Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/2672
Título : 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
Autor : 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
Filiación: [Sanchez,R; Ayala,R; Alonso,RA; Martínez,MP, Sanchez-Pina; Martínez-López,J] Instituto de Investigación Hospital 12 de Octubre (i+12), Servicio de Hematología, Hematología Traslacional, Hospital Universitario 12 de Octubre, Spain. [Ribera,J; García,O; Ribera,JM] Institut de Recerca contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Badalona, Spain. [Mercadal,S] ICO-Hospital Duran i Reynals (Bellvitge), Barcelona, Spain. [Montesinos,P] Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Martino,R] Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Barba,P] Hospital Universitari Vall d’Hebron, Barcelona, Spain. [González-Campos,J] Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Barrios,M] Hospital Regional Universitario Carlos Haya, Málaga, Spain. [Lavilla,E] Hospital Universitario Lucus Augusti, Lugo, Spain. [Gil,C] Hospital General Universitario de Alicante, Alicante, Spain. [Bernal,T] Hospital Universitario Central de Asturias, Oviedo, Spain. [Escoda,L] Hospital Universitari Joan XXIII, Tarragona, Spain. [Abella,E] Hospital del Mar, Barcelona, Spain. [Amigo,ML] Hospital General Universitario Morales Meseguer, Murcia, Spain. [Moreno,MJ] Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Bravo,P] Hospital de Fuenlabrada, Fuenlabrada, Madrid, Spain. [Guàrdia,R] ICO-Hospital Universitari Dr. Josep Trueta, Girona, Spain. [Hernández-Rivas,JM] Hospital Universitario de Salamanca, Salamanca, Spain. [García-Guiñón,A] Hospital Universitari Arnau de Vilanova, Lleida, Spain. [Piernas,S] Hospital Universitari Parc Taulí, Sabadell, Barcelona, Spain.
Palabras clave : Neoplasia
Acute lymphoblastic leukemia relapse
Central nervous system
Mutation analysis
Humanos
Mesilato de imatinib
Mutación
Leucemia-Linfoma linfoblástico de células precursoras
Proteínas proto-oncogénicas c-bcr
Recurrencia
Médula ósea
Evolución clonal
ADN complementario
Secuenciación de nucleótidos de alto rendimiento
BCR-ABL1
MeSH: Medical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Bone Marrow
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Clonal Evolution
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA::DNA, Single-Stranded::DNA, Complementary
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide Sequencing
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Benzamides::Imatinib Mesylate
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Lymphoid::Precursor Cell Lymphoblastic Leukemia-Lymphoma
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Oncogene Proteins::Proto-Oncogene Proteins::Proto-Oncogene Proteins c-bcr
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence
Fecha de publicación : 27-Apr-2017
Editorial : Springer Verlag
Cita Bibliográfica: Sanchez R, Ayala R, Alonso RA, Marínez MP, Ribera J, García O, et al. 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. Ann Hematol. 2017 Apr 27.
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.
URI: http://hdl.handle.net/10668/2672
Versión del editor : https://link.springer.com/article/10.1007%2Fs00277-017-3002-1
DOI: 10.1007/s00277-017-3002-1
ISSN : 0939-5555 (Print)
1432-0584 (Online)
Appears in Collections:01- Artículos - Hospital Virgen de la Victoria
01- Artículos - Hospital Virgen del Rocío
01- Artículos - Hospital Regional de Málaga

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