title: Chronic lymphocytic leukaemia CD20 expression is dependent on the genetic subtype: a study of quantitative flow cytometry and fluorescent in-situ hybridization in 510 patients.
abstract: CD20 is an important therapeutic target in chronic lymphocytic leukaemia (CLL). In order to examine the relationship between CD20 expression and cytogenetic abnormalities, we correlated the fluorescent in-situ hybridization (FISH) genetic subtype of 510 treatment-naïve patients with CD20 expression as measured by quantitative flow cytometry. Patients were classified using the Dohner hierarchial classification. The median numbers of CD20 antigen sites by FISH subtypes were: 17p- (n = 26), 9341 per cell; 11q- (n = 42), 5886 per cell; +12 (n = 93), 23 603 per cell; negative FISH (n = 153), 8828 per cell; and 13q- (n = 196), 10 781 per cell. Compared to cases with negative FISH, 11q- cases had significantly lower CD20 expression (P = 0.001), and +12 cases had significantly higher CD20 expression (P < 0.001). The significance of trisomy 12 and high CD20 expression was maintained after multivariate analysis accounting for other disease characteristics. Fifty-nine patients received the combination of rituximab and granulocyte-macrophage colony-stimulating factor as frontline therapy; responses were observed in 13 of 14 (93%) patients with +12, in two of four (50%) patients with 11q-, and in 30 of 41 (73%) patients with negative FISH, 13q- or 17p- CLL. Leukemic CD20 expression differed significantly between FISH subtypes. Patients with trisomy 12 CLL showed strong leukemic cell CD20 expression and had a high rate of response to rituximab-based therapy.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Tam
authors.forename: Joselle
authors.initials: J
authors.lastname: Otero-Palacios
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Jorgensen
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.forename: Susan
authors.initials: S
authors.lastname: Lerner
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000097:blood*; D000951:Antigens, Neoplasm / Q000097:blood*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D002869:Chromosome Aberrations; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000069283:Rituximab