المؤلفون: Pascual Izquierdo, Cristina, Mingot Castellano, María Eva, Kerguelen Fuentes, Ana E., García-Arroba Peinado, José, Cid, Joan, Moraima Jimenez, Maria, Valcarcel, David, Gómez Seguí, Inés, de la Rubia, Javier, Martin, Paz, Goterris, Rosa, Hernández, Luis, Tallón, Inmaculada, Varea, Sara, Fernández, Marta, García Muñoz, Nadia, Vara, Míriam, Fernández Zarzoso, Miguel, García Candel, Faustino, Paciello, María Liz, García García, Irene, Zalba, Saioa, Campuzano, Verónica, Gala, José María, Vidán Estévez, Julia, Moreno Jiménez, Gemma, López Lorenzo, José Luis, González Arias, Elena, Freiría, Carmen, Solé, María, Ávila Idrovo, Laura Francisca, Hernández Castellet, José Carlos, Cruz, Naylen, Lavilla, Esperanza, Pérez Montaña, Albert, Atucha, Jon Ander, Moreno Beltrán, María Esperanza, Moreno Macías, Juán Ramón, Salinas, Ramón, del Rio Garma, Julio

المصدر: Blood Advances. Vol. 6, nº 24, December 2022, pp. 6219 - 6227

مصطلحات موضوعية: caplacizumab, prednisone, rituximab

الوصف: Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX. ; 9 páginas

وصف الملف: application/pdf

العلاقة: http://hdl.handle.net/10498/29789Test

الإتاحة: https://doi.org/10.1182/bloodadvances.2022008028Test
http://hdl.handle.net/10498/29789Test

المؤلفون: Rubia, Javier DE LA, Gómez-Seguí, Inés, Cid, Joan, Valcárcel, David, Goterris, Rosa, Zarzoso, Miguel Fernández, Mingot-Castellano, María Eva, Izquierdo, Cristina Pascual, Hernández, Ana Oliva, Nieto, Jorge Martínez, Idrovo, Laura F. Ávila, Coronel, María Liz Paciello, Hernández, Luis M.

المصدر: HemaSphere ; volume 7, issue S3, page e61163bd ; ISSN 2572-9241

الإتاحة: https://doi.org/10.1097/01.hs9.0000973312.61163.bdTest

المؤلفون: Chorão, Pedro, Montoro, Juan, Balaguer-Roselló, Aitana, Guerreiro, Manuel, Villalba, Marta, Facal, Ana, Solves, Pilar, Gómez-Segui, Inés, Pasquini, Marcelo C., Granados, Pablo, Bataller, Ana, Louro, Alberto, de la Rubia, Javier, Sanz, Miguel A., Sanz, Jaime

المصدر: Transplantation and Cellular Therapy ; volume 29, issue 5, page 322.e1-322.e5 ; ISSN 2666-6367

مصطلحات موضوعية: Transplantation, Cell Biology, Hematology, Molecular Medicine, Immunology and Allergy

الإتاحة: https://doi.org/10.1016/j.jtct.2023.01.016Test
https://api.elsevier.com/content/article/PII:S2666636723000374?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666636723000374?httpAccept=text/plainTest

المؤلفون: Pascual Izquierdo, Cristina, Mingot Castellano, María Eva, Kerguelen Fuentes, Ana E., García Arroba Peinado, José, Cid Vidal, Joan, Jimenez, Maria Moraima, Valcarcel, David, Gómez Seguí, Inés, Rubia, Javier de la, Martin, Paz, Goterris, Rosa, Hernández, Luis, Tallón, Inmaculada, Varea, Sara, Fernández, Marta, García Muñoz, Nadia, Vara, Míriam, Fernández Zarzoso, Miguel, García Candel, Faustino, Paciello, María Liz, García García, Irene, Zalba, Saioa, Campuzano, Verónica, Gala, José María, Vidán Estévez, Julia, Moreno Jiménez, Gemma, López Lorenzo, José Luis, González Arias, Elena, Freiría, Carmen, Solé, María, Ávila Idrovo, Laura Francisca, Hernández Castellet, José Carlos, Cruz, Naylen, Lavilla, Esperanza, Pérez Montaña, Albert, Atucha, Jon Ander, Moreno Beltrán, María Esperanza, Moreno Macías, Juán Ramón, Salinas, Ramón, Rio Garma, Julio del, Spanish Apheresis Group (GEA), Spanish Thrombotic Thrombocytopenic Purpura Registry (REPTT)

المصدر: Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

مصطلحات موضوعية: Rituximab, Trombosi, Assaigs clínics, Thrombosis, Clinical trials

الوصف: Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX.

وصف الملف: 9 p.; application/pdf

العلاقة: Reproducció del document publicat a: https://doi.org/10.1182/bloodadvances.2022008028Test; Blood Advances, 2022, vol. 6, num. 24, p. 6219-6227; https://doi.org/10.1182/bloodadvances.2022008028Test; http://hdl.handle.net/2445/196688Test

الإتاحة: https://doi.org/10.1182/bloodadvances.2022008028Test
http://hdl.handle.net/2445/196688Test

المؤلفون: Gómez Seguí, Inés

مرشدي الرسالة: Sanz Alonso, Miguel Ángel, Such Taboada, Esperanza, Departament de Medicina

مصطلحات موضوعية: leucemia, citogenética, IKZF1, microdeleciones, UNESCO::CIENCIAS MÉDICAS ::Medicina interna::Hematología

الوصف: La leucemia Linfoblástica Aguda (LLA) es una neoplasia caracterizada por una gran diversidad de alteraciones genéticas. En los últimos años, se ha descrito la ocurrencia de pequeñas deleciones focales en genes de relevancia para la célula linfoide. En concreto, las que afectan a IKZF1 parecen tener valor pronóstico en la edad pediátrica. OBJETIVOS: Estudiar la presencia de microdeleciones en los genes CDKN2A, CDKN2B, PAX5, ETV6, EBF1, BTG1, RB1, la región pseudoautosómica del cromosoma X/Y (PAR1) en una serie de pacientes con LLA. Además, estudiar la presencia de mutaciones, microdeleciones y alteración del patrón de expresión de isoformas del gen IKZF1 en estos pacientes. MÉTODOS: Se reunió una serie de 342 pacientes (164 niños y 178 adultos) de 0 a 85 años. El 85% mostró fenotipo B y el resto T. El estudio de microdeleciones se realizó mediante MLPA (MRC Holland) con el kit P0335 que incluyó sondas para todos los genes de interés. El estudio de mutaciones se realizó en todos los exones codificantes del gen IKZF1 mediante técnica de cribado por High Resolution Melting y posterior confirmación con secuenciación tipo Sanger. El estudio del patrón de isoformas se realizó mediante RT-PCR y lectura en gel de agarosa. RESULTADOS: Hallamos alteraciones del gen IKZF1 en el 26% de los pacientes. Sólo se hallaron en la LLA de estirpe B, su frecuencia aumentó progresivamente con la edad y ocurrieron con mayor frecuencia en la LLA-Ph positiva (71%) que en el resto (20%). Casi la totalidad (97%) de las alteraciones de IKZF1 fueron microdeleciones intragénicas, siendo mutaciones las restantes alteraciones encontradas. La microdeleción más frecuente fue la que afectó a los exones del 4 al 7, resultando en la expresión de la isoforma patológica Ik6. En el resto de casos con microdeleciones observamos ausencia completa de expresión o un patrón normal de isoformas. Las microdeleciones intragénicas se hallaron con igual frecuencia en la LLA-B (63%) y la LLA-T (62%), tanto pediátricas (62%) como de adulto (63%). Los genes más frecuentemente involucrados fueron CDKN2A (30%), CDKN2B (28%), PAX5 (18%) y ETV6 (10%), que se hallan de manera concomitante en muchos de los casos. Las deleciones de CDKN2A y CDKN2B fueron más frecuentes en las LLA-T, mientras que en las de BTG1 y EBF1 ocurrieron exclusivamente en las LLA-B. En los pacientes pediátricos, la estratificación de riesgo citogenético fue el factor que más influyó en la supervivencia y en la probabilidad de recaída. En los pacientes adultos, las microdeleciones de CDKN2A/B y las de ETV6 mostraron tener valor pronóstico independiente para la supervivencia global, mientras que para la probabilidad de recaída lo han sido las deleciones de ETV6 y la concurrencia de ≥ 4 deleciones. Las alteraciones de IKZF1 se han asociado a un pronóstico adverso, si bien los tratamientos aplicados adaptados al riesgo de recaída pueden haber condicionado la ausencia de significación estadística en el análisis multivariante. CONCLUSIONES: Las alteraciones de IKZF1 y las microdeleciones intragénicas son eventos frecuentes en la LLA. Algunas de ellas han demostrado tener valor pronóstico en nuestra serie.

الوصف (مترجم): Acute Lymphoblastic Leukemia (ALL) is a neoplasm characterized by a great diversity of genetic abnormalities. Recently, it has been described the occurrence of small focal microdeletions involving important genes for the leukemic cell. IKZF1 deletions seem to be of special interest due to the prognostic value shown in pediatric series. AIMS: To study the presence of microdeletions in the CDKN2A, CDKN2B, PAX5, ETV6, EBF1, BTG1, RB1 genes and the pseudoatosomic region of X/Y (PAR1) in a series of patients diagnosed with ALL. To study the presence of mutations, microdeletions and expression of different isoforms of the IKZF1 gene in that series. MÉTODOS: A total of 342 patients diagnosed with ALL was included in this study (164 children y 178 adults) from 0 to 85 years of age. Eighty-five percent of patients showed B-ALL and 15% T-ALL. Microdeletions were studied by MLPA (MRC Holland) with P0335 kit, which includes several probes for the selected genes. Mutational studies were performed in all coding exons of the IKZF1 gene using High Resolution Melting technique as screening and Sanger sequencing for confirmation. Isoform pattern was studied by RT-PCR and amplified products were visualized in agarose gel. RESULTADOS: IKZF1 gene abnormalities were seen in 26% of patients. They were only seen in B-ALL cases, its frequency increased with age and were more frequently found in Philadelphia positive ALL (71%) than in other ALL cases (20%). Almost all abnormalities were microdeletions (97%), and the remaining abnormalities were mutations. The most frequent microdeletion was the one that involved exons 4 to 7, leading to the expression of the aberrant short isoform Ik6. The remaining cases showed a normal expression pattern of isoforms or lack of expression. Gene microdeletions were seen with the same frequency in B-ALL (63%) as in T-ALL (62%) and in children (62%) as in adults (63%). The most frequently involved genes were CDKN2A (30%), CDKN2B (28%), PAX5 (18%) and ETV6 (10%), which were concurrently deleted in several cases. Deletions in CDKN2A y CDKN2B were more frequent in T-ALL, while BTG1 and EBF1 were found exclusively in B-ALL. In pediatric patients, cytogenetic risk stratification was the only independent variable conditioning survival and relapse in multivariate analyses. In adult patients, CDKN2A/B and ETV6 deletions showed an independent prognostic value for overall survival, and ETV6 deletions and the concurrence of ≥ 4 deletions for relapse-free survival. IKZF1 deletions confered a worse prognosis, however, this association was not independent in multivariate analyses, maybe due to the risk-stratified treatment protocols used in this series. CONCLUSIONS: IKZF1 gene abnormalities and gene microdeletions are frequent events in ALL. Some of them have shown prognostic value in our series.

الوصول الحر: http://hdl.handle.net/10550/50737Test

المؤلفون: Gómez Seguí, Inés

مرشدي الرسالة: Sanz Alonso, Miguel Ángel, Such Taboada, Esperanza, Departament de Medicina

مصطلحات موضوعية: leucemia, citogenética, IKZF1, microdeleciones, UNESCO::CIENCIAS MÉDICAS ::Medicina interna::Hematología

الوصف: La leucemia Linfoblástica Aguda (LLA) es una neoplasia caracterizada por una gran diversidad de alteraciones genéticas. En los últimos años, se ha descrito la ocurrencia de pequeñas deleciones focales en genes de relevancia para la célula linfoide. En concreto, las que afectan a IKZF1 parecen tener valor pronóstico en la edad pediátrica. OBJETIVOS: Estudiar la presencia de microdeleciones en los genes CDKN2A, CDKN2B, PAX5, ETV6, EBF1, BTG1, RB1, la región pseudoautosómica del cromosoma X/Y (PAR1) en una serie de pacientes con LLA. Además, estudiar la presencia de mutaciones, microdeleciones y alteración del patrón de expresión de isoformas del gen IKZF1 en estos pacientes. MÉTODOS: Se reunió una serie de 342 pacientes (164 niños y 178 adultos) de 0 a 85 años. El 85% mostró fenotipo B y el resto T. El estudio de microdeleciones se realizó mediante MLPA (MRC Holland) con el kit P0335 que incluyó sondas para todos los genes de interés. El estudio de mutaciones se realizó en todos los exones codificantes del gen IKZF1 mediante técnica de cribado por High Resolution Melting y posterior confirmación con secuenciación tipo Sanger. El estudio del patrón de isoformas se realizó mediante RT-PCR y lectura en gel de agarosa. RESULTADOS: Hallamos alteraciones del gen IKZF1 en el 26% de los pacientes. Sólo se hallaron en la LLA de estirpe B, su frecuencia aumentó progresivamente con la edad y ocurrieron con mayor frecuencia en la LLA-Ph positiva (71%) que en el resto (20%). Casi la totalidad (97%) de las alteraciones de IKZF1 fueron microdeleciones intragénicas, siendo mutaciones las restantes alteraciones encontradas. La microdeleción más frecuente fue la que afectó a los exones del 4 al 7, resultando en la expresión de la isoforma patológica Ik6. En el resto de casos con microdeleciones observamos ausencia completa de expresión o un patrón normal de isoformas. Las microdeleciones intragénicas se hallaron con igual frecuencia en la LLA-B (63%) y la LLA-T (62%), tanto pediátricas (62%) como de adulto (63%). Los genes más frecuentemente involucrados fueron CDKN2A (30%), CDKN2B (28%), PAX5 (18%) y ETV6 (10%), que se hallan de manera concomitante en muchos de los casos. Las deleciones de CDKN2A y CDKN2B fueron más frecuentes en las LLA-T, mientras que en las de BTG1 y EBF1 ocurrieron exclusivamente en las LLA-B. En los pacientes pediátricos, la estratificación de riesgo citogenético fue el factor que más influyó en la supervivencia y en la probabilidad de recaída. En los pacientes adultos, las microdeleciones de CDKN2A/B y las de ETV6 mostraron tener valor pronóstico independiente para la supervivencia global, mientras que para la probabilidad de recaída lo han sido las deleciones de ETV6 y la concurrencia de ≥ 4 deleciones. Las alteraciones de IKZF1 se han asociado a un pronóstico adverso, si bien los tratamientos aplicados adaptados al riesgo de recaída pueden haber condicionado la ausencia de significación estadística en el análisis multivariante. CONCLUSIONES: Las alteraciones de IKZF1 y las microdeleciones intragénicas son eventos frecuentes en la LLA. Algunas de ellas han demostrado tener valor pronóstico en nuestra serie.

الوصف (مترجم): Acute Lymphoblastic Leukemia (ALL) is a neoplasm characterized by a great diversity of genetic abnormalities. Recently, it has been described the occurrence of small focal microdeletions involving important genes for the leukemic cell. IKZF1 deletions seem to be of special interest due to the prognostic value shown in pediatric series. AIMS: To study the presence of microdeletions in the CDKN2A, CDKN2B, PAX5, ETV6, EBF1, BTG1, RB1 genes and the pseudoatosomic region of X/Y (PAR1) in a series of patients diagnosed with ALL. To study the presence of mutations, microdeletions and expression of different isoforms of the IKZF1 gene in that series. MÉTODOS: A total of 342 patients diagnosed with ALL was included in this study (164 children y 178 adults) from 0 to 85 years of age. Eighty-five percent of patients showed B-ALL and 15% T-ALL. Microdeletions were studied by MLPA (MRC Holland) with P0335 kit, which includes several probes for the selected genes. Mutational studies were performed in all coding exons of the IKZF1 gene using High Resolution Melting technique as screening and Sanger sequencing for confirmation. Isoform pattern was studied by RT-PCR and amplified products were visualized in agarose gel. RESULTADOS: IKZF1 gene abnormalities were seen in 26% of patients. They were only seen in B-ALL cases, its frequency increased with age and were more frequently found in Philadelphia positive ALL (71%) than in other ALL cases (20%). Almost all abnormalities were microdeletions (97%), and the remaining abnormalities were mutations. The most frequent microdeletion was the one that involved exons 4 to 7, leading to the expression of the aberrant short isoform Ik6. The remaining cases showed a normal expression pattern of isoforms or lack of expression. Gene microdeletions were seen with the same frequency in B-ALL (63%) as in T-ALL (62%) and in children (62%) as in adults (63%). The most frequently involved genes were CDKN2A (30%), CDKN2B (28%), PAX5 (18%) and ETV6 (10%), which were concurrently deleted in several cases. Deletions in CDKN2A y CDKN2B were more frequent in T-ALL, while BTG1 and EBF1 were found exclusively in B-ALL. In pediatric patients, cytogenetic risk stratification was the only independent variable conditioning survival and relapse in multivariate analyses. In adult patients, CDKN2A/B and ETV6 deletions showed an independent prognostic value for overall survival, and ETV6 deletions and the concurrence of ≥ 4 deletions for relapse-free survival. IKZF1 deletions confered a worse prognosis, however, this association was not independent in multivariate analyses, maybe due to the risk-stratified treatment protocols used in this series. CONCLUSIONS: IKZF1 gene abnormalities and gene microdeletions are frequent events in ALL. Some of them have shown prognostic value in our series.

الوصول الحر: http://hdl.handle.net/10803/570650Test

المؤلفون: Gómez Seguí, Inés

مرشدي الرسالة: Sanz Alonso, Miguel Ángel, Such Taboada, Esperanza, Departament de Medicina

مصطلحات موضوعية: leucemia, citogenética, IKZF1, microdeleciones, UNESCO::CIENCIAS MÉDICAS ::Medicina interna::Hematología

الوصف: La leucemia Linfoblástica Aguda (LLA) es una neoplasia caracterizada por una gran diversidad de alteraciones genéticas. En los últimos años, se ha descrito la ocurrencia de pequeñas deleciones focales en genes de relevancia para la célula linfoide. En concreto, las que afectan a IKZF1 parecen tener valor pronóstico en la edad pediátrica. OBJETIVOS: Estudiar la presencia de microdeleciones en los genes CDKN2A, CDKN2B, PAX5, ETV6, EBF1, BTG1, RB1, la región pseudoautosómica del cromosoma X/Y (PAR1) en una serie de pacientes con LLA. Además, estudiar la presencia de mutaciones, microdeleciones y alteración del patrón de expresión de isoformas del gen IKZF1 en estos pacientes. MÉTODOS: Se reunió una serie de 342 pacientes (164 niños y 178 adultos) de 0 a 85 años. El 85% mostró fenotipo B y el resto T. El estudio de microdeleciones se realizó mediante MLPA (MRC Holland) con el kit P0335 que incluyó sondas para todos los genes de interés. El estudio de mutaciones se realizó en todos los exones codificantes del gen IKZF1 mediante técnica de cribado por High Resolution Melting y posterior confirmación con secuenciación tipo Sanger. El estudio del patrón de isoformas se realizó mediante RT-PCR y lectura en gel de agarosa. RESULTADOS: Hallamos alteraciones del gen IKZF1 en el 26% de los pacientes. Sólo se hallaron en la LLA de estirpe B, su frecuencia aumentó progresivamente con la edad y ocurrieron con mayor frecuencia en la LLA-Ph positiva (71%) que en el resto (20%). Casi la totalidad (97%) de las alteraciones de IKZF1 fueron microdeleciones intragénicas, siendo mutaciones las restantes alteraciones encontradas. La microdeleción más frecuente fue la que afectó a los exones del 4 al 7, resultando en la expresión de la isoforma patológica Ik6. En el resto de casos con microdeleciones observamos ausencia completa de expresión o un patrón normal de isoformas. Las microdeleciones intragénicas se hallaron con igual frecuencia en la LLA-B (63%) y la LLA-T (62%), tanto pediátricas (62%) como de adulto (63%). Los genes más frecuentemente involucrados fueron CDKN2A (30%), CDKN2B (28%), PAX5 (18%) y ETV6 (10%), que se hallan de manera concomitante en muchos de los casos. Las deleciones de CDKN2A y CDKN2B fueron más frecuentes en las LLA-T, mientras que en las de BTG1 y EBF1 ocurrieron exclusivamente en las LLA-B. En los pacientes pediátricos, la estratificación de riesgo citogenético fue el factor que más influyó en la supervivencia y en la probabilidad de recaída. En los pacientes adultos, las microdeleciones de CDKN2A/B y las de ETV6 mostraron tener valor pronóstico independiente para la supervivencia global, mientras que para la probabilidad de recaída lo han sido las deleciones de ETV6 y la concurrencia de ≥ 4 deleciones. Las alteraciones de IKZF1 se han asociado a un pronóstico adverso, si bien los tratamientos aplicados adaptados al riesgo de recaída pueden haber condicionado la ausencia de significación estadística en el análisis multivariante. CONCLUSIONES: Las alteraciones de IKZF1 y las microdeleciones intragénicas son eventos frecuentes en la LLA. Algunas de ellas han demostrado tener valor pronóstico en nuestra serie.

الوصف (مترجم): Acute Lymphoblastic Leukemia (ALL) is a neoplasm characterized by a great diversity of genetic abnormalities. Recently, it has been described the occurrence of small focal microdeletions involving important genes for the leukemic cell. IKZF1 deletions seem to be of special interest due to the prognostic value shown in pediatric series. AIMS: To study the presence of microdeletions in the CDKN2A, CDKN2B, PAX5, ETV6, EBF1, BTG1, RB1 genes and the pseudoatosomic region of X/Y (PAR1) in a series of patients diagnosed with ALL. To study the presence of mutations, microdeletions and expression of different isoforms of the IKZF1 gene in that series. MÉTODOS: A total of 342 patients diagnosed with ALL was included in this study (164 children y 178 adults) from 0 to 85 years of age. Eighty-five percent of patients showed B-ALL and 15% T-ALL. Microdeletions were studied by MLPA (MRC Holland) with P0335 kit, which includes several probes for the selected genes. Mutational studies were performed in all coding exons of the IKZF1 gene using High Resolution Melting technique as screening and Sanger sequencing for confirmation. Isoform pattern was studied by RT-PCR and amplified products were visualized in agarose gel. RESULTADOS: IKZF1 gene abnormalities were seen in 26% of patients. They were only seen in B-ALL cases, its frequency increased with age and were more frequently found in Philadelphia positive ALL (71%) than in other ALL cases (20%). Almost all abnormalities were microdeletions (97%), and the remaining abnormalities were mutations. The most frequent microdeletion was the one that involved exons 4 to 7, leading to the expression of the aberrant short isoform Ik6. The remaining cases showed a normal expression pattern of isoforms or lack of expression. Gene microdeletions were seen with the same frequency in B-ALL (63%) as in T-ALL (62%) and in children (62%) as in adults (63%). The most frequently involved genes were CDKN2A (30%), CDKN2B (28%), PAX5 (18%) and ETV6 (10%), which were concurrently deleted in several cases. Deletions in CDKN2A y CDKN2B were more frequent in T-ALL, while BTG1 and EBF1 were found exclusively in B-ALL. In pediatric patients, cytogenetic risk stratification was the only independent variable conditioning survival and relapse in multivariate analyses. In adult patients, CDKN2A/B and ETV6 deletions showed an independent prognostic value for overall survival, and ETV6 deletions and the concurrence of ≥ 4 deletions for relapse-free survival. IKZF1 deletions confered a worse prognosis, however, this association was not independent in multivariate analyses, maybe due to the risk-stratified treatment protocols used in this series. CONCLUSIONS: IKZF1 gene abnormalities and gene microdeletions are frequent events in ALL. Some of them have shown prognostic value in our series.

الوصول الحر: http://hdl.handle.net/10550/50737Test

المؤلفون: Lin, Wei Yu, Fordham, Sarah E., Hungate, Eric, Sunter, Nicola J., Elstob, Claire, Xu, Yaobo, Park, Catherine, Quante, Anne, Strauch, Konstantin, Gieger, Christian, Skol, Andrew, Rahman, Thahira, Sucheston-Campbell, Lara, Wang, Junke, Hahn, Theresa, Clay-Gilmour, Alyssa I., Jones, Gail L., Marr, Helen J., Jackson, Graham H., Menne, Tobias, Collin, Mathew, Ivey, Adam, Hills, Robert K., Burnett, Alan K., Russell, Nigel H., Fitzgibbon, Jude, Larson, Richard A., Le Beau, Michelle M., Stock, Wendy, Heidenreich, Olaf, Alharbi, Abrar, Allsup, David J., Houlston, Richard S., Norden, Jean, Dickinson, Anne M., Douglas, Elisabeth, Lendrem, Clare, Daly, Ann K., Palm, Louise, Piechocki, Kim, Jeffries, Sally, Bornhäuser, Martin, Röllig, Christoph, Altmann, Heidi, Ruhnke, Leo, Kunadt, Desiree, Wagenführ, Lisa, Cordell, Heather J., Darlay, Rebecca, Andersen, Mette K., Fontana, Maria C., Martinelli, Giovanni, Marconi, Giovani, Sanz, Miguel A., Cervera, José, Gómez-Seguí, Inés, Cluzeau, Thomas, Moreilhon, Chimène, Raynaud, Sophie, Sill, Heinz, Voso, Maria Teresa, Lo-Coco, Francesco, Dombret, Hervé, Cheok, Meyling, Preudhomme, Claude, Gale, Rosemary E., Linch, David, Gaal-Wesinger, Julia, Masszi, Andras, Nowak, Daniel, Hofmann, Wolf Karsten, Gilkes, Amanda, Porkka, Kimmo, Milosevic Feenstra, Jelena D., Kralovics, Robert, Grimwade, David, Meggendorfer, Manja, Haferlach, Torsten, Krizsán, Szilvia, Bödör, Csaba, Stölzel, Friedrich, Onel, Kenan, Allan, James M.

مصطلحات موضوعية: Acute myeloid leukaemia, Cancer genomics, Risk factors

الوصف: Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10−8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10−10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).

العلاقة: https://hull-repository.worktribe.com/output/3865990Test; Nature Communications; Volume 12; Issue 1; https://hull-repository.worktribe.com/file/3865990/1/Published%20articleTest

الإتاحة: https://doi.org/10.1038/s41467-021-26551-xTest
https://hull-repository.worktribe.com/file/3865990/1/Published%20articleTest
https://hull-repository.worktribe.com/output/3865990Test

المؤلفون: Lin, Wei-Yu, Fordham, Sarah E., Hungate, Eric, Sunter, Nicola J., Elstob, Claire, Xu, Yaobo, Park, Catherine, Quante, Anne, Strauch, Konstantin, Gieger, Christian, Skol, Andrew, Rahman, Thahira, Sucheston-Campbell, Lara, Wang, Junke, Hahn, Theresa, Clay-Gilmour, Alyssa I., Jones, Gail L., Marr, Helen J., Jackson, Graham H., Menne, Tobias, Collin, Mathew, Ivey, Adam, Hills, Robert K., Burnett, Alan K., Russell, Nigel H., Fitzgibbon, Jude, Larson, Richard A., Le Beau, Michelle M., Stock, Wendy, Heidenreich, Olaf, Alharbi, Abrar, Allsup, David J., Houlston, Richard S., Norden, Jean, Dickinson, Anne M., Douglas, Elisabeth, Lendrem, Clare, Daly, Ann K., Palm, Louise, Piechocki, Kim, Jeffries, Sally, Bornhäuser, Martin, Röllig, Christoph, Altmann, Heidi, Ruhnke, Leo, Kunadt, Desiree, Wagenführ, Lisa, Cordell, Heather J., Darlay, Rebecca, Andersen, Mette K., Fontana, Maria C., Martinelli, Giovanni, Marconi, Giovanni, Sanz, Miguel A., Cervera, José, Gómez-Seguí, Inés, Cluzeau, Thomas, Moreilhon, Chimène, Raynaud, Sophie, Sill, Heinz, Voso, Maria Teresa, Lo-Coco, Francesco, Dombret, Hervé, Cheok, Meyling, Preudhomme, Claude, Gale, Rosemary E., Linch, David, Gaal-Wesinger, Julia, Masszi, Andras, Nowak, Daniel, Hofmann, Wolf-Karsten, Gilkes, Amanda, Porkka, Kimmo, Milosevic Feenstra, Jelena D., Kralovics, Robert, Grimwade, David, Meggendorfer, Manja, Haferlach, Torsten, Krizsán, Szilvia, Bödör, Csaba, Stölzel, Friedrich, Onel, Kenan, Allan, James M.

الوصف: Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10−8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10−10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).

وصف الملف: text

العلاقة: http://eprints.gla.ac.uk/257986/2/257986.pdfTest; Lin, W.-Y. et al. (2021) Genome-wide association study identifies susceptibility loci for acute myeloid leukemia. Nature Communications , 12, 6233. (doi:10.1038/s41467-021-26551-x ) (PMID:34716350)

الإتاحة: https://doi.org/10.1038/s41467-021-26551-xTest
http://eprints.gla.ac.uk/257986Test/
http://eprints.gla.ac.uk/257986/2/257986.pdfTest

المؤلفون: Liquori, Alessandro, Lesende, Iván, Palomo Sanchís, Laura, Avetisyan, Gayane, Ibáñez, Mariam, González-Romero, Elisa, Boluda-Navarro, Mireia, Morote-Faubel, Mireya, Garcia-Ruiz, Cristian, Martinez-Valiente, Cristina, Santiago-Balsera, Marta, Gomez-Seguí, Inés, Sanjuan-Pla, Alejandra, Sanz, Miguel A., Sanz, Guillermo, Sole, F., Such, Esperanza, Cervera, José, Universitat Autònoma de Barcelona

مصطلحات موضوعية: Myelodysplastic syndromes, Cytogenetics, Next-generation sequencing, Myeloid neoplasm, SNP array, Karyotype

الوصف: Chromosomal abnormalities and somatic mutations are found in patients with myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in around 50-80% of cases. The identification of these alterations is important for the accurate diagnosis and prognostic classification of these patients. Often, an apparently normal or failed karyotype might lead to an inadequate estimation of the prognostic risk, and several strategies should be combined to solve these cases. The aim of this study was to introduce a novel next-generation sequencing (NGS)-based strategy for the simultaneous detection of all the clinically relevant genetic alterations associated with these disorders. We validated this approach on a large cohort of patients by comparing our findings with those obtained with standard-of-care methods (i.e., karyotype and SNP-arrays). We show that our platform represents a significant improvement on current strategies in defining diagnosis and risk stratification of patients with MDS and myeloid-related disorders. Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms are clonal disorders that share most of their cytogenetic and molecular alterations. Despite the increased knowledge of the prognostic importance of genetics in these malignancies, next-generation sequencing (NGS) has not been incorporated into clinical practice in a validated manner, and the conventional karyotype remains mandatory in the evaluation of suspected cases. However, non-informative cytogenetics might lead to an inadequate estimation of the prognostic risk. Here, we present a novel targeted NGS-based assay for the simultaneous detection of all the clinically relevant genetic alterations associated with these disorders. We validated this platform in a large cohort of patients by performing a one-to-one comparison with the lesions from karyotype and single-nucleotide polymorphism (SNP) arrays. Our strategy demonstrated an approximately 97% concordance with standard clinical assays, ...

وصف الملف: application/pdf

العلاقة: Ministerio de Economía y Competitividad PI16/01113; Ministerio de Economía y Competitividad PI16/00665; Instituto de Salud Carlos III PI17/0575; Instituto de Salud Carlos III PI18/1472; Instituto de Salud Carlos III PI19/00812; Ministerio de Educación, Cultura y Deporte GV/2019/084; Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR288; Cancers; Vol. 13 (april 2021); https://ddd.uab.cat/record/255507Test; urn:10.3390/cancers13081947; urn:oai:ddd.uab.cat:255507; urn:pmcid:PMC8072643; urn:pmc-uid:8072643; urn:oai:pubmedcentral.nih.gov:8072643; urn:pmid:33919541

الإتاحة: https://ddd.uab.cat/record/255507Test