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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.
Authors: 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
Keywords: Acute lymphoblastic leukemia relapse;BCR-ABL1;Central nervous system;Mutation analysis;Neoplasia
metadata.dc.subject.mesh: Adult
Aged, 80 and over
Central Nervous System
Feasibility Studies
Fusion Proteins, bcr-abl
High-Throughput Nucleotide Sequencing
Kaplan-Meier Estimate
Middle Aged
Models, Molecular
Outcome Assessment, Health Care
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Protein Structure, Tertiary
Proto-Oncogene Proteins c-abl
Issue Date: 27-Apr-2017
Abstract: 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.
metadata.dc.identifier.doi: 10.1007/s00277-017-3002-1
Appears in Collections:Producción 2020

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