Linfomas con reordenamiento de MYC distintos del linfoma de Burkitt: comparación entre R-CHOP y la inmunoquimioterapia tipo Burkitt / MYC-rearranged lymphomas other than Burkitt: Comparison between R-CHOP and Burkitt-type immunochemotherapy

Antecedentes y objetivo: Los linfomas con reordenamiento de MYC (MYC-R) diferentes al linfoma de Burkitt (LB) son muy agresivos, con un pronóstico desfavorable cuando se tratan con regímenes estándar. El objetivo del estudio fue investigar las características y el resultado de una serie de linfomas MYC-R, comparando los resultados del tratamiento de los regímenes basados en R-CHOP y un régimen intensivo específico para LB (BURKIMAB). Pacientes y métodos: Estudio retrospectivo de pacientes diagnosticados de MYC-R. Se evaluaron las translocaciones de MYC, BCL2 y BCL6 mediante hibridación in situ fluorescente. Se trató a los pacientes, bien con inmunoquimioterapia basada en R-CHOP, bien con el régimen tipo Burkitt, BURKIMAB. Resultados: Se estudiaron 34 casos de linfomas MYC-R: 21 tratados con R-CHOP y 13 tratados con BURKIMAB. No se produjeron diferencias en cuanto a tasa de RC; 45% (9/20) para R-CHOP y 42% (5/12) para BURKIMAB (p=0,99). Aunque la supervivencia global (SG) y la supervivencia libre de progresión (SLP) de los pacientes tratados con BURKIMAB fueron mejores que las de los pacientes tratados con R-CHOP (SG a 3 años: 46 frente a 24%; SLP a 3 años: 46 frente a 10%), las diferencias no fueron estadísticamente significativas. Conclusión: Los linfomas MYC-R muestran resultados desfavorables, aun cuando se tratan con inmunoquimioterapia intensiva para LB (AU)

Background and objective: MYC-rearranged (MYC-R) lymphomas other than Burkitt lymphoma (BL) are very aggressive, with poor prognosis when treated with standard regimens. We aimed to study the characteristics and outcome of a series of MYC-R lymphomas comparing the treatment results between R-CHOP based and a specific intensive regimen for BL (BURKIMAB). Patients and methods: Retrospective study of patients diagnosed with MYC-R. Translocations of MYC, BCL2 and BCL6 were evaluated by fluorescent in situ hybridization. Patients were treated with either, R-CHOP based immunochemotherapy or the Burkitt type regimen, BURKIMAB. Results: Thirty-four MYC-R lymphoma cases were studied: 21 treated with R-CHOP and 13 treated with BURKIMAB. There were no differences in CR rate; 45% (9/20) for R-CHOP and 42% (5/12) for BURKIMAB (P=.99). Although overall survival (OS) and progression free survival (PFS) of BURKIMAB-treated patients were better than those of R-CHOP-treated (3y-OS: 46 vs. 24%; 3y-PFS: 46 vs. 10%), the differences were not statistically significant. Conclusion: MYC-R lymphomas show poor outcomes even when treated with intensive immunochemotherapy for BL (AU)

Reordenamiento de MYC en los linfomas B agresivos: un gran reto terapéutico / MYC rearrangement in aggressive B-cell lymphomas: A major therapeutic challenge

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Alteraciones en el número de copias en pacientes adultos con leucemia linfoblástica aguda B madura, tratados con inmunoquimioterapia específica / Copy number alterations in adult patients with mature B acute lymphoblastic leukemia treated with specific immunochemotherapy

Fundamento y objetivo: A diferencia del linfoma de Burkitt, las alteraciones moleculares distintas a los reordenamientos de C-MYC apenas se han estudiado en pacientes con leucemia linfoblástica aguda B (LLA-B) madura. El objetivo de este estudio fue analizar la frecuencia y el significado pronóstico de las copy number alterations (CNA, «alteraciones del número de copias») en genes clave de la diferenciación de los linfocitos, ciclo celular y supresores de tumores en pacientes adultos. Pacientes y métodos: Se analizaron, por amplificación de sondas dependiente de ligamento múltiple, muestras de médula ósea en el momento del diagnóstico de 25 adultos con LLA-B madura tratados con rituximab y quimioterapia específica. Resultados: Las CNA más frecuentes fueron las alteraciones en la región 14q32.33 (11 casos, 44%), seguidas de las alteraciones en los genes reguladores del ciclo celular CDKN2A/B y RB1 (16%). No se encontró correlación entre la presencia de estas CNA y las características clínico-biológicas o de respuesta al tratamiento. Conclusiones: La alta frecuencia de alteraciones en la región 14q32.33, CDKN2A/B y RB1 encontradas en este estudio podría explicar la agresividad e invasividad de la LLA-B madura (AU)

Background and objective: Unlike Burkitt lymphoma, molecular abnormalities other than C-MYC rearrangements have scarcely been studied in patients with mature B acute lymphoblastic leukemia (B-ALL). The aim of this study was to analyze the frequency and prognostic significance of copy number alterations (CNA) in genes involved in lymphoid differentiation, cell cycle and tumor suppression in adult patients with B-ALL. Patients and methods: We have analyzed by multiplex ligation-dependent probe amplification the genetic material from bone marrow at diagnosis from 25 adult B-ALL patients treated with rituximab and specific chemotherapy. Results: The most frequent CNA were alterations in the 14q32.33 region (11 cases, 44%) followed by alterations in the cell cycle regulator genes CDKN2A/B and RB1 (16%). No correlation between the presence of specific CNA and the clinical-biologic features or the response to therapy was found. Conclusions: The high frequency of CNA in the 14q32.33 region, CDKN2A/B and RB1 found in our study could contribute to the aggressiveness and invasiveness of mature B-ALL (AU)

SATB1 is a potential therapeutic target in intrahepatic cholangiocarcinoma

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignant tumor of the liver with a poor prognosis. Upregulation of special ATrich sequence-binding protein 1 (SATB1) promotes tumor progression. However, little is known about the role of SATB1 in ICC tumorigenesis. Methods: We firstly investigated the expression of SATB1 in 88 cases of ICC by immunohistochemistry (IHC), QRTPCR, and western blot. Meanwhile, we constructed stably knockdown (shRNA) of SATB1 in ICC cell lines to evaluate the effects of SATB1 on the ability of cell proliferation and invasion by MTT and transwell invasion assay. Results: Our result showed that SATB1 was overexpressed in ICC tissues samples. Knockdown of SATB1 could inhibit ICC cell proliferation, and suppress ICC cell invasion of ICC cell lines. In addition, the depletion of SATB1 expression suppressed the MYC levels in vitro. Conclusions: Our results highlight the significance of SATB1 in ICC and suggest that SATB1 could be a promising therapy target and a potential biomarker for prognosis in ICC patients (AU)

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Lack of correlation between DNA copy number and mRNA expression levels of c-myc in gamma-radiation-induced mouse thymic lymphomas by using quantitative real-time PCR

Background. It is well documented that over-expressionof the c-myc proto-oncogene occurs in thevast majority of mouse thymic lymphomas inducedby gamma-irradiation, evidencing the importance of thisgene in T-cell lymphomagenesis. However, it remainsunknown whether elevated levels of c-mycexpression are driven by extra c-myc copy numbers.Materials and methods. Here we use a quantitativetest on the basis of real-time PCR to determine thecellular copy number of c-myc in a set of 14 g-radiation-induced thymic lymphomas obtained from(C57BL/6J x BALB/cJ) F1 hybrid mice with increasedmRNA c-myc expression.Results. Since 5 out of 14 (35.7%) cases had no extracopy numbers of c-myc, gene amplification was obviouslynot the cause of c-myc over-expression inthese tumours. In the remaining 9 tumours, c-mycover-expression was also accompanied with extraDNA copy numbers. Therefore, c-myc amplificationmight be a consequence of the genomic instabilitysubsequent to the up-regulation of c-myc. However,linear regression analysis showed a lack of correlationbetween increasing DNA copy numbers andmRNA over expression of c-myc in these tumours (r= 0.029, p = 0.94).Conclusion. De-regulation of c-myc does not necessarilyimply amplification of this gene in these tumours.This report is, to our knowledge, the firstone comparing c-myc amplification with expressionin lymphomas of the T-cell lineage

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Gammagrafía con MIBG en el neuroblastoma: algo más que una imagen / MIBG scintigraphy in neuroblastoma: something more than an image

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Sobreexpresión de c-myc y pérdida de heterozigosidad en 2p, 3p, 5q, 17p y 18q en carcinoma colorrectal esporádico / Overexpression of c-myc and loss of heterozigosity on 2p, 3p, 5q, 17p and 18q in sporadic colorectal carcinoma

Objetivo: el objetivo del presente trabajo es evaluar la importanciapronóstica de la pérdida de heterozigosidad en las regiones2p, 3p, 5q, 17p y 18q y de la sobreexpresión del genc-myc en el carcinoma colorrectal esporádico, mediante el estudiode la supervivencia libre de enfermedad tras cirugía potencialmentecurativa.Métodos: se han analizado muestras tumorales y no tumoralesde mucosa colónica de 153 pacientes. El 51% de los pacienteseran varones y la edad media de la serie fue 67 años. Los tumoresfueron proximales en 37 casos, distales en 37 y localizados enrecto en 79. Se analizó la sobreexpresión del RNA de c-myc porNorthern blot, y la presencia de pérdida de heterozigosidad en lasdiferentes regiones consideradas por análisis de microsatélites.Resultados: se detectó sobreexpresión de c-myc en el 25%de los casos, y pérdida de heterozigosidad en alguna de las regionesestudiadas en el 48%. No hubo asociación entre las variablesclínicas o patológicas y las alteraciones génicas. Se encontró unintervalo libre de enfermedad más corto para los pacientes conpérdida de heterozigosidad y sobreexpresión de c-myc, y este factortuvo valor pronóstico independiente en el análisis multivariante(RR: 4.34, p < 0,0001).Conclusiones: la coexistencia de pérdida de heterozigosidady sobreexpresión del oncogén c-myc distingue un grupo de pacientescon recurrencia más precoz tras cirugía curativa por carcinomacolorrectal

Aim: the aim of the present study is to evaluate the prognosticinfluence of loss of heterozygosity on 2p, 3p, 5q, 17p and 18q,and c-myc overexpression on surgically treated sporadic colorectalcarcinoma.Methods: tumor and non-tumor tissue samples from 153 patientswere analyzed. Fifty-one percent of patients were male, andmean age in the series was 67 years. Tumors were located in theproximal colon in 37 cases, in the distal bowel in 37, and in therectum in 79 patients. c-myc overexpression was studied bymeans of Northern blot analysis, and loss of heterozigositythrough microsatellite analysis.Results: c-myc overexpression was detected in 25% of cases,and loss of heterozygosity in at least one of the studied regionsin 48%. There was no association between clinical andpathologic features, and genetic alterations. The disease-freeinterval was significantly shorter for patients with both geneticalterations; the presence of both events was an independentprognostic factor for poor outcome in the multivariate analysis(RR: 4.34, p < 0.0001).Conclusions: the presence of both loss of heterozygosity andoverexpression of the c-myc oncogene separates a subset of colorectalcarcinoma patients who have a shorter disease-free intervalafter curative-intent surgery