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1.
Tumour Biol ; 36(2): 711-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25286758

RESUMO

Recent technological advances have made it possible to detect circulating tumor cells (CTCs) as a prognostic marker in operable breast cancer patients. Whether the presence of CTCs in cancer patients correlates with molecular alterations in the primary tumor has not been widely explored. We identified 14 primary breast cancer specimens with known CTC status, in order to evaluate the presence of differential genetic aberrations by using SNP array assay. There was a global increase of altered genome, CNA, and copy-neutral loss of heterozygosity (cn-LOH) observed in the CTC-positive (CTC(+)) versus CTC-negative (CTC(-)) cases. As the preliminary results showed a higher proportion of copy number alteration (CNA) at 8q24 (MYC loci) and the available evidence supporting the role of MYC in the processes cancer metastases is conflicting, MYC status was determined in tissue microarray sections in a larger series of patients (n = 49) with known CTC status using FISH. MYC was altered in 62% (16/26) CTC(+) patients and in 43% (6/14) CTC(-) patients (p = 0.25). Based on the observation in our study, future studies involving a larger number of patients should be performed in order to definitively define if this correlation exists.


Assuntos
Neoplasias da Mama/genética , Variações do Número de Cópias de DNA/genética , Genes myc/genética , Perda de Heterozigosidade/genética , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Células Neoplásicas Circulantes , Polimorfismo de Nucleotídeo Único/genética
2.
Kidney Int ; 80(8): 822-831, 2011 10.
Artigo em Inglês | MEDLINE | ID: mdl-21814178

RESUMO

Ischemic renal injury is a formidable clinical problem, the pathophysiology of which is incompletely understood. As the Na/H exchanger-3 (NHE3) mediates the bulk of apical sodium transport and a significant fraction of oxygen consumption in the proximal tubule, we examined mechanisms by which ischemia-reperfusion affects the expression of NHE3. Ischemia-reperfusion dramatically decreased NHE3 protein and mRNA (immunohistochemistry, immunoblot, and RNA blot) in rat kidney cortex and medulla. The decrease in NHE3 protein was uniform throughout all tubules, including those appearing morphologically intact. In the kidney cortex, a decrease in NHE3 surface protein preceded that of NHE3 total protein and mRNA. Kidney homogenates from rats exposed to mild renal ischemia-reduced cell surface NHE3 protein expression in opossum kidney cells in vitro, whereas homogenates from animals with moderate-to-severe ischemia reduced both total NHE3 protein and mRNA. The decrease in total NHE3 protein was dependent on the proteasomal degradation associated with NHE3 ubiquitylation measured by coimmunoprecipitation. The transferable factor(s) from the ischemic homogenate that reduce NHE3 expression were found to be heat sensitive and to be associated with a lipid-enriched fraction, and did not include regulatory RNAs. Thus, transferable factor(s) mediate the ischemia-reperfusion injury-induced decrease in NHE3 of the kidney.


Assuntos
Traumatismo por Reperfusão/metabolismo , Trocadores de Sódio-Hidrogênio/fisiologia , Tromboplastina/fisiologia , Doença Aguda , Animais , Células Cultivadas , Imuno-Histoquímica , Gambás , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Trocador 3 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/análise , Trocadores de Sódio-Hidrogênio/genética
3.
Sci Rep ; 11(1): 6315, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737699

RESUMO

There is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was firstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90× vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of differences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE.


Assuntos
Galinhas/microbiologia , Infecções por Clostridium/microbiologia , Enterite/microbiologia , Doenças das Aves Domésticas/microbiologia , Ração Animal/microbiologia , Animais , Infecções por Clostridium/genética , Clostridium perfringens/efeitos dos fármacos , Clostridium perfringens/patogenicidade , Coccidiose/genética , Coccidiose/microbiologia , Coccidiose/prevenção & controle , Suplementos Nutricionais , Eimeria/efeitos dos fármacos , Eimeria/patogenicidade , Enterite/genética , Enterite/prevenção & controle , Expressão Gênica/efeitos dos fármacos , Humanos , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/prevenção & controle , Vacinas/farmacologia
4.
Leukemia ; 35(3): 835-849, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32595214

RESUMO

In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.


Assuntos
Biomarcadores Tumorais/análise , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/diagnóstico , Segunda Neoplasia Primária/classificação , Segunda Neoplasia Primária/diagnóstico , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Segunda Neoplasia Primária/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
5.
Br J Dermatol ; 163(5): 1028-35, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20662834

RESUMO

BACKGROUND: Oncogenesis in the oral cavity is believed to result from genetic alterations that cause a stepwise transformation of the mucosa to invasive carcinoma. In oral squamous cell carcinoma (OSCC) multiple cytogenetic abnormalities have been reported, but their practical significance remains uncertain. OBJECTIVE: To evaluate the usefulness of the assessment of CCND1, MYC, EGFR, ERBB2 and TP53 in OSCC and lymph node metastases. METHODS: Fifty-one consecutive samples of OSCC, nine lymph node biopsies showing metastatic spread from OSCC, 16 biopsies diagnosed as oral leucoplakia (OLK), 13 samples corresponding to oral lichen planus (OLP) and 14 samples from normal oral mucosa were included in the study. Clinical and histopathological characteristics were reviewed. The genetic and protein status of the CCND1, MYC, EGFR, ERBB2 oncogenes and the TP53 tumour suppressor gene were assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The obtained results were compared with the clinical characteristics and the outcome of the OSCCs. RESULTS: TP53 gene losses and MYC, ERBB2, CCND1 and EGFR copy number gains and amplifications were detected in a higher proportion in OSCC and lymph node samples than in OLK and OLP samples (P < 0·005). Overexpression of p53, Myc, Cyclin D1, c-erbB-2 and epidermal growth factor receptor (EGFR) was more prevalent in malignant samples than benign samples (P < 0·05). Correlation between FISH and IHC results was demonstrated in MYC, EGFR and CCND1 studies. The presence of two or more genetic abnormalities in the studied loci was exclusively detected in primary and metastatic OSCC. CONCLUSIONS: In our series, genetic abnormalities in TP53, MYC, CCND1, ERBB2 and EGFR detected by FISH were absent in inflammatory lesions, infrequent in precursor lesions and common in tumoral lesions. Evaluation of the genetic status of TP53, MYC, CCND1, ERBB2 and EGFR may be an additional diagnostic tool in distinguishing benign from malignant oral lesions in histopathologically challenging cases.


Assuntos
Carcinoma de Células Escamosas/genética , Dosagem de Genes , Neoplasias Bucais/genética , Oncogenes/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biópsia , Ciclina D1/genética , Ciclina D1/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Genes p53/genética , Humanos , Linfonodos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo
6.
Br J Dermatol ; 161(5): 1112-8, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19673870

RESUMO

BACKGROUND: The genetic alterations that drive the transition from actinic keratoses (AKs) to cutaneous squamous cell carcinomas (SCCs) have not been defined precisely. Amplification and/or overexpression of the MYC proto-oncogene have been demonstrated in several human, malignant tumours including head and neck SCCs. OBJECTIVES: To evaluate the presence of MYC genomic aberrations in both AKs and SCCs. METHODS: Skin biopsy specimens corresponding to AKs, SCCs and control samples were included in two paraffin-embedded tissue microarrays. MYC cytogenetic profile was evaluated by fluorescence in situ hybridization (FISH). The results obtained were compared with MYC immunohistochemical expression. RESULTS: Twenty-three AKs and 30 SCCs were evaluated. MYC numerical aberrations were observed in eight of 23 (35%) AKs and 19 of 30 (63%) SCCs (P = 0.05). MYC numerical aberrations were more frequent in moderately to poorly differentiated SCCs (77%) when compared with well-differentiated SCCs (25%; P = 0.027). A significant association between copy number gains of MYC by FISH analysis and MYC protein expression was demonstrated. CONCLUSIONS: MYC gains and amplifications are frequent cytogenetic abnormalities in SCCs and may play a relevant role in promoting SCC undifferentiation and tumoral progression.


Assuntos
Carcinoma de Células Escamosas/genética , Aberrações Cromossômicas , Progressão da Doença , Genes myc/genética , Ceratose Actínica/genética , Neoplasias Cutâneas/genética , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Ceratose Actínica/patologia , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Proto-Oncogene Mas , Neoplasias Cutâneas/patologia
7.
Leukemia ; 21(7): 1532-44, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17495977

RESUMO

The biologic and pathologic features of B-cell malignancies bearing a translocation t(14;19)(q32;q13) leading to a fusion of IGH and BCL3 are still poorly described. Herein we report the results of a comprehensive cytogenetic, fluorescence in situ hybridization (FISH), molecular and histopathological survey of a large series of B-cell malignancies with t(14;19) or variant translocations. A total of 56 B-cell malignancies with a FISH-proven BCL3 involvement were identified with the translocation partners being IGH (n=51), IGL (n=2), IGK (n=2) and a non-IG locus (n=1). Hierarchical clustering of chromosomal changes associated with the t(14;19) indicated the presence of two different groups of IG/BCL3-positive lymphatic neoplasias. The first group included 26 B-cell malignancies of various histologic subtypes containing a relatively high number of chromosomal changes and mostly mutated IgVH genes. This cluster displayed three cytogenetic branches, one with rearrangements in 7q, another with deletions in 17p and a third one with rearrangements in 1q and deletions in 6q and 13q. The second group included 19 cases, mostly diagnosed as B-cell chronic lymphocytic leukemia (B-CLL), and characterized by few additional chromosomal changes (e.g. trisomy 12) and unmutated IgVH genes. In conclusion, our study indicates that BCL3 translocations are not restricted to B-CLL but present in a heterogeneous group of B-cell malignancies.


Assuntos
Leucemia de Células B/genética , Linfoma de Células B/genética , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/genética , Translocação Genética , Adulto , Idoso , Proteína 3 do Linfoma de Células B , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 19 , Análise Citogenética , Feminino , Rearranjo Gênico , Genes de Imunoglobulinas , Histocitoquímica , Humanos , Hibridização in Situ Fluorescente , Leucemia de Células B/classificação , Leucemia de Células B/patologia , Linfoma de Células B/classificação , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade
8.
J Hematol Oncol ; 11(1): 96, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-30041662

RESUMO

Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.


Assuntos
Inibidor de Quinase Dependente de Ciclina p15/genética , Deleção de Genes , Genes p16 , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Proteína Supressora de Tumor p14ARF/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Prognóstico
9.
Cytogenet Genome Res ; 118(1): 84-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17901705

RESUMO

We report on a novel case of pure partial tandem duplication 1q42q43 confirmed by fluorescence in situ hybridization (FISH). We compare the manifestations of our patient with similar cases previously reported. We conclude that the most common clinical manifestations of trisomy 1q42qter are prenatal and postnatal growth retardation, relative macrocephaly, triangular face, prominent forehead, broad nasal bridge, abnormal philtrum, micro/retrognathia, cardiac defects and mental retardation. We would like to emphasize the importance of the FISH technique in the identification of the duplicated segment.


Assuntos
Cromossomos Humanos Par 1 , Trissomia , Pré-Escolar , Fácies , Feminino , Humanos , Hibridização in Situ Fluorescente , Deficiência Intelectual/genética , Masculino
10.
Clin Neuropathol ; 26(1): 12-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17290931

RESUMO

Primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS), a rare occurrence in adults, may show glial differentiation and can be misinterpreted as pure astrocytic neoplasms. Few fluorescence in situ hybridization (FISH) studies have been carried out on these tumors; isochromosome 17q was found to be the major chromosomal abnormality. We present the case of an adult in which we performed a FISH study of both the glial and neuronal components. A complex array of FISH changes, not including an isochromosome 17q were identified.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Cromossomos Humanos Par 17/genética , Tumores Neuroectodérmicos Primitivos/genética , Tumores Neuroectodérmicos Primitivos/patologia , Trissomia/genética , Adulto , Humanos , Hibridização in Situ Fluorescente , Masculino
12.
Leukemia ; 9(2): 271-3, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7869763

RESUMO

The in vitro cultures of haematopoietic progenitors have been reported to be useful in the diagnosis of myeloproliferative disorders since the so-called endogenous erythroid and megakaryocyte colony formation has, in most studies, been found in these diseases. In order to know their value as diagnostic criteria in essential thrombocythaemia (ET) we have studied megakaryocyte (with and without phytohaemagglutinin-stimulated leucocyte conditioned medium) and erythroid (with and without erythropoietin) colony formation in vitro by progenitors from blood in 60 patients with ET and in ten with reactive thrombocytosis (RT) using the methyl-cellulose assay. Out of 60 ET patients endogenous megakaryocyte colony growth was observed in 38 (63%) and endogenous erythroid growth in 42 (70%). None of the patients with RT or any of the controls showed either type of endogenous growth. Fifty-five (91%) of the patients with ET showed megakaryocyte and/or erythroid endogenous colony formation whereas five (9%) did not have any kind of endogenous colonies, although cultures were performed sequentially. In conclusion, a positive endogenous megakaryocyte and/or erythroid colony growth from blood is a frequent and characteristic finding in ET patients and should be used as a useful marker in this disease.


Assuntos
Células Precursoras Eritroides/patologia , Megacariócitos/patologia , Trombocitemia Essencial/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Trombocitemia Essencial/patologia , Trombocitose/sangue , Trombocitose/patologia
13.
Leukemia ; 13(2): 150-4, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10025886

RESUMO

To determine the clinicohematological factors predictive for the appearance of major vascular complications (MVC) in patients with essential thrombocythemia (ET), 148 consecutive such patients were retrospectively assessed for the development of MVC during a median follow-up of 58.5 months. Seventy-seven patients had vascular risk factors, and 37 a history of MVC at ET diagnosis. Forty-nine MVC were registered in 33 patients during the follow-up period. The actuarial probability of MVC was 27% at 6 years in the whole series, 35.6% for patients above 60 years, and 21.4% for patients younger than 60 years, whereas only one of the 36 patients younger than 45 years had MVC. At multivariate analysis, age >60 years, history of major ischemia and hypercholesterolemia were the variables associated with an increased MVC risk. These results suggest that all ET patients above 60 years should be treated, whereas in younger patients treatment decisions should be primarily based on the existence of risk factors for MVC.


Assuntos
Trombocitemia Essencial/complicações , Doenças Vasculares/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Doenças Vasculares/etiologia
14.
Leukemia ; 15(9): 1475-84, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11516111

RESUMO

Structural alterations in 3q27 affecting the BCL6 locus are among the most frequent changes in B-NHL. The aim of the present study was to establish an interphase-FISH assay for the detection of all diverse BCL6 translocations in B-NHL. Two different approaches were tested, one using a PAC-clone spanning the major breakpoint region (MBR) of BCL6 (span-assay), and another using two BAC clones flanking the MBR (flank-assay). Interphase FISH with the span-assay detected the various BCL6 translocations in seven B-NHL cell lines. The dual-color flank-assay was evaluated in two laboratories independently: in normal controls, the cutoff level for false-positive signals was 2.6%, whereas the cutoff level for false-negatives in the seven cell lines was 7.5%. To test the feasibility of the FISH strategies, 30 samples from patients with B-NHL with cytogenetic abnormalities of 3q27 were evaluated with both assays. In 21 cases, the span-assay indicated a BCL6 rearrangement. In 18 of the 21 cases, the dual-color flank-assay confirmed the translocation including 12 different partner chromosomal loci. The three false-positive cases detected with the span-assay showed trisomy of chromosome 3 by cytogenetic analyses, and they were correctly classified as non-rearranged with the flank-assay. In summary, our FISH strategy using two differently labeled flanking BCL6 BAC probes provides a robust, sensitive, and reproducible method for the detection of common and uncommon abnormalities of BCL6 gene in interphase nuclei. The routine application of this assay to patients with B-NHL will allow the assessment of the diagnostic and prognostic significance of BCL6 rearrangements.


Assuntos
Cromossomos Humanos Par 3 , Linfoma de Células B/genética , Translocação Genética , Sequência de Bases , Bandeamento Cromossômico , Feminino , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Dados de Sequência Molecular
15.
Blood Cancer J ; 5: e291, 2015 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-25768405

RESUMO

Nonsynonymous TP53 exon 4 single-nucleotide polymorphism (SNP), R72P, is linked to cancer and mutagen susceptibility. R72P associations with specific cancer risk, particularly hematological malignancies, have been conflicting. Myelodysplastic syndrome (MDS) with chromosome 5q deletion is characterized by erythroid hypoplasia arising from lineage-specific p53 accumulation resulting from ribosomal insufficiency. We hypothesized that apoptotically diminished R72P C-allele may influence predisposition to del(5q) MDS. Bone marrow and blood DNA was sequenced from 705 MDS cases (333 del(5q), 372 non-del(5q)) and 157 controls. Genotype distribution did not significantly differ between del(5q) cases (12.6% CC, 38.1% CG, 49.2% GG), non-del(5q) cases (9.7% CC, 44.6% CG, 45.7% GG) and controls (7.6% CC, 37.6% CG, 54.8% GG) (P=0.13). Allele frequency did not differ between non-del(5q) and del(5q) cases (P=0.91) but trended towards increased C-allele frequency comparing non-del(5q) (P=0.08) and del(5q) (P=0.10) cases with controls. Median lenalidomide response duration increased proportionate to C-allele dosage in del(5q) patients (2.2 (CC), 1.3 (CG) and 0.89 years (GG)). Furthermore, C-allele homozygosity in del(5q) was associated with prolonged overall and progression-free survival and non-terminal interstitial deletions that excluded 5q34, whereas G-allele homozygozity was associated with inferior outcome and terminal deletions involving 5q34 (P=0.05). These findings comprise the largest MDS R72P SNP analysis.


Assuntos
Deleção Cromossômica , Síndromes Mielodisplásicas/genética , Proteína Supressora de Tumor p53/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Frequência do Gene , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento
16.
Leukemia ; 29(7): 1502-13, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25721895

RESUMO

A risk-adapted treatment strategy is mandatory for myelodysplastic syndromes (MDS). We refined the World Health Organization (WHO)-classification-based Prognostic Scoring System (WPSS) by determining the impact of the newer clinical and cytogenetic features, and we compared its prognostic power to that of the revised International Prognostic Scoring System (IPSS-R). A population of 5326 untreated MDS was considered. We analyzed single WPSS parameters and confirmed that the WHO classification and severe anemia provide important prognostic information in MDS. A strong correlation was found between the WPSS including the new cytogenetic risk stratification and WPSS adopting original criteria. We then compared WPSS with the IPSS-R prognostic system. A highly significant correlation was found between the WPSS and IPSS-R risk classifications. Discrepancies did occur among lower-risk patients in whom the number of dysplastic hematopoietic lineages as assessed by morphology did not reflect the severity of peripheral blood cytopenias and/or increased marrow blast count. Moreover, severe anemia has higher prognostic weight in the WPSS versus IPSS-R model. Overall, both systems well represent the prognostic risk of MDS patients defined by WHO morphologic criteria. This study provides relevant in formation for the implementation of risk-adapted strategies in MDS.


Assuntos
Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/diagnóstico , Organização Mundial da Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Análise Citogenética , Feminino , Seguimentos , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Estadiamento de Neoplasias , Prognóstico , Projetos de Pesquisa , Medição de Risco , Taxa de Sobrevida , Adulto Jovem
17.
Am J Surg Pathol ; 25(10): 1268-76, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11688461

RESUMO

Splenic marginal zone lymphoma (SMZL) is considered to be an indolent extranodal B-cell lymphoma. Despite its low aggressivity, histologic progression has been described in sporadic reports, although the frequency, characteristics, and underlying molecular abnormalities of this phenomenon are largely unknown. We review here the clinical, morphologic, immunohistochemical, and molecular features of a series of 12 SMZL cases that showed progression to large B-cell lymphoma (LBCL). The most frequent location of secondary LBCL was in peripheral lymph node. This occurred between 12 and 85 months after diagnosis of SMZL. However, in two cases LBCL was diagnosed at the initial stage of the disease (one spleen tumoral nodule and one hilar lymph node). The histologic and immunophenotypic features of these cases were similar to those of transformed LBCL at other sites. In four cases the immunoglobulin heavy chain gene polymerase chain study revealed the same rearrangement pattern in both primary and secondary tumors, thereby confirming their identity and excluding the possibility of a second malignancy. As is the case with other low-grade lymphoproliferative disorders, SMZL may undergo high-grade transformation. These 12 cases represent 13% of our series of SMZL with adequate follow-up. The incidence of large cell transformation in SMZL seems to be lower than in follicular lymphoma (25-60%) and mantle cell lymphoma (11-39%), although it is similar to the frequency of transformation in B-chronic lymphocytic lymphoma/small lymphocytic lymphoma (1-10%). The mean proliferative index (MIB1 staining) in initial SMZL specimens of cases with LBCL transformation was 28.6%, higher than that of MIB1 staining in the overall SMZL series (21.8%), although not statistically significantly so. p53 or p16INK4a inactivation in this series was observed in only one case, in contrast with the situation observed in chronic lymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma. It seems that progression in SMZL is mainly independent of p53 or p16INK4a inactivation. The frequency of the 7q deletion in this series was 3 of 7 (42%). 7q loss may play an alternative role in the inactivation of the p53 and p16INK4a pathway, thereby favoring tumoral progression.


Assuntos
Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Neoplasias Esplênicas/patologia , Adulto , Idoso , Alelos , Antígenos Nucleares , Biomarcadores Tumorais/análise , Deleção Cromossômica , Cromossomos Humanos Par 7 , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/genética , Análise Mutacional de DNA , DNA de Neoplasias/análise , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/genética , Progressão da Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Imunofenotipagem , Linfoma de Células B/química , Linfoma de Células B/genética , Linfoma de Células B/mortalidade , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/análise , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-6 , Neoplasias Esplênicas/química , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/mortalidade , Taxa de Sobrevida , Fatores de Transcrição/análise , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/genética
18.
Leuk Res ; 20(5): 369-74, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8683974

RESUMO

We have studied 61 cases of B-chronic lymphocytic leukemia (CLL), combining cytological features, conventional cytogenetics and in situ hybridization (ISH). The comparison of these results constitutes the main subject of this study. The patients were cytologically classified according to the FAB criteria as: chronic lymphocytic leukemia (CLL) typical type (48 cases) and CLL atypical types (13 cases). Chromosome analysis was carried out on lymphoid cells from peripheral blood. The following mitogens were used: phytohemagglutinin (PHA) 5%, pokeweed (PWM) and lipopolysaccharide from E. coli. The ISH was performed with a biotin-labeled, chromosome 12-specific alpha satellite DNA probe, pSP12-1. Trisomy 12 was not found in any of the 48 patients with the typical type of CLL and in contradistinction it was present in some patients with atypical types. This study emphasizes the great importance of a closer link between hematological morphology and the cytogenetic approach.


Assuntos
Cromossomos Humanos Par 12 , Leucemia Linfocítica Crônica de Células B/genética , Trissomia , Idoso , Idoso de 80 Anos ou mais , Estudos de Avaliação como Assunto , Feminino , Humanos , Hibridização In Situ , Cariotipagem , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
19.
Leuk Res ; 18(9): 671-3, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7934142

RESUMO

We report a case of multiple myeloma with a t(8;22)(q24;q11) found during the progression of the disease. The relation between the association of a Burkitt's type translocation with cytological characteristic features is presented. To our knowledge, there is no report of a multiple myeloma with t(8;22)(q24;11).


Assuntos
Linfoma de Burkitt/genética , Mieloma Múltiplo/genética , Translocação Genética , Idoso , Medula Óssea/patologia , Mapeamento Cromossômico , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 22 , Cromossomos Humanos Par 5 , Cromossomos Humanos Par 8 , Humanos , Cariotipagem , Masculino , Mieloma Múltiplo/patologia , Trissomia
20.
Leuk Res ; 17(8): 717-20, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8355516

RESUMO

We report four patients with myelodysplastic syndrome (MDS) with isochromosome i(17q) as the sole chromosomal anomaly. One patient was classified as refractory anemia (RA) and three as refractory anemia with excess of blasts (RAEB). All four patients shared several features such as male sex, advanced age, severe anemia, as well as a bone marrow with myeloproliferative characteristics: hypercellularity, prominent baso- and eosinophilia, and marked increase of micromegakaryocytes. We suggest that patients with i(17q) as the sole chromosomal anomaly may identify a distinct MDS with characteristics between MDS and chronic myeloproliferative disorders (CMPD).


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 17 , Síndromes Mielodisplásicas/genética , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/etiologia , Eritropoese , Humanos , Cariotipagem , Contagem de Leucócitos , Masculino , Síndromes Mielodisplásicas/sangue
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