Sanchez, RicardoAyala, RosaAlonso, Rafael AlbertoMartínez, María PilarRibera, JordiGarcía, OlgaSanchez-Pina, JoséMercadal, SantiagoMontesinos, PauMartino, RodrigoBarba, PereGonzález-Campos, JoséBarrios, ManuelLavilla, EsperanzaGil, CristinaBernal, TeresaEscoda, LourdesAbella, EugeniaAmigo, Ma LuzMoreno, Ma JoséBravo, PilarGuàrdia, RamónHernández-Rivas, Jesús-MaríaGarcía-Guiñón, AntoniPiernas, SoniaRibera, José-MaríaMartínez-López, Joaquín2017-05-262017-05-262017-04-27Sanchez 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 27.0939-5555http://hdl.handle.net/10668/2672We 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.enNeoplasiaAcute lymphoblastic leukemia relapseCentral nervous systemMutation analysisHumanosMesilato de imatinibMutaciónLeucemia-Linfoma linfoblástico de células precursorasProteínas proto-oncogénicas c-bcrRecurrenciaMédula óseaEvolución clonalADN complementarioSecuenciación de nucleótidos de alto rendimientoBCR-ABL1Medical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Bone MarrowMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Clonal EvolutionMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA::DNA, Single-Stranded::DNA, ComplementaryMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide SequencingMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Benzamides::Imatinib MesylateMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::MutationMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Lymphoid::Precursor Cell Lymphoblastic Leukemia-LymphomaMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Oncogene Proteins::Proto-Oncogene Proteins::Proto-Oncogene Proteins c-bcrMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrenceresearch article28451802open access10.1007/s00277-017-3002-11432-0584