title: Emerging BCR/ABL1 Mutations Under Treatment with Tyrosine Kinase Inhibitors in Paediatric Acute Lymphoblastic Leukaemia.
abstract: We report on the emergence and clinical relevance of an unusual BCR-ABL1 kinase domain mutational status in a 2-year-old female with p210-BCR-ABL Philadelphia chromosome-positive acute lymphoblastic leukaemia. We detected three BCR-ABL1 clones determined by the presence of the E255V, D276G and F317L mutations. We point out the usefulness of searching for mutated populations that survive tyrosine-kinase inhibitor therapy and the role of their clonal selection over time in relation to therapeutic intervention.
authors.affiliation: Paediatric Haematology Section, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Agueda
authors.initials: A
authors.lastname: Molinos-Quintana
authors.forename: Virginia
authors.initials: V
authors.lastname: Aquino
authors.forename: Isabel
authors.initials: I
authors.lastname: Montero
authors.forename: Concepción
authors.initials: C
authors.lastname: Pérez-de Soto
authors.forename: Raúl
authors.initials: R
authors.lastname: García-Lozano
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Pérez-Simón
authors.forename: José María
authors.initials: JM
authors.lastname: Pérez-Hurtado
mesh_terms: D019943:Amino Acid Substitution; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002675:Child, Preschool; D002999:Clone Cells; D003131:Combined Modality Therapy; D016903:Drug Monitoring; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D017809:Fatal Outcome; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017710:Lymphocyte Transfusion; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012008:Recurrence; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents; C581634:BCR-ABL1 fusion protein, human; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl