RESUMEN
The t(9;22)(q34;q11), generating the Philadelphia chromosome (Ph), is found in more than 90% of patients with chronic myeloid leukemia (CML) and in 15-30% of adults with acute lymphoblastic leukemia (ALL). Different groups have recently described the presence of large genomic deletions adjacent to the translocation breakpoint on the derivative chromosome 9 in 9-16% of CML patients. In the present paper, we report a FISH study of 45 Ph+ adult ALL patients with the aim of investigating the presence of deletions on derivative chromosome 9. In four (9%) of 45 cases, all showing an M-bcr, we detected deletions on der(9). The frequency of deletions we observed is similar to that reported in CML patients. The association of an M-bcr breakpoint and deletions appears significant (P=0.03). Some authors have suggested a very low incidence of der(9) deletions in ALL. This discrepancy can be explained by taking into account the low percentage of M-bcr ALL patients in the latter study (18%) compared to the present one (44%).
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 9 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Tirosina Quinasas , Proteínas Proto-Oncogénicas , Adulto , Femenino , Humanos , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Persona de Mediana Edad , Proteínas Oncogénicas/genética , Proteínas Proto-Oncogénicas c-bcr , Eliminación de SecuenciaRESUMEN
We report a case of acute myeloid leukemia (AML-M2) expressing myeloperoxidase (MPO) but no myeloid antigens. A few cases with this discordant phenotype have been reported and an association has been suggested between the lack of CD13 and CD33 in MPO positive AML and the presence of t(8;21). Cytogenetic and molecular analyses performed in our case showed 48,XY,+Y,+8,t(2;9)(q14;p12). We believe that combined approaches can contribute to detect particular AL cases like the present one, that confirms the heterogeneity of AML. However, further studies are needed to clarify the relationship between phenotypic aberrations and cytogenetic abnormalities.
Asunto(s)
Cromosomas Humanos Par 2 , Cromosomas Humanos Par 9 , Leucemia Mieloide Aguda/genética , Peroxidasa/metabolismo , Translocación Genética , Adulto , Anciano , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Antígenos CD13/análisis , Niño , Humanos , Leucemia Mieloide Aguda/enzimología , Leucemia Mieloide Aguda/inmunología , Persona de Mediana Edad , Lectina 3 Similar a Ig de Unión al Ácido SiálicoRESUMEN
On the basis of a survey of the literature, an etiopathogenetic classification of biliary peritonitis is presented, with particular reference to forms without perforation. The variability of clinical picture and the difficulties of correct pre-operative diagnosis explain the mortality rate of 30-50%.
Asunto(s)
Bilis , Peritonitis/etiología , Enfermedades de las Vías Biliares/complicaciones , Diagnóstico Diferencial , Humanos , Peritonitis/diagnóstico , Peritonitis/fisiopatología , Rotura EspontáneaRESUMEN
Recently it has been demonstrated that ten-eleven-translocation-2 (TET2) gene alterations may represent a crucial event in the pathogenesis of various myeloid malignancies. To date, the loss of TET2 function has been solely ascribed to mutations in the gene coding region. In this study, we report a chronic myeloid leukemia (CML) case showing a TET2 single copy partial deletion associated to a t(4;6;11) rearrangement, appearing during the progression of the disease and responsible for a decreased TET2 gene expression. A putative role for TET2 haploinsufficiency in this patient's CML progression is discussed.
Asunto(s)
Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 4/genética , Cromosomas Humanos Par 6/genética , Proteínas de Unión al ADN/genética , Eliminación de Gen , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Proteínas Proto-Oncogénicas/genética , ADN de Neoplasias/genética , Dioxigenasas , Progresión de la Enfermedad , Estudios de Seguimiento , Proteínas de Fusión bcr-abl/genética , Reordenamiento Génico , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
A crucial role of segmental duplications (SDs) of the human genome has been shown in chromosomal rearrangements associated with several genomic disorders. Limited knowledge is yet available on the molecular processes resulting in chromosomal rearrangements in tumors. The t(9;22)(q34;q11) rearrangement causing the 5'BCR/3'ABL gene formation has been detected in more than 90% of cases with chronic myeloid leukemia (CML). In 10-18% of patients with CML, genomic deletions were detected on der(9) chromosome next to translocation breakpoints. The molecular mechanism triggering the t(9;22) and deletions on der(9) is still speculative. Here we report a molecular cytogenetic analysis of a large series of patients with CML with der(9) deletions, revealing an evident breakpoint clustering in two regions located proximally to ABL and distally to BCR, containing an interchromosomal duplication block (SD_9/22). The deletions breakpoints distribution appeared to be strictly related to the distance from the SD_9/22. Moreover, bioinformatic analyses of the regions surrounding the SD_9/22 revealed a high Alu frequency and a poor gene density, reflecting genomic instability and susceptibility to rearrangements. On the basis of our results, we propose a three-step model for t(9;22) formation consisting of alignment of chromosomes 9 and 22 mediated by SD_9/22, spontaneous chromosome breakages and misjoining of DNA broken ends.
Asunto(s)
Cromosomas Humanos Par 22 , Cromosomas Humanos Par 9 , Duplicación de Gen , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Translocación Genética , Biología Computacional , HumanosAsunto(s)
Bilis , Peritonitis/etiología , Animales , Bilis/análisis , Bilis/metabolismo , Cateterismo , Perros , Femenino , Vesícula Biliar/efectos de los fármacos , Vesícula Biliar/patología , Ligadura , Masculino , Conductos Pancreáticos/cirugía , Jugo Pancreático/análisis , Jugo Pancreático/metabolismo , Secretina/administración & dosificaciónRESUMEN
In the present paper we report pericentric chromosome 8 inversions in two (2.4%) of 82 acute myeloid leukemia (AML) cases characterized by the 5'RUNX1/3'CBFA2T1 fusion gene. Molecular cytogenetic characterization was achieved using appropriate bacterial artificial chromosome (BAC) and P1 artificial chromosome (PAC) probes in fluorescence in situ hybridization (FISH) experiments. In these two cases the fusion gene was detected on the der(8) short arm, resulting from a pericentric chromosome 8 inversion followed by a t(8;21) rearrangement. These results suggest that heterogeneous mechanisms can lead to the generation of the 5'RUNX1/3'CBFA2T1chimeric gene.
Asunto(s)
Inversión Cromosómica , Cromosomas Humanos Par 8 , Proteínas de Unión al ADN/genética , Leucemia Mieloide/genética , Proteínas Proto-Oncogénicas/genética , Factores de Transcripción/genética , Enfermedad Aguda , Adulto , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Proteína 1 Compañera de Translocación de RUNX1RESUMEN
The Purdue Post-traumatic Stress Disorder Scale is a 15-item self-report instrument based on the DSM-III diagnostic criteria for post-traumatic stress disorder. This scale is a quick, easily administered, measure of psychological reactions to a traumatic event. The goal of the present report is to validate this instrument for use as a measure of long-lasting combat stress reactions of American Vietnam veterans. The PPS demonstrated a high degree of internal consistency with a Cronbach's coefficient alpha of 0.94. The PPS demonstrated construct validity through significant correlations with other self-report measures of combat experience and residual psychological distress, and through a factor analysis yielding three factors, labeled as arousal, avoidance, and the global perception of distress. Results support further use of the Purdue Post-traumatic Stress Scale as a research instrument for assessing the long-term impact of a traumatic event.
Asunto(s)
Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Trastornos por Estrés Postraumático/diagnóstico , Veteranos/psicología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , VietnamRESUMEN
The EVI1 proto-oncogene encodes a nuclear zinc finger protein that acts as a transcription repressor factor. In myeloid leukemia it is often activated by chromosomal rearrangements involving band 3q26, where the gene has been mapped. Here we report two leukemia cases [a chronic myeloid leukemia blast crisis (CML-BC) and an acute myeloid leukemia (AML) M4] showing a t(3;7)(q26;q21) translocation in a balanced and unbalanced form, respectively. Fluorescent in situ hybridization (FISH) analysis revealed that both patients showed a breakpoint on chromosome 3 inside the clone RP11-33A1 containing the EVI1 oncogene and, on chromosome 7, inside the clone RP11-322M5, partially containing the CDK6 oncogene which is a D cyclin-dependent kinase gene, observed to be overexpressed and disrupted in many hematological malignancies. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed overexpression of EVI1 in both cases, but excluded the presence of any CDK6/ EVI1 fusion transcript. CDK6 expression was also detected. Together, these data indicate that EVI1 activation is likely due not to the generation of a novel fusion gene with CDK6 but to a position effect dysregulating its transcriptional pattern.