title: Two consecutive immunophenotypic switches in a child with immunogenotypically stable acute leukaemia.
abstract: A 12-year-old girl presented with a CD33+ precursor B-acute lymphoblastic leukaemia (ALL) and seemed to respond well to ALL treatment. However, 2 weeks after diagnosis her leucocyte count rose rapidly with a predominance of myeloid blasts with M5b morphology and CD19+ myeloid immunophenotype. Acute myeloid leukaemia (AML) treatment was started and remission was achieved after one course of chemotherapy; the AML treatment was continued for 6 months. Two months after cessation of chemotherapy, the patient developed a bone marrow relapse, this time with an undifferentiated blast morphology and a precursor B immunophenotype. Molecular analysis of the immunoglobulin and T-cell receptor genes showed several clonal gene rearrangements at diagnosis: two IGH, two IGK and two TCRD gene rearrangements. All rearrangements were also detected during the AML phase of the disease, suggesting a phenotypic shift of the same leukaemia. At relapse, 8 months later, all rearrangements were preserved except for one TCRD (Vdelta2-Ddelta3) rearrangement. The first phenotypic shift in the genotypically stable leukaemia was remarkably fast. The most probable explanation for our observations is an oncogenic event in an undifferentiated haematopoietic progenitor clone, with a highly versatile phenotype.
authors.affiliation: Department of Haematology and Stem Cell Transplantation, University Medical Centre, Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands. m.bierings@wkz.azu.nl
authors.forename: M
authors.initials: M
authors.lastname: Bierings
authors.forename: T
authors.initials: T
authors.lastname: Szczepański
authors.forename: E R
authors.initials: ER
authors.lastname: van Wering
authors.forename: M J
authors.initials: MJ
authors.lastname: Willemse
authors.forename: A W
authors.initials: AW
authors.lastname: Langerak
authors.forename: T
authors.initials: T
authors.lastname: Révész
authors.forename: J J
authors.initials: JJ
authors.lastname: van Dongen
mesh_terms: D000208:Acute Disease; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015139:Blotting, Southern; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000276:immunology; D002648:Child; D005260:Female; D015321:Gene Rearrangement; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000276:immunology; D063268:Sialic Acid Binding Ig-like Lectin 3
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3