title: Subjects with chronic lymphocytic leukaemia-like B-cell clones with stereotyped B-cell receptors frequently show MDS-associated phenotypes on myeloid cells.
abstract: An increasing body of evidence suggests the potential occurrence of antigen encounter by the cell of origin in chronic lymphocytic leukaemia (CLL) and CLL-like monoclonal B-cell lymphocytosis (MBL). However, the scenario in which this event might occur remains unknown. In order to gain insight into this scenario we investigated the molecular, cytogenetic and haematological features of 223 CLL-like (n = 84) and CLL (n = 139) clones with stereotyped (n = 32) versus non-stereotyped (n = 191) immunoglobulin heavy chain variable region (IGHV) amino acid sequences. Overall, stereotyped CLL-like MBL and CLL clones showed a unique IGHV profile, associated with higher IGHV1 and lower IGHV3 gene family usage (P = 0·03), longer IGHV complementary determining region 3 (HCDR3) sequences (P = 0·007) and unmutated IGHV (P < 0·001) versus non-stereotyped clones. Whilst the overall size of the stereotyped B-cell clones in peripheral blood did not appear to be associated with the CLL-related cytogenetic profile of B-cells (P > 0·05), it did show a significant association with the presence of myelodysplastic syndrome (MDS)-associated immunophenotypes on peripheral blood neutrophils and/or monocytes (P = 0·01). Altogether our results point to the potential involvement of different selection forces in the expansion of stereotyped vs. non-stereotyped CLL and CLL-like MBL clones, the former being potentially favoured by an underlying altered haematopoiesis.
authors.affiliation: Department of Medicine and Cytometry Service, Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca (USAL), Salamanca, Spain.
authors.forename: Arancha
authors.initials: A
authors.lastname: Rodríguez-Caballero
authors.forename: Ana
authors.initials: A
authors.lastname: Henriques
authors.forename: Ignacio
authors.initials: I
authors.lastname: Criado
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Sergio
authors.initials: S
authors.lastname: Matarraz
authors.forename: Antonio
authors.initials: A
authors.lastname: López
authors.forename: Ana
authors.initials: A
authors.lastname: Balanzategui
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Wendy G
authors.initials: WG
authors.lastname: Nieto
authors.forename: Emília
authors.initials: E
authors.lastname: Cortesão
authors.forename: Artur
authors.initials: A
authors.lastname: Paiva
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002999:Clone Cells; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000276:immunology* / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism
chemical_list: D011947:Receptors, Antigen, B-Cell
keywords: chronic lymphocytic leukaemia; cytogenetic profile; monoclonal B-cell lymphocytosis; myelodysplastic syndrome immunophenotype; stereotyped IGHV amino acid sequences