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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
Authors:Tam Constantine S  Otero-Palacios Joselle  Abruzzo Lynne V  Jorgensen Jeffrey L  Ferrajoli Alessandra  Wierda William G  Lerner Susan  O'Brien Susan  Keating Michael J
Affiliation:Department of Leukemia, The University of Texas MD Anderson Cancer Center;, and Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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.
Keywords:rituximab    cytogenetics    fluorescent in-situ hybridization    flow cytometry    immunotherapy
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