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Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid

We investigated the frequency, predictors, and evolution of acute lymphoblastic leukemia (ALL) in patients with CNS relapse and introduced a novel method for studying BCR-ABL1 protein variants in cDNA from bone marrow (BM) and cerebrospinal fluid (CSF) blast cells. A total of 128 patients were analy...

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Autores principales: Sanchez, Ricardo, Ayala, Rosa, Alonso, Rafael Alberto, Martínez, María Pilar, Ribera, Jordi, García, Olga, Sanchez-Pina, José, Mercadal, Santiago, Montesinos, Pau, Martino, Rodrigo, Barba, Pere, González-Campos, José, Barrios, Manuel, Lavilla, Esperanza, Gil, Cristina, Bernal, Teresa, Escoda, Lourdes, Abella, Eugenia, Amigo, Ma Luz, Moreno, Ma José, Bravo, Pilar, Guàrdia, Ramón, Hernández-Rivas, Jesús-María, García-Guiñón, Antoni, Piernas, Sonia, Ribera, José-María, Martínez-López, Joaquín
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486784/
https://www.ncbi.nlm.nih.gov/pubmed/28451802
http://dx.doi.org/10.1007/s00277-017-3002-1
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author Sanchez, Ricardo
Ayala, Rosa
Alonso, Rafael Alberto
Martínez, María Pilar
Ribera, Jordi
García, Olga
Sanchez-Pina, José
Mercadal, Santiago
Montesinos, Pau
Martino, Rodrigo
Barba, Pere
González-Campos, José
Barrios, Manuel
Lavilla, Esperanza
Gil, Cristina
Bernal, Teresa
Escoda, Lourdes
Abella, Eugenia
Amigo, Ma Luz
Moreno, Ma José
Bravo, Pilar
Guàrdia, Ramón
Hernández-Rivas, Jesús-María
García-Guiñón, Antoni
Piernas, Sonia
Ribera, José-María
Martínez-López, Joaquín
author_facet Sanchez, Ricardo
Ayala, Rosa
Alonso, Rafael Alberto
Martínez, María Pilar
Ribera, Jordi
García, Olga
Sanchez-Pina, José
Mercadal, Santiago
Montesinos, Pau
Martino, Rodrigo
Barba, Pere
González-Campos, José
Barrios, Manuel
Lavilla, Esperanza
Gil, Cristina
Bernal, Teresa
Escoda, Lourdes
Abella, Eugenia
Amigo, Ma Luz
Moreno, Ma José
Bravo, Pilar
Guàrdia, Ramón
Hernández-Rivas, Jesús-María
García-Guiñón, Antoni
Piernas, Sonia
Ribera, José-María
Martínez-López, Joaquín
author_sort Sanchez, Ricardo
collection PubMed
description We investigated the frequency, predictors, and evolution of acute lymphoblastic leukemia (ALL) in patients with CNS relapse and introduced a novel method for studying BCR-ABL1 protein variants in cDNA from bone marrow (BM) and cerebrospinal fluid (CSF) blast cells. A total of 128 patients were analyzed in two PETHEMA clinical trials. All achieved complete remission after imatinib treatment. Of these, 30 (23%) experienced a relapse after achieving complete remission, and 13 (10%) had an isolated CNS relapse or combined CNS and BM relapses. We compared the characteristics of patients with and without CNS relapse and further analyzed CSF and BM samples from two of the 13 patients with CNS relapse. In both patients, classical sequencing analysis of the kinase domain of BCR-ABL1 from the cDNA of CSF blasts revealed the pathogenic variant p.L387M. We also performed ultra-deep next-generation sequencing (NGS) in three samples from one of the relapsed patients. We did not find the mutation in the BM sample, but we did find it in CSF blasts with 45% of reads at the time of relapse. These data demonstrate the feasibility of detecting BCR-ABL1 mutations in CSF blasts by NGS and highlight the importance of monitoring clonal evolution over time.
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spelling pubmed-54867842017-07-11 Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid Sanchez, Ricardo Ayala, Rosa Alonso, Rafael Alberto Martínez, María Pilar Ribera, Jordi García, Olga Sanchez-Pina, José Mercadal, Santiago Montesinos, Pau Martino, Rodrigo Barba, Pere González-Campos, José Barrios, Manuel Lavilla, Esperanza Gil, Cristina Bernal, Teresa Escoda, Lourdes Abella, Eugenia Amigo, Ma Luz Moreno, Ma José Bravo, Pilar Guàrdia, Ramón Hernández-Rivas, Jesús-María García-Guiñón, Antoni Piernas, Sonia Ribera, José-María Martínez-López, Joaquín Ann Hematol Original Article We investigated the frequency, predictors, and evolution of acute lymphoblastic leukemia (ALL) in patients with CNS relapse and introduced a novel method for studying BCR-ABL1 protein variants in cDNA from bone marrow (BM) and cerebrospinal fluid (CSF) blast cells. A total of 128 patients were analyzed in two PETHEMA clinical trials. All achieved complete remission after imatinib treatment. Of these, 30 (23%) experienced a relapse after achieving complete remission, and 13 (10%) had an isolated CNS relapse or combined CNS and BM relapses. We compared the characteristics of patients with and without CNS relapse and further analyzed CSF and BM samples from two of the 13 patients with CNS relapse. In both patients, classical sequencing analysis of the kinase domain of BCR-ABL1 from the cDNA of CSF blasts revealed the pathogenic variant p.L387M. We also performed ultra-deep next-generation sequencing (NGS) in three samples from one of the relapsed patients. We did not find the mutation in the BM sample, but we did find it in CSF blasts with 45% of reads at the time of relapse. These data demonstrate the feasibility of detecting BCR-ABL1 mutations in CSF blasts by NGS and highlight the importance of monitoring clonal evolution over time. Springer Berlin Heidelberg 2017-04-27 2017 /pmc/articles/PMC5486784/ /pubmed/28451802 http://dx.doi.org/10.1007/s00277-017-3002-1 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Sanchez, Ricardo
Ayala, Rosa
Alonso, Rafael Alberto
Martínez, María Pilar
Ribera, Jordi
García, Olga
Sanchez-Pina, José
Mercadal, Santiago
Montesinos, Pau
Martino, Rodrigo
Barba, Pere
González-Campos, José
Barrios, Manuel
Lavilla, Esperanza
Gil, Cristina
Bernal, Teresa
Escoda, Lourdes
Abella, Eugenia
Amigo, Ma Luz
Moreno, Ma José
Bravo, Pilar
Guàrdia, Ramón
Hernández-Rivas, Jesús-María
García-Guiñón, Antoni
Piernas, Sonia
Ribera, José-María
Martínez-López, Joaquín
Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid
title Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid
title_full Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid
title_fullStr Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid
title_full_unstemmed Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid
title_short Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid
title_sort clinical characteristics of patients with central nervous system relapse in bcr-abl1-positive acute lymphoblastic leukemia: the importance of characterizing abl1 mutations in cerebrospinal fluid
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486784/
https://www.ncbi.nlm.nih.gov/pubmed/28451802
http://dx.doi.org/10.1007/s00277-017-3002-1
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