title: Little evidence for clonal evolution of malignant haematopoietic cells following relapse after autologous bone marrow transplantation.
abstract: By screening for immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements in bone marrow samples aspirated at different time points during the course of disease from 43 patients with acute leukaemia we have analysed the extent of clonal evolution after autologous bone marrow transplantation (ABMT) and addressed the issue of whether the Southern Blot method has the power to reveal clonal proliferations representing minimal residual disease (MRD) in the autologous bone marrow grafts. Our results show that no clonal proliferations were detectable in any of the 43 bone marrow grafts analysed, even after we analysed DNA preparations in 5 cases from cells highly enriched for cells of the original malignant immunophenotype. Moreover, as judged by the Ig- and TCR gene configurations in 11 patients, relapse arose from the original clone even though minor clonal variations did occur in about half of the relapsing patients. We conclude that while the Southern Blot method can detect gene receptor rearrangements in the majority of patients with acute leukaemias and high-grade non-Hodgkins lymphomas, it is not useful for predicting relapse after ABMT. On the other hand, it is possible-by employing it-to evaluate whether or not relapse after ABMT arises from the original malignant clone and to what extent clonal evolution has taken place.
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Aarhus, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Jørgensen
authors.forename: P
authors.initials: P
authors.lastname: Hokland
authors.forename: A W
authors.initials: AW
authors.lastname: Jensen
authors.forename: M
authors.initials: M
authors.lastname: Hokland
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015139:Blotting, Southern; D016026:Bone Marrow Transplantation; D002648:Child; D002999:Clone Cells / Q000473:pathology*; D005260:Female; D015321:Gene Rearrangement; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D012008:Recurrence; D014182:Transplantation, Autologous