title: Change in IgHV Mutational Status of CLL Suggests Origin From Multiple Clones.
abstract: Fluorescence in situ hybridization and immunoglobulin (Ig) heavy-chain variable-region (IgHV) mutational status are used to predict outcome in chronic lymphocytic leukemia (CLL). Although DNA aberrations change over time, IgHV sequences and mutational status are considered stable.
  
  
  
  In a retrospective review, 409 CLL patients, between 2008 and 2015, had IgHV analysis: 56 patients had multiple analyses performed. Seven patients' IgHV results changed: 2 from unmutated to mutated and 5 from mutated to unmutated IgHV sequence.
  
  
  
  Three concurrently changed their variable heavy-chain sequence. Secondary to allelic exclusion, 2 of the new variable heavy chains produced were biologically nonplausible.
  
  
  
  The existence of these new nonplausible heavy-chain variable regions suggests either the CLL cancer stem-cell maintains the ability to rearrange a previously silenced IgH allele or more likely that the cancer stem-cell produced at least 2 subclones, suggesting that the CLL cancer stem cell exists before the process of allelic exclusion occurs.
authors.affiliation: Departments of Oncology and Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
authors.forename: Afaf
authors.initials: A
authors.lastname: Osman
authors.affiliation: Departments of Oncology and Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Gocke
authors.affiliation: Departments of Oncology and Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD. Electronic address: Dgladst1@jhmi.edu.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Gladstone
mesh_terms: D000483:Alleles; D002999:Clone Cells / Q000378:metabolism*; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region
keywords: CLL; CLL Genetics; Cancer stem cell; IGHV