RESUMO
We previously showed that complex karyotypes (CK) and chromosome 13q abnormalities have an adverse prognostic impact in childhood Burkitt lymphomas/leukemias (BL) and diffuse large B-cell lymphomas (DLBCL). The aim of our study was to identify recurrent alterations associated with MYC rearrangements in aggressive B-cell lymphomas with CK. Multicolor fluorescence in situ hybridization (M-FISH) was performed in 84 patient samples (59 adults and 25 children), including 37 BL (13 lymphomas and 24 acute leukemias), 12 DLBCL, 28 B-cell lymphomas with intermediate features (DLBCL/BL), 4 B-cell precursor acute lymphoblastic leukemias (BCP-ALL), and 3 unclassifiable B-cell lymphomas. New (cytogenetically undetected) abnormalities were identified in 80% of patients. We also refined one-third of the chromosomal aberrations detected by karyotyping. M-FISH proved to be more useful in identifying chromosomal partners involved in unbalanced translocations and in revealing greater complexity of 13q rearrangements. Most of the newly identified or refined recurrent alterations involved 1q, 13q and 3q (gains/losses), 7q and 18q (gains), or 6q (losses), suggesting that these secondary aberrations may play a role in lymphomagenesis. Several patterns of genomic aberrations were identified: 1q gains in BL, trisomies 7 in DLBCL, and 18q-translocations in adult non-BL. BCP-ALL usually displayed an 18q21 rearrangement. BL karyotypes were less complex and aneuploid than those of other MYC-rearranged lymphomas. BCP-ALL and DLBCL/BL were associated with a higher rate of early death than BL and DLBCL. These findings support the categorization of DLBCL/BL as a distinct entity and suggest that BL with CK are indeed different from other aggressive MYC-rearranged lymphomas, which usually show greater genetic complexity. © 2012 Wiley Periodicals, Inc.
Assuntos
Linfoma de Burkitt/genética , Aberrações Cromossômicas , Cromossomos Humanos , Rearranjo Gênico , Genes myc , Linfoma de Células B/genética , Cariótipo Anormal , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Hibridização in Situ Fluorescente , MasculinoRESUMO
OBJECTIVES: To study relationships between median wrist and forearm sonographic measurements and median nerve conduction studies. METHODS: The study population consisted of a prospective convenience sample of healthy adults. Interventions included high-resolution median nerve sonography and median motor and sensory nerve conduction studies. Main outcome measures included median motor nerve compound muscle action potential amplitude, distal latency, and conduction velocity; sensory nerve action potential amplitude and distal latency; and sonographic median nerve cross-sectional area. Median motor nerve and sensory nerve conduction studies of the index finger were performed using standard published techniques. A second examiner blinded to nerve conduction study results used a high-frequency linear array transducer to measure the cross-sectional area of the median nerve at the distal volar wrist crease (carpal tunnel inlet) and forearm (4 cm proximally), measured in the transverse plane on static sonograms. The outer margin of the median nerve was traced at the junction of the hypoechoic fascicles and adjacent outer connective tissue layer. RESULTS: Fifty median nerves were evaluated in 25 participants. The compound muscle action potential amplitude with wrist stimulation was positively related to the cross-sectional area, with the area increasing by 0.195 mm(2) for every millivolt increase in amplitude in the dominant hand (95% confidence interval, 0.020, 0.370 mm(2); P < .05) and 0.247 mm(2) in the nondominant hand (95% confidence interval, 0.035, 0.459 mm(2); P < .05). There was no significant linear association between the wrist median cross-sectional area and median motor and sensory distal latencies. Conduction velocity through the forearm was not significantly linearly associated with the forearm area or forearm-to-wrist area ratio (tapering ratio). The wrist area was inversely related to the sensory nerve action potential amplitude. CONCLUSIONS: Although associations were found between median nerve conduction study amplitudes and sonographic nerve measurements, they were not found for other parameters. Studying these relationships may increase our understanding of when to best use these procedures.
Assuntos
Aumento da Imagem/métodos , Nervo Mediano/diagnóstico por imagem , Nervo Mediano/fisiologia , Condução Nervosa/fisiologia , Ultrassonografia/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
Angiopoietins were thought to be endothelial cell-specific via the tie2 receptor. We showed that angiopoietin-1 (ang1) also interacts with integrins on cardiac myocytes (CMs) to increase survival. Because ang1 monomers bind and activate integrins (not tie2), we determined their function in vivo. We examined monomer and multimer expressions during physiological and pathological cardiac remodeling and overexpressed ang1 monomers in phenylephrine-induced cardiac hypertrophy. Cardiac ang1 levels (mRNA, protein) increased during postnatal development and decreased with phenylephrine-induced cardiac hypertrophy, whereas tie2 phosphorylations were unchanged. We found that most or all of the changes during cardiac remodeling were in monomers, offering an explanation for unchanged tie2 activity. Heart tissue contains abundant ang1 monomers and few multimers (Western blotting). We generated plasmids that produce ang1 monomers (ang1-256), injected them into mice, and confirmed cardiac expression (immunohistochemistry, RT-PCR). Ang1 monomers localize to CMs, smooth muscle cells, and endothelial cells. In phenylephrine-induced cardiac hypertrophy, ang1-256 reduced left ventricle (LV)/tibia ratios, fetal gene expressions (atrial and brain natriuretic peptides, skeletal actin, beta-myosin heavy chain), and fibrosis (collagen III), and increased LV prosurvival signaling (akt, MAPK(p42/44)), and AMPK(T172). However, tie2 phosphorylations were unchanged. Ang1-256 increased integrin-linked kinase, a key regulator of integrin signaling and cardiac health. Collectively, these results suggest a role for ang1 monomers in cardiac remodeling.
Assuntos
Angiopoietina-1/química , Angiopoietina-1/metabolismo , Cardiomegalia/prevenção & controle , Integrinas/metabolismo , Angiopoietina-1/genética , Animais , Sequência de Bases , Cardiomegalia/induzido quimicamente , Cardiomegalia/genética , Cardiomegalia/metabolismo , Linhagem Celular , Primers do DNA/genética , Células Endoteliais/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Fenilefrina/toxicidade , Fosforilação , Ligação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Estrutura Quaternária de Proteína , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor TIE-2/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Remodelação Ventricular/genética , Remodelação Ventricular/fisiologiaRESUMO
Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence in leukemic stem cells of the Philadelphia chromosome (Ph) and the formation of the BCR-ABL1 fusion. Untreated, the disease progresses to accelerate phase and blast crisis in which hematopoietic differentiation has become arrested. CML progression is frequently associated with cytogenetic evidence of clonal evolution, defined as additional chromosomal aberrations. We here report a CML resistant to tyrosine kinase inhibitors that rapidly progressed to blastic phase. At this time, array CGH performed on CD34(+) cells revealed cryptic partial deletions of both PRDM16 and RUNX1 and duplication of the der(21) chromosome. These genomic rearrangements were confirmed by FISH with probes targeting the deletion on chromosome 21 (24 kb), and with BAC probes flanking the deletion on 1p36 (220 kb). However, no cryptic t(1;21)(p36;q22) and/or RUNX1-PRDM16 were detected, suggesting that these deletions are the residual hallmarks of a more complex mechanism of chromosomal rearrangement, as indicated by the additional inversion of the region bounded by 1p36.32 and 1p36.12 breaks. At the molecular level, these abnormalities lead to the overexpression of the PR-domain negative oncogenic isoform of PRDM16, associated with two deleted copies within the runt domain of C-teminal aberrant RUNX1. These events are not detectable by conventional cytogenetic and molecular strategies, and may be of underestimated frequency in disease progression.
Assuntos
Cromossomos Humanos Par 21/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Proteínas de Ligação a DNA/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Proteínas de Fusão Oncogênica/genética , Deleção de Sequência , Fatores de Transcrição/genética , Adulto , Progressão da Doença , Feminino , Duplicação Gênica , Humanos , Modelos Genéticos , Hibridização de Ácido Nucleico , Proteínas de Fusão Oncogênica/metabolismo , Isoformas de Proteínas , Proteínas Recombinantes de Fusão/genética , Translocação Genética , Células Tumorais CultivadasRESUMO
Many published studies have indicated that various mechanisms could be involved in the genesis of variant chronic myelogeneous leukemia (CML) translocations. These are mainly one-step or two-step mechanisms, associated or not with deletions adjacent to the translocation junction on der(9) or der(22) chromosomes (or both). Based on the mechanism of genesis, it has been suggested that the complexity may affect the occurrence of ABL1 and BCR deletions (either or both), or may be associated with the CML disease course, and thus could determine the response to imatinib therapy. Through a retrospective molecular cytogenetic study of 41 CML patients with variant Philadelphia chromosome (Ph), we explored the genesis of these variant rearrangements and analyzed the correlation with deletion status and imatinib efficiency. Our results confirmed that the one-step mechanism is the most frequent, evidenced in 30 of 41 patients (73%); 3 patients demonstrated other more complex multistep events and 8 patients (19.5%) harbored ABL1 or BCR deletions that are not significantly associated with the complexity of translocation genesis. We also found no association between one-step, two-step, or multistep mechanisms and the response to imatinib therapy.
Assuntos
Deleção de Genes , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-abl/genética , Proteínas Proto-Oncogênicas c-bcr/genética , Pirimidinas/uso terapêutico , Translocação Genética , Benzamidas , Análise Citogenética , Feminino , Humanos , Mesilato de Imatinib , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Prognóstico , Proteínas Tirosina Quinases/antagonistas & inibidores , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: Two pathways, hyperdiploid and nonhyperdiploid, are proposed for progression to plasma cell neoplasia. Implication of monosomy 13 (Delta13) is unclear in monoclonal gammopathy of undetermined significance (MGUS), and data on DNA content of plasma cells [DNA index (DI)] are rare. EXPERIMENTAL DESIGN: We ascertained DI in 169 multiple myeloma (MM) and 96 MGUS patients. Interphase fluorescence in situ hybridization (FISH) coupled to cytoplasmic staining of specific Ig (cIg-FISH) was done to look for trisomies and to ascertain Delta13. RESULTS: Hyperdiploidy and hypodiploidy were found in 54% and 11.5% of MGUS patients and in 59.5% and 25% of MM patients, respectively. In MGUS patients tested using probes for odd chromosomes, cIg-FISH showed association between trisomies for chromosomes 3, 7, 9, 11, or 15 and hyperdiploidy. Delta13 was found in 45.3% and 24.6% of MM and MGUS patients, respectively. Most Delta13 cases observed in MGUS were found within hyperdiploid clones, 38% versus 11% in hypodiploid cases, in sharp contrast with the occurrence of Delta13 in MM patients, 31.9% and 76.3%, respectively. That peculiar distribution of Delta13 according to DI persisted with other thresholds used to ascertain hyperdiploidy, such as DI >or= 1.05. A strong relationship between IgA peak and hypodiploidy (P = 0.007) was only observed in MM, whereas lambda light chain was significantly associated with hypodiploidy in MGUS (P = 0.001) and MM (P = 0.05). Hyperdiploidy shows similar pattern in MGUS and MM. CONCLUSION: This fits well a hyperdiploid pathway leading to MM after a preceding MGUS stage. Yet-to-be-determined secondary event(s) needs to occur for the transition to MM, unrelated to changes in chromosome number or to loss of chromosome 13. In contrast, the "nonhyperdiploid" pathway needs to be clarified further because hypodiploidy is less common in MGUS than in MM and Delta13 is rare in hypodiploid MGUS patients compared with hypodiploid MM patients.
Assuntos
Cromossomos Humanos Par 13 , Diploide , Gamopatia Monoclonal de Significância Indeterminada/genética , Mieloma Múltiplo/genética , Adulto , Aberrações Cromossômicas , DNA/metabolismo , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Pessoa de Meia-Idade , Ploidias , Valores de Referência , Análise de Sequência de DNA , Translocação GenéticaRESUMO
In a case with secondary myelofibrosis occurring after essential thrombocythemia, cytogenetic analysis revealed an isolated translocation t(X;17)(q27;q22) in all cells. We found that a bacterial artificial chromosome (BAC) encompassing the breakpoint on chromosome 17 long arm contained only one gene, NOG. We therefore investigated the occurrence of this rare breakpoint in myeloproliferative disorders (MPDs). We identified three more patients with a 17q abnormality in MPDs: myelofibrosis with myeloid metaplasia (MMM); chronic myeloid leukemia positive for t(9;22)(q34;q11) with additional t(4;17)(p15;q22) at diagnosis; and myelofibrosis complicating polycythemia vera. All three cases exhibited a split of BACs containing NOG. The protein encoded by NOG, noggin, acts as an antagonist to bone morphogenetic secreted protein 2 and 4 (BMP2 and BMP4). A comparative analysis of gene expression on Agilent 22K oligonucleotide microarrays in purified CD34+ cells from the blood of MMM patients showed significant downregulation of BMPR2, BMPR1B, BMP2, and BMP8; upregulation of BMP3 and BMP10; and a trend to lower expression of NOG. Thus, given that expression and release of BMPs are important in the induction of osteosclerosis and angiogenic activity, the observed BMP deregulations could be triggered by potential NOG genetic alterations in the four cases here described, and may contribute to the myelofibrotic process characterized by bone marrow stromal reaction including collagen fibrosis, osteosclerosis, and angiogenesis.
Assuntos
Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Proteínas de Transporte/fisiologia , Transtornos Mieloproliferativos/genética , Mielofibrose Primária/genética , Adulto , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 17 , Cromossomos Humanos X , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Osteosclerose/genética , Translocação GenéticaRESUMO
Rearrangements of 6p are frequent in both myeloid and lymphoid malignant hematological disorders. High-mobility group AT-hook 2 (HMGA2) rearrangements have been described in myelofibrosis with myeloid metaplasia (MMM) and also in myelodysplasia. High-mobility group A proteins are nonhistone nuclear proteins that bind DNA and regulate the transcriptional activity of many genes. We used FISH, with bacterial artificial chromosome RP11-513I15 probe, to study 16 cases of myeloid malignancies with chromosome 6 short arm rearrangements, most of them following myeloproliferative disorders. Among these we found two 6p21.3 duplications and one 6p21.3 triplication involving HMGA1 in four cases of myelodysplasia with and without myelofibrosis. In these four cases, duplications and triplication were partially masked at the cytogenetic level by a derivative chromosome 6 resulting from translocation with another chromosome. HMGA1 proteins have been recently found overexpressed in human leukemias, but to our knowledge this is the first reported duplication of HMGA1.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 6 , Proteína HMGA1a/genética , Síndromes Mielodisplásicas/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Morphological changes of plasma cells (PC) are common in multiple myeloma (MM). Loss of round or oval nuclear shape has been related to cell malignancy in human, and we looked for the occurrence of such morphological change on PC from bone marrow (BM) smears in a retrospective series of 169 MM patients at diagnosis. Nuclear shape changes of PC differed according to the patients (notch, dumb-bell, folded or monocytoid appearance), even in the same patient; all subtypes were pooled and defined as PC with irregular nuclear shape (PCIN). A significant number of PCIN (>/=5% of all BMPC) was found at diagnosis in 20.7%. Median survival was of 22 months for patients with >/=5% PCIN, and 41 months for others (p=0.0001). Significant relationship was observed with prognostic parameters related intrinsic malignancy of the tumour process but not with beta-2-microglobulin (b2m). A clear-cut relationship was found also between PCIN and hypodiploidy (p=0.0001), but not with deletion of chromosome 13. This study emphasises the relationship between PCIN, an easy-to-ascertain marker of intrinsic malignancy of the tumour process, and adverse prognosis.
Assuntos
Aneuploidia , Células da Medula Óssea/patologia , Núcleo Celular/ultraestrutura , Mieloma Múltiplo/patologia , Idoso , Células da Medula Óssea/ultraestrutura , Núcleo Celular/patologia , Análise Citogenética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
We studied 94 clinically heterogeneous chronic myeloid leukemia (CML) patients and found that the duration of treatment with interferon-alpha (IFN-alpha) prior to imatinib therapy may not improve response to imatinib for patients in chronic phase but a shorter period between CML diagnosis and the initiation of imatinib is predictive for a better molecular response to therapy (p<0.05).
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Benzamidas , Esquema de Medicação , Feminino , Humanos , Mesilato de Imatinib , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-IdadeRESUMO
Chromosomal abnormalities are found by conventional cytogenetic (CC) analysis in about 50% of myelodysplastic syndromes (MDS) and 70% of acute myeloid leukemias (AML). When cytogenetic abnormalities are complex, multiplex fluorescence in situ hybridization (M-FISH) can help clarify complex chromosomal abnormalities and identify rearrangements with prognostic value or cryptic translocations, which could be preliminary steps in identifying new genes. We studied by M-FISH 28 cases of MDS and AML with complex chromosomal abnormalities, 10 of them were therapy-related. M-FISH allowed the characterization of unidentified chromosomal material in 26 cases (93%). One or several unbalanced rearrangements were observed in 27 cases (96%), generally interpreted as deletions or additional material by CC. Among those translocations, 4 involved 3 chromosomes. Eighteen cryptic translocations undetected by CC were found in 13 cases. By FISH analysis using locus specific probes, TP53 deletion, additional copies of MLL, and additional copies or deletions of RUNX1/AML1 were observed in 16, 4, and 3 cases, respectively. Thus, M-FISH is an important tool to characterize complex chromosomal abnormalities which identified unbalanced and cryptic translocations in 96% and 46% of the cases studied, respectively. Complementary FISH helped us identify involvement of TP53, MLL, and RUNX1/AML1 genes in 82% of cases, confirming their probable role in leukemogenesis.
Assuntos
Aberrações Cromossômicas , Hibridização in Situ Fluorescente/métodos , Leucemia Mieloide/genética , Síndromes Mielodisplásicas/genética , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-IdadeRESUMO
The purpose of this study was to investigate the mechanisms of referred pain observed in female patients with pain from the reproductive organs. We developed a model of inflammatory uterine pain in the rat. Inflammation of the uterus in rats pretreated with Evans Blue Dye resulted in dye extravasation in the skin over the abdomen, groin, lower back, thighs, perineal area and proximal tail, thus providing for the first time evidence for the trophic changes observed in the area of referred visceral pain in an animal model of uterine pain. The neuronal pathways mediating the observed dye extravasation in the skin after uterine inflammation may include dichotomizing afferent fibers, afferent-afferent interactions via a spinal cord pathway or a sympathetic reflex. This model will allow to gain further insight into the mechanisms of referred pain and the trophic changes observed in the area of referred pain in visceral disease.
Assuntos
Inflamação/complicações , Dor/fisiopatologia , Maturidade Sexual/fisiologia , Pele/inervação , Doenças Uterinas/complicações , Animais , Corantes , Modelos Animais de Doenças , Azul Evans , Extravasamento de Materiais Terapêuticos e Diagnósticos , Feminino , Dor/etiologia , Ratos , Ratos Sprague-Dawley , VíscerasRESUMO
BACKGROUND AND OBJECTIVES: MLL translocations generate a fusion gene between the 5' end of MLL and the 3' end of different partner genes. Several chromosomal mechanisms including complex and cryptic changes lead to these recombinations. Our objective was to analyze the molecular composition of chromosomes in complex karyotypes with specific MLL translocations. DESIGN AND METHODS: Fluorescence in situ hybridization (FISH) was performed in two acute leukemias (AL), one acute myeloid leukemia (AML) M5a, and one treatment-related-AL (t-AL), to investigate the nature of complex changes accompanying the respective t(9;11)(p22;q23)-MLL/AF9 and t(11;16)(q23;p13.3)-MLL/CBP. RESULTS: In the case with the MLL/AF9 chimeric transcript, duplication of a der(1) originated from an additional unbalanced translocation between the der(9)t(9;11) and a chromosome 1. The 5'AF9/3'MLL chimeric gene was present on both der(1). In the second case, there was a t(11;16)(q23;p13.3) producing one der(11) and two der(16) which derived from both homologs. One der(16) was present in multiple copies all containing the 5'CBP/3'MLL fusion gene. INTERPRETATION AND CONCLUSIONS: In both cases the 3' end of MLL was present in multiple copies. Mitotic recombination and non-disjunction may underlie the extra derivatives in both cases. In this genomic imbalance not only the 5'MLL but also the 3'end of MLL could play a critical role in the leukemic process.
Assuntos
Duplicação Gênica , Leucemia Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/genética , Doença Aguda , Adulto , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 16 , Cromossomos Humanos Par 9 , Análise Citogenética , Feminino , Humanos , Lactente , Masculino , Translocação GenéticaRESUMO
Recurrent chromosomal rearrangements involving the 11q23 region have been described in various hematologic malignancies. Among these rearrangements, translocations are the most common mechanism involving the mixed lineage leukemia gene (MLL). Few cases of insertion have been reported and, to our knowledge, none of them involved MLL and chromosome 1. We report a complex karyotype in a childhood acute myelomonocytic leukemia (AML M4) involving the 11q23 region with an insertion between chromosomes 1 and 11 in addition to a translocation between chromosomes 11 and 22. This translocation was clarified by fluorescence in situ hybridization (FISH) analysis: 46,XY,ins(1;11)(q22 approximately q23;q13q23),t(11;22)(q13;q11 approximately q12). This finding also underlines the complementary contribution of conventional cytogenetic and FISH analysis to detect karyotypic complex abnormalities.
Assuntos
Cromossomos Humanos Par 22/genética , Elementos de DNA Transponíveis/genética , Leucemia Mielomonocítica Aguda/genética , Humanos , Hibridização In Situ , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , MasculinoRESUMO
The majority of non-Hodgkin lymphomas of B-cell type (B-NHL) exhibit chromosomal abnormalities including many types of reciprocal translocations closely related to specific histopathologic entities. The t(9;14)(p13;q32) has been recognized as a primary genetic event directly involved in the development of lymphoplasmacytic lymphoma. In the 14 published cases, the t(9;14)(p13;32) seems to delineate a variety of low-grade B-cell disorders characterized by a common clinical history and immunopathologic similarities. We report here three new cases presenting a t(9;14)(p13;q32) with other chromosomal abnormalities which have been referred to as B-cell low-grade or high-grade malignant lymphoproliferative disorders. Two of these cases showed diffuse large B cell lymphoma morphology and two patients had a favorable clinical outcome. These data suggest that t(9;14)(p13;q32) is not restricted to low-grade lymphoma.
Assuntos
Cromossomos Humanos Par 14 , Cromossomos Humanos Par 9 , Linfoma de Células B/genética , Translocação Genética , Idoso , Feminino , Humanos , Imuno-Histoquímica , Cariotipagem , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Among cytogenetic studies of 205 patients diagnosed as myelofibrosis with myeloid metaplasia, we found seven cases with structural abnormalities of the long arm of chromosome 12. The karyotype showed six balanced translocations, that is, t(4;12)(q33;q21), t(5;12)(p14;q21), t(1;12)(q22;q24), t(12;17)(q24;q11), t(7;12) (p11;q24), and t(1;12)(p12;q24), as well as other cytogenetic abnormalities such as del(12)(q21;q24) and inv(12) (p12q24). Some isolated cases involving the 12q21 region have also been described in the literature. Importance of rearrangement of chromosome 12 in 12q21 or 12q24 is underlined by the authors suggesting a proto-oncogene accountable mechanism of leukemogenesis.
Assuntos
Células da Medula Óssea/patologia , Aberrações Cromossômicas , Cromossomos Humanos Par 12 , Leucemia Mieloide Aguda/genética , Mielofibrose Primária/genética , Translocação Genética , Adulto , Idoso , Mapeamento Cromossômico , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/complicações , Mielofibrose Primária/patologia , Proto-Oncogene MasRESUMO
Polycythemia vera (PV) is a chronic myeloproliferative disease characterized by an increase of total red cell volume; in 10% to 15% of cases, bone marrow fibrosis complicates the course of the disease after several years, resulting in a hematologic picture mimicking myelofibrosis with myelocytic metaplasia (MMM). This condition is known as post polycythemic myelofibrosis (PPMF). Among 30 patients with PPMF followed in Northern France, 27 (90%) expressed one or two abnormal clones in myelocytic cell cultures. Of these, 19 (70%) had partial or complete trisomy 1q. This common anomaly either resulted from unbalanced translocations with acrocentric chromosomes, that is, 13, 14, and 15, or other chromosomes, that is, 1, 6, 7, 9, 16, 19, and Y, or from partial or total duplication of long arm of chromosome 1. A single patient had an isochromosome 1q leading to tetrasomy 1q. In all cases, a common trisomic region spanning 1q21 to 1q32 has been identified. Given that most patients had previously received chemotherapy or radio-phosphorus to control the polycythemic phase of their disease, this study illustrates the increased frequency of cytogenetic abnormalities after such treatments: 90% versus 50% in de novo MMM. Moreover, karyotype can be used to distinguish PPMF-where trisomy 1q is the main anomaly-from primary MMM where trisomy 1q is rare and deletions 13q or 20q are far more common. Whether trisomy 1q is or is not a secondary event remains a matter of debate, as well as the role of cytotoxic treatments.
Assuntos
Aberrações Cromossômicas , Policitemia Vera/complicações , Mielofibrose Primária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Criança , Bandeamento Cromossômico , Cromossomos Humanos/genética , Cromossomos Humanos/ultraestrutura , Progressão da Doença , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Policitemia Vera/patologia , Mielofibrose Primária/etiologia , Mielofibrose Primária/mortalidade , Mielofibrose Primária/patologia , Análise de SobrevidaRESUMO
In order to evaluate the prognostic factors for progression and survival in patients with a low tumor mass asymptomatic multiple myeloma (MM), we studied 59 patients who had a long term follow-up. Cytogenetic abnormalities (using conventional cytogenetics) were observed in 14 out of 45 analyzable patients (31%). An abnormal karyotype and a bone marrow (BM) plasmacytosis > 15% were found to be adverse prognostic factors for progression in univariate and multivariate analysis.
Assuntos
Medula Óssea/patologia , Aberrações Cromossômicas , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Fatores de TempoRESUMO
The pleural space is modeled in two dimensions as a thin layer of fluid separating a deformable membrane and a rigid surface containing a bump. We computed the steady-state membrane configuration and fluid pressure distribution during relative sliding of the two surfaces. For physiologically relevant values of membrane tension, shear flow-induced pressures near the bump and far-field pressure gradients are similar to those measured in vivo within the pleural space (e.g. Lai-Fook et al.) [J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 56 (1984) 1633-1639]. Deformation of the membrane over the bump suggests that the pressure field generated by the sliding motion promotes an even layer of fluid in the pleural space, preventing asperities from touching. Results also suggest a possible mechanism for pleural fluid redistribution during breathing, whereby irreversible fluid motion is associated with the deformability of the membrane.