RESUMO
AIM: Ischemic gastritis is poorly known by physicians and is often fatal if not correctly diagnosed. Here, we report on the clinical, endoscopic and imaging features and treatment outcomes for five ischemic gastritis patients. METHODS: This was a retrospective, single-centre study of patients treated for ischemic gastritis between January 2009 and April 2012. All patients underwent transluminal angioplasty or open revascularization surgery. RESULTS: Five patients (4 men, 1 female) were included in the present study. The condition was diagnosed in two cases of peritonitis with gastric or duodenal perforation, two cases of acute epigastric pain and one case of gastric bleeding, profuse vomiting and hypovolemic shock. Three of the five patients had endoscopically proven gastric ulcerations or necrosis. A computed tomography scan contributed to the diagnosis in all cases. The symptoms resolved in all cases after gastric revascularization via an aortohepatic bypass (N.=1), a renohepatic bypass (N.=1), a retrograde iliosuperior mesenteric bypass (N.=2) with associated celiac artery angioplasty (N.=1) and celiac and superior mesenteric artery angioplasty (N.=1). During follow-up, three patients died of starvation due to short bowel syndrome (N.=1) or metastatic lung cancer (N.=2). CONCLUSION: Ischemic gastritis is a component of celiac territory ischemia syndrome and is closely associated with chronic or acute mesenteric ischemia. Computed tomography always informs the diagnosis. The rapid healing observed here after revascularization confirmed the ischemic nature of the condition and the inappropriateness of gastric resection in this context.
Assuntos
Gastrite/etiologia , Isquemia/etiologia , Estômago/irrigação sanguínea , Artéria Celíaca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SíndromeRESUMO
Myeloproliferative neoplasms are frequently associated with aberrant constitutive tyrosine kinase (TK) activity resulting from chimaeric fusion genes or point mutations such as BCR-ABL1 or JAK2 V617F. We report here the cloning and functional characterization of two novel fusion genes BCR-RET and FGFR1OP-RET in chronic myelomonocytic leukemia (CMML) cases generated by two balanced translocations t(10;22)(q11;q11) and t(6;10)(q27;q11), respectively. The two RET fusion genes leading to the aberrant activation of RET, are able to transform hematopoietic cells and skew the hematopoietic differentiation program towards the monocytic/macrophage lineage. The RET fusion genes seem to constitutively mimic the same signaling pathway as RAS mutations frequently involved in CMML. One patient was treated with Sorafenib, a specific inhibitor of the RET TK function, and demonstrated cytological and clinical remissions.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Leucemia Mielomonocítica Crônica/patologia , Monócitos/citologia , Proteínas Proto-Oncogênicas c-ret/genética , Sequência de Bases , Primers do DNA , Humanos , Hibridização in Situ Fluorescente , Leucemia Mielomonocítica Crônica/genética , Mutação Puntual , Reação em Cadeia da Polimerase/métodos , Translocação GenéticaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Adulto , Idoso , Azacitidina/administração & dosagem , Feminino , Humanos , Cariotipagem , Lenalidomida , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Risco , Talidomida/administração & dosagem , Talidomida/análogos & derivadosAssuntos
Leucemia Mieloide Aguda/genética , Mutação , Adolescente , Criança , Pré-Escolar , Feminino , Genes do Tumor de Wilms , Genes ras , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/mortalidade , Masculino , Análise Multivariada , Proteína de Leucina Linfoide-Mieloide/genética , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
The t(8;16)(p11;p13) is a rare translocation involved in de novo and therapy-related myelomonocytic and monocytic acute leukemia. It fuses two genes encoding histone acetyltransferases (HATs), MYST3 located at 8p11 to CREBBP located at 16p13. Variant translocations involve other HAT-encoding genes such as EP300, MYST4, NCOA2 or NCOA3. MYST3-linked acute myeloid leukemias (AMLs) share specific clinical and biological features and a poor prognosis. Because of its rarity, the molecular biology of MYST3-linked AMLs remains poorly understood. We have established the genome and gene expression profiles of a multicentric series of 61 M4/M5 AMLs including 18 MYST3-linked AMLs by using array comparative genome hybridization (aCGH) (n=52) and DNA microarrays (n=44), respectively. We show that M4/5 AMLs have a variety of rare genomic alterations. One alteration, a gain of the MYB locus, was found recurrently and only in the MYST3-linked AMLs (7/18 vs 0/34). MYST3-AMLs have also a specific a gene expression profile, which includes overexpression of MYB, CD4 and HOXA genes. These features, reminiscent of T-cell acute lymphoid leukemia (ALL), suggest the targeting of a common T-myeloid progenitor.
Assuntos
Perfilação da Expressão Gênica/métodos , Genes myb/genética , Histona Acetiltransferases/genética , Leucemia Mielomonocítica Aguda/genética , Antígenos CD4/genética , Hibridização Genômica Comparativa , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Proteínas de Homeodomínio/genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Proto-Oncogênicas c-myb/genéticaRESUMO
Neurological crises do not occur in patients with tyrosinaemia type I treated with NTBC. We report an 8 month-old boy with severe neurological crisis after interruption of NTBC treatment including progressive ascending polyneuropathy and diaphragmatic paralysis, arterial hypertension, respiratory distress requiring mechanical ventilation who later also developed impaired liver function and tubulopathy. After re-introduction of NTBC the patient slowly regained normal neurological functions and recovered completely.
Assuntos
Cicloexanonas/administração & dosagem , Inibidores Enzimáticos/administração & dosagem , Nitrobenzoatos/administração & dosagem , Polineuropatias/etiologia , Paralisia Respiratória/etiologia , Tirosinemias/tratamento farmacológico , Esquema de Medicação , Humanos , Hipertensão/etiologia , Lactente , Masculino , Adesão à Medicação , Polineuropatias/fisiopatologia , Polineuropatias/terapia , Respiração Artificial , Insuficiência Respiratória/etiologia , Paralisia Respiratória/fisiopatologia , Paralisia Respiratória/terapia , Tirosinemias/complicações , Tirosinemias/diagnósticoRESUMO
A series of 38 patients with acute myeloblastic leukemia (AML) with 49 or more chromosomes and without structural abnormalities was selected within the Groupe Francophone de Cytogénétique Hématologique (GFCH) to better define their characteristics. The median age of the patients was 65 years, and all FAB subtypes were represented. Although all chromosomes were gained, some seems to prevail: chromosome 8 (68%), 21 (47%), 19 (37%), and 13 and 14 (34% each). Since MLL rearrangement leads patients in a group with an unfavorable prognosis, search for cryptic rearrangements of MLL was performed in 34 patients and showed abnormalities in 5 (15%). When we applied the most frequent definition of complex karyotypes (three or more abnormalities), all patients with high hyperdiploid AML fall in the unfavorable category. Among the 18 patients without MLL rearrangement receiving an induction therapy, 16 (89%) reached CR and 6 (33%) were still alive after a 31-month median follow-up (14-61 months). Although this study was retrospective, these results suggest that high hyperdiploid AML without chromosome rearrangement seems to be a subgroup of uncommon AML (less than 1%), and may be better classified in the intermediate prognostic group.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos/genética , Leucemia Mieloide/genética , Ploidias , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Rearranjo Gênico , Histona-Lisina N-Metiltransferase , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/epidemiologia , Masculino , Pessoa de Meia-Idade , Proteína de Leucina Linfoide-Mieloide/genética , Prognóstico , Estudos Prospectivos , Estudos RetrospectivosAssuntos
Cromossomos Humanos Par 16/ultraestrutura , Cromossomos Humanos Par 8/ultraestrutura , Histona Acetiltransferases/genética , Leucemia Monocítica Aguda/genética , Fusão Oncogênica , Proteínas de Fusão Oncogênica/genética , Transativadores/genética , Translocação Genética , Idoso , Sequência de Aminoácidos , Sequência de Bases , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 8/genética , Éxons/genética , Evolução Fatal , Feminino , Regulação Leucêmica da Expressão Gênica/genética , Regulação Leucêmica da Expressão Gênica/fisiologia , Histona Acetiltransferases/química , Histona Acetiltransferases/fisiologia , Humanos , Íntrons/genética , Dados de Sequência Molecular , Coativador 3 de Receptor Nuclear , Proteínas de Fusão Oncogênica/química , Estrutura Terciária de Proteína , Transativadores/química , Transativadores/fisiologia , Transcrição GênicaRESUMO
We report a new case of transient myeloproliferative disorder (TMD) in a non Down syndrome neonate. The cytogenetic and molecular studies within from the blood blast cells identified a trisomy 21 and a partial deletion in exon 2 of the transcription factor GATA1. Spontaneous regression of the TMD was achieved at the age of 1 month as the clonal and molecular abnormalities. A survey by periodic cytological examinations of peripheral blood cells and GATA1 mutation analysis was instituted since three years and has not detected up to date acute leukaemia.
Assuntos
Doenças do Prematuro/diagnóstico , Recém-Nascido Prematuro , Transtornos Mieloproliferativos/diagnóstico , Doenças em Gêmeos , Síndrome de Down/genética , Éxons/genética , Seguimentos , Fator de Transcrição GATA1/genética , Deleção de Genes , Humanos , Recém-Nascido , Masculino , Mutação/genética , Remissão Espontânea , Gêmeos DizigóticosRESUMO
Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRbeta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.
Assuntos
Proteínas de Homeodomínio/genética , Leucemia-Linfoma de Células T do Adulto/genética , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Adolescente , Adulto , Criança , Deleção Cromossômica , Inversão Cromossômica , Feminino , Rearranjo Gênico do Linfócito T , Proteínas Homeobox A10 , Humanos , Imunofenotipagem , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/fisiopatologia , Masculino , Pessoa de Meia-Idade , Receptor Notch1/genética , Ativação Transcricional , Translocação GenéticaRESUMO
The NUP98 gene is fused with 19 different partner genes in various human hematopoietic malignancies. In order to gain additional clinico-hematological data and to identify new partners of NUP98, the Groupe Francophone de Cytogénétique Hématologique (GFCH) collected cases of hematological malignancies where a 11p15 rearrangement was detected. Fluorescence in situ hybridization (FISH) analysis showed that 35% of these patients (23/66) carried a rearrangement of the NUP98 locus. Genes of the HOXA cluster and the nuclear-receptor set domain (NSD) genes were frequently fused to NUP98, mainly in de novo myeloid malignancies whereas the DDX10 and TOP1 genes were equally rearranged in de novo and in therapy-related myeloid proliferations. Involvement of ADD3 and C6ORF80 genes were detected, respectively, in myeloid disorders and in T-cell acute lymphoblastic leukemia (T-ALL), whereas the RAP1GDS1 gene was fused to NUP98 in T-ALL. Three new chromosomal breakpoints: 3q22.1, 7p15 (in a localization distinct from the HOXA locus) and Xq28 were detected in rearrangements with the NUP98 gene locus. The present study as well as a review of the 73 cases previously reported in the literature allowed us to delineate some chromosomal, clinical and molecular features of patients carrying a NUP98 gene rearrangements.
Assuntos
Neoplasias Hematológicas/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Translocação Genética/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Citogenética , Feminino , França , Proteínas de Homeodomínio/genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Pessoa de Meia-Idade , Receptores Citoplasmáticos e Nucleares/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Sociedades MédicasAssuntos
Proteínas de Ciclo Celular/genética , Cromossomos Humanos Par 8 , Cromossomos Humanos Par 9 , Fusão Gênica , Linfoma de Células T/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Translocação Genética , Adulto , Autoantígenos , Humanos , Janus Quinase 2 , Linfoma de Células T/enzimologia , MasculinoRESUMO
AIMS: Medulloblastoma (MB), a kind of infratentorial primitive neuroectodermal tumour (PNET), is the most frequent malignant brain tumour in childhood. In contrast, supratentorial PNET (sPNET) are very infrequent tumours, but they are histologically similar to MB, although they present a worse clinical outcome. We investigated the differences in genetic abnormalities between sPNET and MB. METHODS AND RESULTS: We analysed 20 central PNET (14 MB and six sPNET) by conventional comparative genomic hybridization (CGH) in order to determine whether a different genetic profile for each tumour exists. Isochromosome 17q was detected in four of the 14 MB cases, but not in any sPNET. Gains at 17q and 7 happened more frequently in MB, and those at 1q in sPNET. Losses at chromosome 10 were detected only in MB, while losses at 16p and 19p happened more frequently in sPNET. A new amplification site, on 4q12, was detected in two MB. CONCLUSIONS: Central PNET are a heterogeneous group of tumours from the genetic point of view. The present and previous data, together with further results from larger series, might contribute to the establishment of specific treatments for supratentorial and infratentorial PNET.
Assuntos
Neoplasias Encefálicas/genética , Heterogeneidade Genética , Neoplasias Infratentoriais/genética , Tumores Neuroectodérmicos Primitivos/genética , Neoplasias Supratentoriais/genética , Neoplasias Encefálicas/patologia , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 16 , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 4 , Cromossomos Humanos Par 7 , Humanos , Neoplasias Infratentoriais/patologia , Meduloblastoma/genética , Meduloblastoma/patologia , Tumores Neuroectodérmicos Primitivos/patologia , Hibridização de Ácido Nucleico , Neoplasias Supratentoriais/patologiaAssuntos
Proteínas de Ciclo Celular/genética , Leucemia Eritroblástica Aguda/genética , Transtornos Mieloproliferativos/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Translocação Genética , Adulto , Autoantígenos , Criança , Cromossomos Humanos Par 8/genética , Cromossomos Humanos Par 9/genética , Feminino , Humanos , Janus Quinase 2 , Masculino , Pessoa de Meia-IdadeRESUMO
To accurately estimate the incidence of HOX11L2 expression, and determine the associated cytogenetic features, in T-cell acute lymphoblastic leukemia (T-ALL), the Groupe Français de Cytogénétique Hématologique (GFCH) carried out a retrospective study of both childhood and adult patients. In total, 364 patients were included (211 children
Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 5/genética , Proteínas de Homeodomínio/genética , Leucemia-Linfoma de Células T do Adulto/genética , Proteínas Oncogênicas/genética , Translocação Genética , Adolescente , Adulto , Criança , Pré-Escolar , Aberrações Cromossômicas , Células Clonais , Feminino , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Ploidias , Proteínas Proto-Oncogênicas , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaAssuntos
Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 22/genética , Proteínas de Ligação a DNA/genética , Leucemia Mieloide/diagnóstico , Proteínas de Fusão Oncogênica/genética , Proteínas/genética , Proteínas de Ligação a RNA , Translocação Genética , Doença Aguda , Antígenos CD/análise , Pré-Escolar , Humanos , Leucemia Mieloide/genética , Neoplasia Residual , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sensibilidade e Especificidade , TransativadoresRESUMO
We studied a stratified cohort of 51 childhood B-lineage acute lymphoblastic leukemias (B-ALLs) to evaluate the efficiency of spectral karyotyping (SKY) in the detection of chromosome aberrations previously diagnosed using chromosome banding and/or reverse transcriptase polymerase chain reaction. Despite the small number of cases analyzed, several important features emerge from the study: (a) The result of banding analysis was revised in two-thirds of the cases. Eighty-three chromosome anomalies previously undetected or not characterized using chromosome banding were identified by spectral karyotyping, even in patients with apparently normal karyotypes. (b) All hyperdiploidy cases showed one or more extra copies of chromosomes X, 14, and 21. (c) Two hidden rearrangements, a t(7;12)(?p12;p13), and a new translocation, a t(9;12)(q31;p13), both involving the TEL gene, were characterized. (d) Some cryptic rearrangements, such as the der(21) t(12;21) translocation, remained undetected. (e) No new recurrent chromosome anomalies were discovered with this technique. In conclusion, the present study confirms the efficiency of the SKY technique in resolving and characterizing many complex chromosome anomalies seen in childhood B-ALLs, but it raises questions about the ability of this technique to detect cryptic rearrangements, such as the t(12;21) translocation.
Assuntos
Linfoma de Burkitt/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Linfoma de Burkitt/patologia , Criança , Aberrações Cromossômicas/genética , Bandeamento Cromossômico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Microscopia de Fluorescência , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Translocação Genética/genéticaAssuntos
Cromossomos Humanos Par 22/genética , Cromossomos Humanos Par 9/genética , Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Ativação Linfocitária , Translocação Genética , Idoso , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Proteínas de Fusão Oncogênica/genéticaRESUMO
Two cases of papillary renal cell carcinoma (RCC) with a karyotype 46,X,t(X;1)(p11.2;q21) in two female patients aged 9 and 29 years are reported. These observations, and the review of the 17 reported cases with a translocation at band Xp11 confirm that this abnormality delineates a clinicopathological entity within the classical papillary RCC, characterized by the early age of occurrence and, probably, distinct histological features. Including these two new female cases, the sex ratio in cases with t(X;1) appears similar to that observed in the other papillary RCC.