive for the presence of Reed-Sternberg cells. Therefore, the patient was started on combination chemotherapy, which promptly induced a normalization of the temperature curve. The presence of typical Pel-Ebstein fever, which is reported to be very rare, in association with bone marrow localization as the only site of relapse, suggests a relationship between these two rare manifestations of the disease.
Assuntos
Febre , Doença de Hodgkin/fisiopatologia , Adulto , Medula Óssea/patologia , Doença de Hodgkin/patologia , Humanos , Masculino , PeriodicidadeRESUMO
Purified enzymes were mixed to form a cell-free system that simulated the conditions for removal of hydrogen peroxide within human erythrocytes. Human glutathione peroxidase disposed of hydrogen peroxide (H2O2) at a rate that was only 17% of the rate at which human catalase simultaneously removed hydrogen peroxide. The relative rates observed were in agreement with the relative rates predicted from the kinetic constants of the two enzymes. These results confirm two earlier studies on intact erythrocytes, which refuted the notion that glutathione peroxidase is the primary enzyme for removal of hydrogen peroxide within erythrocytes. The present findings differ from the results with intact cells, however, in showing that glutathione peroxidase accounts for even less than 50% of the removal of hydrogen peroxide. A means is proposed for calculating the relative contribution of glutathione peroxidase and catalase in other cells and species. The present results raise the possibility that the major function of glutathione peroxidase may be the disposal of organic peroxides rather than the removal of hydrogen peroxide.
Assuntos
Catalase/sangue , Eritrócitos/enzimologia , Peróxido de Hidrogênio/sangue , Sistema Livre de Células , Gluconatos/sangue , Glutationa/sangue , Glutationa Peroxidase/sangue , Humanos , NAD/sangueRESUMO
Following reports on a variety of interactions between glutathione (GSH) concentration and clinical parameters in solid tumors, a study was undertaken in order to determine the GSH intracellular content of chronic lymphocytic leukemia (CLL) lymphocytes. The results from a group of 16 patients consecutively studied indicate tht B-CLL cells have twice as much GSH as lymphocytes from normal subjects, suggesting that this measurement may be helpful in the understanding of the metabolic mechanism of the disease and the rationale of therapy.
Assuntos
Glutationa/sangue , Leucemia Linfocítica Crônica de Células B/sangue , Linfócitos/química , Glutationa/metabolismo , Humanos , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Linfócitos/patologiaRESUMO
The Ph chromosome abnormality is involved in the pathogenesis of almost all patients with chronic myelocytic leukemia (CML). Previous studies on the B-lymphoid cell lineage in two patients with Ph-positive CML suggest that there may also be a clonal Ph-negative stage in CML and that the Ph-positive stage arises by subclonal expansion. To determine whether this is a frequent or a rare occurrence, 14 additional glucose-6-phosphate dehydrogenase (G6PD)-heterozygous patients with CML were studied. In five of these patients there was a statistically significant excess of Ph-negative B-lymphoid cell lines expressing the same G6PD type expressed in the corresponding CML clone. In no case was an excess of B-lymphoid lines expressing the opposite G6PD type recovered. These data provide further evidence that in some patients the Ph chromosome arises in a pluripotent stem cell from a pre-existing Ph-negative clone that enjoys a growth advantage.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/enzimologia , Linfócitos B/patologia , Criança , Feminino , Ligação Genética , Glucosefosfato Desidrogenase/genética , Heterozigoto , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/enzimologia , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/patologia , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/enzimologia , Células-Tronco Neoplásicas/patologia , Cromossomo XRESUMO
It has been suggested that multiple myeloma, generally considered a neoplastic disorder of mature plasma cells, may arise from a pluripotent haemopoietic stem cell. The possibility that circulating lymphocytes derive from the same neoplastic progenitor has been tested in a large number of studies in the past few years, as proof of the interest that this subject is raising among scientists, and also of its elusiveness. We studied a group of 29 patients with plasma cell dyscrasias in order to evaluate clonality of haemopoietic cell populations. The X-linked markers hypoxantine phosphoribosyltransferase (HPRT) and phosphoglycerate kinase (PGK) disclosed no monoclonal component in seven heterozygous women. Analysis of immunoglobulin gene rearrangement with four probes showed a germline configuration in samples from 25/29 patients. Only four bone marrow samples from subjects with aggressive disease had rearranged C mu sequence; one had rearrangement of JH and C mu.
Assuntos
Paraproteinemias/genética , Paraproteinemias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Células Cultivadas , Feminino , Rearranjo Gênico , Células-Tronco Hematopoéticas/patologia , Heterozigoto , Humanos , Hipoxantina Fosforribosiltransferase/análise , Hipoxantina Fosforribosiltransferase/genética , Imunoglobulina G/genética , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Fosfoglicerato Quinase/análise , Fosfoglicerato Quinase/genéticaRESUMO
We studied N-ras and Ki-ras point mutations respectively at codons 12-13 and 12 in 15 patients with myelodysplastic syndromes (MDS) using the polymerase chain reaction (PCR) method for DNA amplification, and slot blot hybridization to allele specific oligonucleotide (ASO) probes. We analysed peripheral blood and bone marrow samples collected at diagnosis and repeatedly during the chronic phase of the disease to define when the activation occurred and in which haemopoietic cell populations, in order to establish possible relationships between clinical and molecular features. In three cases the N-ras oncogene was mutated at codon 12 in every cell population, both at diagnosis and throughout the chronic phase. Point mutations were not seen at the 12 codon of the Ki-ras oncogene. In patients lacking activated ras oncogene at diagnosis, mutations were not discovered during the entire period of observation. Therefore in our cases disease progression and leukaemic transformation did not correlate with the presence of the activated N-ras. Our data suggest that ras activation occurs early in the pathogenesis of MDS and involves a haemopoietic progenitor with multiple differentiative capacity, without however conferring an apparent proliferative advantage on its progeny.
Assuntos
Regulação da Expressão Gênica/fisiologia , Genes ras/fisiologia , Síndromes Mielodisplásicas/genética , Doença Crônica , DNA/genética , Humanos , Hibridização de Ácido Nucleico , Reação em Cadeia da PolimeraseRESUMO
Philadelphia (Ph) chromosome-positive chronic myelogenous leukaemia (CML) was studied in a subject heterozygous for the X chromosome-linked alloenzyme system of glucose-6-phosphate dehydrogenase (G6PD). Determination of G6PD mosaicism showed homogeneous expression in granulocytes, erythrocytes and platelets. Cytogenetic studies showed the typical Ph translocation in all metaphases from bone marrow and peripheral blood myeloid cells, bcr rearrangement was detected in bone marrow and in granulocytes. B cells were stimulated with Epstein-Barr virus (EBV) in order to evaluate involvement of lymphocytes, EBV-transformed lymphoblastoid cells expressed a single G6PD phenotype and therefore probably derived from the leukaemic stem cell. However they had a normal karyotype and a constitutional bcr restriction pattern. Molecular analysis in this case of CML clarifies the differentiative potential of cells belonging to the leukaemic clone, by demonstrating that clonal Ph-negative B cells maintain normal differentiative capacity and have a bcr gene sequence which is not rearranged.
Assuntos
Linfócitos B/fisiologia , Rearranjo Gênico do Linfócito B , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Cromossomo Filadélfia , Southern Blotting , Doença Crônica , Feminino , Glucosefosfato Desidrogenase/genética , Humanos , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/fisiologiaRESUMO
We describe here a patient with Ph'-positive chronic myelogenous leukemia (CML) who developed a Ph'-negative blastic crisis. The blast DNA was analyzed on two different occasions, at the beginning of the blastic phase and at the end, shortly before the patient's death. Although cells from both samples had no Ph' chromosome marker (not even a masked one) we could detect a rearrangement of the bcr gene in the second DNA sample, using a '3'-bcr' probe. The same probe and a '5'-bcr' probe failed to detect any rearranged band in the first DNA sample. No rearrangement was identified at the c-myc and N-ras loci, while a slight c-myc amplification was evident in both DNA samples tested.